Current methods of transdermal drug delivery have found success using pulsed lasers.  However, pulsed lasers have been very expensive in the marketplace and have resulted in some treatment options to be cost prohibitive.  Therefore, the healthcare industry has been looking for a low-cost alternative to pulsed lasers to expand the list of treatable pathologies.                                (more...)

Available for licensing are patent rights in a method of increasing the number of collagen crosslinks in tissue, thereby strengthening the tissue, potentially preventing damage and improving mechanical properties of the collagen. (more...)

A method of reducing, delaying, preventing, and/or inhibiting the progression of a Cryptococcus infection into the central nervous system and a method for delivery of therapeutic agents to the central nervous system. (more...)

bFGF is an important protein that has many commercial applications due in part to its involvement in numerous physiological functions including embryonic development, angiogenesis, tissue and bone regeneration, development/maintenance of the nervous system, stem cell renewal, and wound repair. The clinical use of bFGF has been hindered due to the instability and rapid degradation of the protein. Novel polymer conjugates of bFGF that retain biological activity and stability under stressors show promising use for a range of applications that include, but are not limited to, wound healing, cardioprotection, bone regrowth, neuronal repair, stem cell self renewal, as well as use as a reagent in laboratory settings.      (more...)

Stapled peptide technology utilizes chemical bonds to constrain peptides into α-helical conformations and results in an extension of potency due to increased resistance to proteases as well as greater cell permeability and bioactivity by the protein. Thus, stapled peptides have emerged as promising therapeutic candidates for treating a variety of human diseases.  Numerous studies have been carried out to develop bioactive-stapled peptides. Among them, there are ring closing metathesis (RCM), azide-alkyne Huisgen cycloaddition (CuAAC), alkylation of cysteine, and lactam bridge formation. However, the RCM and CuAAC methods are very expensive and the latter two methods are generally low efficiency reactions. To address these problems, UCLA researchers have developed an alternative approach to producing stapled peptides that of very low cost and high efficiency. (more...)

Ovarian cancer is the fifth most common cancer in women and the leading cause of death among gynecological malignancies. It was reported that 21,880 women were diagnosed with ovarian cancer and 13,850 died from this disease in 2010 in the United States alone, and overall 5-year survival rate from 1999 to 2006 was 45.6%. The standard systemic treatment for advanced ovarian cancer is combination chemotherapy, using platinum-based drugs such as cisplatin coupled with paclitaxel. Because conventional chemotherapeutic agents target rapidly dividing cells including normal white blood cells, gastrointestinal epithelial cells and hair follicle cells as well as cancer cells, significant side effects are common. In addition, chemoresistance often occurs, leading to death of the patients. Therefore, there is an urgent need to develop targeted systemic therapies.     (more...)

New catalytic processes for the synthesis of enantiomerically pure heterocyclic compounds. (more...)

The K2P potassium ion channel, TREK-1, exhibits widespread expression and carries out key functions in the brain and somatosensory neurons. TREK-1 functionality has been implicated in a number of human diseases and is an attractive therapeutic target. Selective opening of TREK-1 potassium channels limits the firing activity of neurons. Therefore, activation of TREK-1 could be useful in the treatment of pain and depression as well as in neuroprotection from ischemic injury and decompression sickness. TREK-1 is also involved in modulating anesthesia response. Despite the many roles of TREK-1 potassium channels in mediating cellular activities, no specific agonists of TREK-1 are known.The global pain and depression management markets are expected to reach $60 billion by 2015. Available therapeutics often have undesirable side effects, therefore the growing market demands safer, highly specific pharmacological solutions. In addition, neuropathic pain typically fails to respond adequately to conventional analgesics.  A specific activator would be an ideal tool to explore the immense pharmacological potential of TREK-1. (more...)

For decades, scientists have observed that the TfR is highly overexpressed on cancer cells, making them an attractive target for antibody therapy. One observes this correlation in numerous forms of cancer, including breast, lung, colorectal, liver, and bladder cancer, in addition to lymphomas, leukemias, and myelomas.  Potential antibody therapeutics are typically vetted for in-vitro cytotoxicity towards cancer cells before moving into clinical trials. Yet, despite years of effort by researchers in labs around the world, there has been just one published anti-TfR Phase I clinical trial, from 1995. Worse still, it failed to exhibit anti-tumor effects in the study. Despite the continuing development of new anti-TfR antibodies, there have been no additional publications of any clinical trials and the standard evaluation of potential efficacy in vivo continues to be a test of in vitro cytotoxicity. (more...)

Breast cancer is the most common type of cancer that occurs in women in the US and ranks as the second leading cause of cancer death after lung cancer. Of the 230,480 invasive breast cancer cases diagnosed in the US in 2011, approximately 15-20% were "triple negative breast cancer" (TNBC), a subtype of breast cancer that lacks clinical expression of estrogen receptor-alpha (ERα), progesterone receptor, and HER-2 receptors. TNBC tends to occur often in younger and African American women, and it is associated with high proliferative rates, and poor survival. Despite initial responsiveness to some types of chemotherapy, TNBC often recurs early with distant metastases. Treatment of TNBC has also been hindered by its insensitivity to widely-used targeted therapies including trastuzumab, lapatinib, tamoxifen, and aromatase inhibitors. Due to the aggressive nature of TNBC, it accounts for nearly half of all breast cancer deaths. Therefore, there is an urgent need to develop new and more effective therapies for this deadly subtype of breast cancer. The use of novel metformin analogues detailed below may present a promising new treatment for TNBC. (more...)

Stem cell based musculoskeletal tissue-engineering presents the unique opportunity to repair or replace dysfunctional cells in degenerating tissue. In this context, one goal of tissue engineering is to propagate stem cells that can then be reintroduced into the degenerating tissue to repair or replace dysfunctional cells, restore the physical and biochemical properties of the tissue, and re-establish normal function. In particular, mesenchymal stem cells (MSC) are useful in the treatment of musculoskeletal degenerative conditions such as degenerative disc disease and osteoarthritis.  MSCs are abundant, relatively easy to isolate, and can differentiate into a variety of cell types. However, the ischemic and inflammatory environment characteristic of injured tissues proves hostile for the direct introduction of MSCs, which often do not survive in this setting. While growth factors are commonly used to pre-differentiate MSCs into chondrocytes prior to their use, this can cause terminal differentiation and cell hypertrophy that leads to inferior extracellular matrix material properties. Instead, pellet culture systems are better suited for tissue engineering because they can mimic certain embryonic microenvironments that stimulate stable cell differentiation and better support the regenerative process.     (more...)

Trauma to the central nervous system, for example spinal cord injury, can result in a reduction in the quality of life. Methods for improving nerve regeneration after injury or nerve transplantation are needed for improved patient outcome. Also, life expectancy is increasing world-wide leading to a growing ageing population and age-related disorders such as neurodegenerative diseases. Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer’s Disease and Parkinson’s Disease negatively impact quality of life. There is a need for therapeutics for treating neurodegenerative diseases. The global neurodegenerative therapeutics market is growing with a total neurodegenerative disease market predicted to be greater than $23 billion by 2017. (more...)

Stem cell therapy holds the promise of treating a variety of human conditions such as diabetes, cancer, and neurological diseases. It is thought that stem cells could be especially useful for neurological diseases and disorders as the brain has a limited capacity for self-repair and regeneration. There are no effective long-term treatments or cures for certain brain disorders or neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Collectively, these conditions represent a significant unmet medical need. Regenerative approaches for the brain have the potential to address the cause of the disease, rather than simply addressing symptoms, by repairing or reversing the disease state. In addition, cancer relapse has recently been attributed to the existence of cancer stem cells, which are resistant to traditional therapies, exist in numbers too small for detection, and have the potential to develop into new tumors. Treatments that target cancer stem cells would represent a great advance in the field of cancer medicine, and significantly improve prognosis and quality of life for patients by preventing relapse and metastasis. (more...)

Exposed collagen in injured blood vessels provides a substrate for platelets to adhere and aggregate, initiating the first step in thrombosis, the formation of blood clots inside a blood vessel.  Although platelets play an essential role in vascular injury, excessive platelet aggregation may also result in thrombotic disease such as stroke and heart attack. (more...)

This invention provides microRNA therapeutics that augment blood vessel growth, which may have application for indications where it is desired to reduce or stimulate angiogenesis. Reducing or inhibiting angiogenesis may be useful for indications such as degenerative eye diseases and cancer. Stimulating blood vessel growth may be useful for treating indications such as cardiovascular, thrombotic or ischemic diseases. Cells lining blood vessels are usually among the least proliferative cell types, but this desired quiescence may be interrupted in response to growth factors during pathological neovascularization manifested in disease states such as macular degeneration and cancer. MicroRNAs are known to be key regulators of angiogenesis and specific miRNAs have been found to be effective toward these indications. (more...)

Lentiviral vector and method to pre-select/sort anti-HIV gene transduced cells prior to clinical transplantation. (more...)

Sulfatases are a family of enzymes that release sulfate from a range of substrates (steroids, glycoproteins, sulfolipids and proteoglycans). Heparin sulfate proteoglycans (HSPG’s) are present on the outside of most animal cells and are major elements of the extracellular matrix. With their ability to bind to protein ligands, including growth factors, growth factor receptors, cytokines, proteases, lipases, matrix proteins and cell adhesion molecules, HSPG’s are involved in a host of cell signaling and structural functions. Sulfatase-1 (Sulf-1) and sulfatase-2 (Sulf-2) are sulfatases that modify the sulfation status of HSPG’s and thereby regulate a number of critical cell signaling pathways. The dysregulation of sulfatases is observed in many cancers with Sulf-2 in particular being implicated as a driver of carcinogenesis in non small cell lung cancer (NSCLC), pancreatic cancer and hepatocellular carcinoma (HCC). Sulf-2 has been implicated as a cancer causing gene and could be a novel target for new therapeutic strategies. (more...)

Ras proteins are GTPases that have been characterized as proto-oncogenes, which play fundamental roles in human malignancies.  Detected in about 33% of all human cancers, the three major Ras isoforms show the highest frequency of mutation of any oncogene, with K-Ras as the most common.  Though much effort has been invested in trying to find potent small molecule inhibitors of Ras, there has been no reported success.  In fact, Ras has been deemed “undruggable” since the approaches that target Ras function directly seem to yield no efficacy.  Nevertheless, the constitutive signaling induced by oncogenic Ras mutations that sustain cancers remains a serious problem.  Therefore, there is a need to find alternative approaches for directing the search for therapeutic compounds for K-Ras mutant cancers.   (more...)

Prion diseases are a class of neurodegenerative disorders associated with the accumulation of an infectious isoform of a normally innocuous soluble host prion protein (PrPC). In prion disease, the endogenous alpha-helix rich PrPC protein is converted by an unknown mechanism into a protease-resistant and β-sheet–rich PrPSc form. This conversion can occur spontaneously, result from inherited mutations in the PrPC gene, or be triggered by infection with exogenous PrPSc. Animal prion diseases include Bovine Spongiform Encephalopathy (BSE), Chronic Wasting Disease (CWD), and Scrapie, while human prion diseases include Creutzfeldt-Jakob disease (CJD), kuru, and Gerstmann-Sträussler-Scheinker syndrome. Prion diseases are invariably fatal, and no viable treatments are currently available for these devastating disorders. (more...)

Heparin and Low Molecular Weight Heparin (LMWH) are widely used anticoagulants, drugs which prevent blood clotting. However, they have the risk of potentially serious bleeding side effects. Protamine is currently the only approved drug used to reverse the action of heparin, and there is no approved reversing agent for LMWH. However, there are serious potential side effects associated with protamine. UCR researchers have demonstrated significant binding affinity in two synthetic peptide analogues of the HIP heparin-binding domain. Both peptide analogues have been found to be equally effective in neutralizing heparin activity using the Coatest heparin in vitro assay. Fig. Ball and stick model of s9-mer docked to heparin, shown in molecular surface format. For heparin, the sulfur atoms are shown in yellow, the oxygens are shown in red and the carbons are shown in white.   (more...)

Atrial fibrilation (AF) is the most common cardiac arrhythmia and in the U.S. alone affects up to 9% of people over the age of 75. AF can result in blood clot formation and patients have a 7-fold higher risk of stroke. Current approaches to treat AF include (i) the use of anti-arrhythmia drugs that block ion channels in the heart and (ii) electronic ablation of the atrioventricular node and implantation of a defibrillator or pacemaker. Despite these treatments, recurrence is common. In addition, identification of alternative therapeutics has been hindered by the fact that the molecular mechanisms causing AF have remained largely unknown. (more...)

Vesamicol derivatives with anticholinergic properties called "spirovesamicols", which are spirofused piperidines. (more...)

A series of potent inhibitors of vesicular acetylcholine transport. (more...)

Down Syndrome (aka Trisomy-21), which affects approximately one of every 700 babies born in the United States each year, is characterized by varying degrees of stunted cognitive and physical ability as well as characteristic facial and body features. The extent to which an individual will be able to integrate into society is determined by the severity of the condition as well as the timing and extent of intervention. Historically, intervention has included screening with subsequent dedicated therapy and training. However, recent work on the etiology of Down Syndrome (see Lu et al., below) has suggested that inhibition of a chromosome 21 (HSA21)-associated, oligodendrocyte transcription factor (OLIG2) may blunt the effects of over-expression of a subset of HSA21 genes that inhibit the growth of neural progenitors, which are necessary for normal brain development. This approach provides new hope for a prevalent disease with a tremendous burden on society and for which no medical treatment exists. (more...)

Hypertension affects about one in three adults in the United States. Hypertension increases risk of serious health issues, including heart attack, stroke and kidney failure. Approaches to manage hypertension may vary by individual and with differing success. Medications are available, but not all medications are suitable for all patients. Accordingly, new anti-hypertension medications may benefit patients. There are proteins known to reduce blood pressure when administered, however, some proteins are not suitable therapeutics due to short half-life in the body. Improving stability of suitable anti-hypertensive peptides may provide novel therapeutics to lower blood pressure. (more...)

Acyl-COA: cholesterol acyl transferases or ACAT is an enzyme that catalyzes the esterification of cholesterol to form cholesteryl ester. Minimally, ACAT-mediated formation of cholesteryl ester from cholesterol prevents the toxic accumulation of excess cholesterol in a cell and maintains a free diffusion gradient across the cell membrane, particularly in the small intestine. In addition, the assembly and secretion of Apolipoprotein-B containing lipoproteins in the liver and intestines is thought to be dependent on the ACAT-mediated formation of cholesteryl esters from cholesterol. In steroidogenic tissue such as the adrenal glands, ACAT activity produces cytosolic droplets loaded with cholesteryl esters from which they can be mobilized as cholesterol substrates for the generations of steroids. Furthermore, macrophages that accumulate cholesteryl ester in cytosolic lipid droplets as a result of ACAT activity appear foamy and are a characteristic early indicator of atherosclerotic lesions. Animal models that completely lack ACAT protein are viable, albeit with tissue-specific reductions in cholesteryl ester, suggesting that another ACAT enzyme is present in these animals. (more...)

Available for licensing are patent rights in a method of creating nanostructured membranes with topographic features that closely mimic the topographic environment of a variety of basement membranes found in the body. These membranes therefore can provide a means for controlling a number of important cell behaviors. (more...)

Unlike infection by bacteria, persistent viral infections, such as hepatitis C virus (HCV) and human immune deficiency virus (HIV), can remain present through the course of a patient's life. Persistent viruses coexist within the host cell and suppress the immune system, thus perpetuating long term viral presence. Current therapies for HIV provide management of the viral load but are not curative, with patients resigned to a life-long regimen of multiple drugs such as nucleoside reverse transcriptase inhibitors and protease inhibitors, which have numerous side-effects. Patients with HCV undergo lengthy courses of anti-viral treatments that also have significant side effects and are frequently ineffective. A clear need remains for therapeutic alternatives that achieve complete clearance of these and other persistent viruses. (more...)

Opioid receptors are abundant in the central and peripheral nervous system and are the targets of both opiate drugs and a family of endogenous opioid peptides. Seminal work carried out by Dr. Evans' research group at UCLA on this receptor has led to key insights in the field of neuropharmacology. To date, the delta opioid receptor has been implicated in various diseases including, but not limited to, pain, depression, neuroprotection, drug abuse and impulse control disorders. Moreover, on-going work has hinted at additional roles for this critical receptor. A method for screening potential modulators of the delta opioid receptors would provide unparalleled insight into the development of targeted therapies against this key target. (more...)

The branched-chain alpha-keto acid dehydrogenase complex catalyses the rate-limiting step in the oxidation of BCAAs (branched-chain amino acids). Scientists at the University of California, San Diego have discovered evidence to suggest that some forms of autism and epilepsy might be treatable with dietary supplementation. Specifically, this technology identifies a correlation between a specific mutation among some autistic patients and reduced levels of certain amino acids. It is anticipated that this technology could provide a basis for testing of patients with autism and/or epilepsy for mutations in the relevant gene, which could be commercialized or licensed to a genetic testing company. It is anticipated that treatments, either dietary supplementation or small molecule therapeutics, could be developed. (more...)

Exposure to organophosphates (OP) from both pesticides and nerve agents leads to inhibition of acetylcholinesterase (AChE), resulting in a build-up of acetylcholine in the body, and potentially death.   The only OP stoichiometric bioscavenger in use today is butyrylcholinesterase (hBChE). Human butylcholinesterase (hBChE) specifically and efficiently captures offending OP molecules in the circulation of exposed individuals, sequestering the OP as an inactive conjugate in the plasma. However, due to ~ 500-fold molecular mass of BChE molecules compared to nerve agent OP molecules, very large amounts of highly purified BChE protein have to be used for effective protection resulting in a greater potential for toxicity and prohibitively high costs of treatment, thus restricting its application to very small number of exposed individuals. hAChE's monomeric structure and reduced glycosylation compared to the tetrameric hBChE standard provides a simpler protein for effective protection from OP-poisoning. In addition, point mutations introduced by UCSD researchers to hAChE enhance its efficiency as a bioscavenger. For example, the Y337A mutation confers greater resistance to permanent catalytic incapacitation by dealkylation (aging) upon covalent OP inhibition, and the F338A mutation increases the reactivation rate of OP-inhibited AChE. (more...)

Exposure to organophosphates (OP) from both pesticides and nerve agents leads to inhibition of acetylcholinesterase (AChE), resulting in a build-up of acetylcholine in the body, and potentially death. Human butyrylcholinesterase (hBChE) specifically and efficiently captures offending OP molecules in the circulation of exposed individuals, sequestering the OP as an inactive conjugate in the plasma. The combination can be used as a stoichiometric antidote. However, due to ~ 500-fold molecular mass of BChE molecules compared to nerve agent OP molecules, very large amounts of highly purified BChE protein have to be used for effective protection resulting in prohibitively high costs of treatment, thus restricting its application to very small number of exposed individuals. (more...)

Adipose stem cells (ASCs) can be used for the treatment of diabetes, insulin resistance, and obesity.  These cells can also be administered to increase the amount of brown fat thermogenesis (e.g., for treating obesity).  Mesenchymal stem cells (MSC) therapies are being developed for treatment of inflammatory, metabolic, cardiovascular, and degenerative diseases.  Both ASC- and MSC-based therapies are being developed for treating cancer, cardiovascular disease, acute lung failure, stimulation of tissue regeneration (e.g., skin, heart, and liver) and other degenerative and inflammatory conditions.  Currently, there are no established means for expanding ASCs or MSCs in vitro for extended periods of time in a non-differentiated state. (more...)

Anthracyclines are the most commonly prescribed chemotherapeutic agent for their effectiveness in treating cancer.  However use of anthracyclines can have the severe, adverse effect of cardiac toxicity leading to cardiomyopathy and clinical heart failure.  Currently available medications to counteract anthracycline-induced cardiotoxicity either do so at the cost of anti-tumor activity, or there is insufficient clinical trial data to support their efficacy in preventing cardiotoxicity.  Thus widespread use of these compounds is limited.    There is a clinical need for a pharmaceutical compound that can prevent and/or treat the cardiac side effects of anthracyclines while maintaining their anti-tumor activity. (more...)

Researchers at the University of California, Irvine have found a new use for a known compound for treatment of fatty liver disease which has been shown to be effective in animal studies. (more...)

Fluorescence tomography (FT) is a sensitive but intrinsically low spatial resolution imaging modality due to strong photon scattering in biological tissue. Recently, a temperature-responsive fluorescence contrast agent has been reported using ICG loaded pluronic nanocapsules. The temperature dependence of these contrast agents provides a major opportunity to overcome the spatial resolution of regular FT by using temperature modulation/tagging.Researchers at the University of California, Irvine have developed a new molecular optical imaging modality termed “temperature-modulated fluorescence tomography (TM-FT)” that can provide high resolution images without sacrificing the exceptional sensitivity of fluorescence-based detection. TM-FT is based on the temperature modulation of fluorescence quantum efficiency in a highly scattering medium. The medium is irradiated by both excitation light and a high intensity focused ultrasound (HIFU) wave. The crucial benefit of HIFU is that the temperature of the medium is modulated with a very high spatial resolution (~1.5 mm) due to the absorption of acoustic power in the ultrasound focal zone. When the temperature sensitive fluorescence agent presents within HIFU focal zone, the local temperature increases and in turn, changes the fluorescence quantum efficiency inside the focal zone. As a result, the emitted fluorescence light intensity and lifetime have detectable change only when the agent is present within the focal zone. In other words, it allows fluorescence reconstruction with high spatial resolution by scanning focused ultrasound column over the medium while detecting the change in fluorescence signal. Using a proper reconstruction algorithm, this technique can also provide quantitatively accurate fluorescence images. Finally, the temperature sensitive agents can be modified to target molecular pathways and processes associated with many diseases and hence, TM-FT technique can provide a suitable platform for true molecular in vivo imaging. (more...)

Researchers at UCLA have developed small molecule inhibitors of Ca2+-Release-Activated-Ca2+ (CRAC) channels that are crucial for the activation of immune cells. CRAC channels mediate the Ca2+ influx that is necessary for short- and long-term responses by immune cells. Through screening of a large chemical library, the researchers have identified a leading compound and multiple analogs that block Ca2+ entry into T-cells. The IC50 value of the lead compound blocking T-cell Ca2+ entry is 195 nM. Testing in an animal model of autoimmune disease, experimental autoimmune encephalomyelitis (EAE), demonstrated that the lead CRAC channel inhibitor could significantly reduce T-cell infiltration into the central nervous system, the disease target tissue, and reduce the overall severity of disease. The findings present promising application of these compounds to treating transplant rejection and numerous autoimmune diseases, not limited to: Rheumatoid arthritis Multiple Sclerosis Type I Diabetes Inflammatory Bowel Disease (more...)

Researchers at the University of California, Davis have discovered that inhibition of a key regulatory protein can prevent acute post injury cellular responses leading to cartilage degradation and osteoarthritis.   (more...)

Squamous cell carcinoma (SCC) is one of the most commonly diagnosed cutaneous cancers and affects over 250,000 people each year. The current diagnostic standard uses hematoxylin-eosin (HE) staining of tissue sections; however, this approach does reliably distinguish SCC from other skin conditions, including pseudoepitheliomatous hyperplasia (PEH). Even though the pathogenesis of these skin conditions is dissimilar, SCC and PEH can look virtually identical upon clinical and histological examination. Small tissue sample sizes, dense inflammation, and poor orientation add to the difficulty of distinguishing between these conditions with histological examination alone. Thus, a robust genetic test for accurately distinguishing between SCC and PEH will provide improved diagnoses and treatment for patients. (more...)

Researchers at the University of California, Davis have discovered that pharmaceutical targeting of galentin-12 may prove beneficial by both reducing adiposity and improviing insulin sensitivity. (more...)

COMP is an essential extracellular matrix protein that forms a “molecular bridge” between extracellular matrix components and provides a structure on which to bind.  The modular structure of COMP acts as a scaffold aggregating multiple growth factors and presenting them to the cell surface. In addition to binding multiple TGF-β1 molecules, COMP contains additional binding sites for growth factors and cytokines, including members of the VEGF, FGF, and HGF families. COMP’s cell surface binding properties bring the aggregate complex of COMP and associated growth factors to the cell surface preventing diffusion of the growth factors, increasing the physiological relevance of the signaling, especially where multiple signals are required, and ultimately increasing the growth-related transcription within the cell. (more...)

Epilepsy, a brain disorder in which a person has repeated seizures over time, can severely affect a person’s quality of life. The onset of the epileptic seizures generally begins between the ages of 5 and 20, although the condition can strike people at any age. Epilepsy is generally a lifelong condition that may require surgery or medication. In general, there is no known way to prevent epilepsy. New methods for the prevention and therapy for epilepsy and other neurological disorders will be very useful for those that are currently suffering or may suffer from these debilitating disorders.Researchers at the University of California, Irvine have developed a new method for the prevention and therapy for epilepsy and other neurological disorders. This method can be used to prevent the onset of epilepsy caused by insults (i.e., bodily injury, irritation, or trauma). (more...)

Available for licensing are patent rights to a method for removal of antigens from tissues, thereby lessening the immune response when those tissues are utilized in a host, for example, as xenogeneic implants. (more...)

A novel hydrolytically degradable polyethylene glycol derivative for use in pharmaceutical and cosmetic formulations. (more...)

Influenza has been the cause of yearly epidemics and global pandemics throughout history. Due to the high degree of sequence conservation between disease genes in humans and flies, Drosophila has been enlisted to serve as a powerful multicellular host model to identify novel interactions between viral proteins and host machinery. Among influenza's eleven viral genes, NS1 (nonstructural protein 1) is known to be indispensable for virulence. There are very few effective drugs to treat influenza infection and these drugs (e.g., Tamiflu) act on highly mutable extracellular proteins that function in the late phase of viral escape from the cell. Also, viral surface proteins which are the main targets for vaccines mutate rapidly to evade suppression. Knowledge of new host signaling responses to viral infection could lead to therapies targeted to these interactions. These treatments may be effective at suppressing the pathogenesis of many different strains of flu unlike vaccines which typically target only a few strains and require constant reformulation since the virus can evade host antibodies. (more...)

Among all solid organ or tissue transplantations, corneal transplantation is the most successful, with a 2-year survival rate of 90% in patients with inflamed and avascular (low-risk) graft beds.  Unfortunately, the rejection rate reaches as high as 50-90% when the grafting is performed on inflamed and highly vascularized (high-risk) corneas. Many patients who are blind as a result of corneal diseases fall in this category after traumatic, inflammatory, infectious, or chemical damage. Such patients are not considered as good candidates for transplantation surgery and have to give up their hope for vision restoration. To address these challenges, investigators at University of California at Berkeley have developed a technical strategy using a combined blockade of VEGFR-3 and VLA-1 that markedly improves high-risk corneal transplant transparency and survival. This strategy suppresses lymphatic vessels in grafted corneas. It provides a new and powerful strategy to combat high-risk corneal transplant rejection. The strategy may also be used to treat low-risk transplant rejection and other immune-or lymphatic-related diseases. It can be locally or systemically administered. (more...)

Taken as a whole, roughly half of patients receiving treatment for invasive cancer die. Conventional radiation and chemotherapies have largely failed in improving survival and, since they are non-specific, often result in multiple adverse side effects. Immuno-based cancer treatment offers the possibility of higher specificity, but current therapies are limited in their effectiveness. Immunomodulators, including the EGFR antibody (Erbitux), can eliminate differentiated tumors but are ineffective in removing cancer stem cells and therefore do not fully eradicate the disease. T cell-mediated immunotherapies require an antigen that is both highly expressed and restricted to the tumor, so they are effective in only a small subset of cancers. In contrast to T cells, NK cells do not recognize foreign antigens, but rather detect changes in self-molecules displayed at the surface of autologous cells. NK cells can recognize and kill cancer stem cells, but are often inactivated in cancer patients. Methods to induce the NK-mediated killing of cancer cells, specifically cancer stem cells, could provide new therapies in the treatment of cancer. (more...)

Targeted radiation therapy has been a mainstay of treatment for human cancers for decades. The development of compounds that sensitize malignancies to radiation has significantly enhanced its efficacy. The ability of "radio-sensitizer" compounds to improve therapy is dependent on their entry into cancerous cells. However, the toxic effects of most radio-sensitizing compounds on the body limit their administration to patients. Therefore, there is a great need to develop novel compounds or delivery systems that boost the uptake of radio-sensitizing compounds into tumors. Improved uptake of radio-sensitizing compounds into tumors could drastically improve the response to therapy and reduce the duration of treatment. Persistent viral infections have enormous global health and economic impacts. There are nearly 5 million new HIV infections every year and more than 1 in 6 Americans is infected with HSV. The highly adaptive nature of these viruses allows drug resistance to develop against targeted therapy. These drug-resistant properties necessitate therapies that target multiple, independent mechanisms involved in viral infection, replication, and transmission. There is an obvious need to develop novel drugs that inhibit viral infection and reduce the amount of virus in a patient. Reducing viral propagation through targeted-inhibition of multiple mechanisms would have an enormous impact in reducing the viral infectivity and transmission of patients. (more...)

The Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system.  One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants.  Therefore, scientists are searching for a general surrogate marker that could be used to target any HIV-infected cell regardless of its mutational status, enabling eradication of the virus. In this regard, scientists at UCSF have recently begun to take a closer look at Human Endogenous Retroviruses (HERVs) that are present in all human cells.  HERVs are a family of retroviruses found in the human genome and are thought to have originated from an ancient retrovirus that become permanently integrated with the DNA of its host's germ cells.  HERV viruses are inactive in normal cells but one type of HERV, HERV-K, is activated in HIV-infected cells.  The HERV-K proteins are presented on the surface of HIV-infected cells.  Because HERV-K is expressed in all HIV-infected cells, it is thought HERV-K antigens presented on the surface could be a good candidate to generally target any HIV+ cell. (more...)

Researchers at the University of California, Davis campus have discovered a novel metabolic pathway in human breast and propose this pathway as a new paradigm in molecular etiology of breast cancer. (more...)

Transition metal-catalyzed amination reactions are amongst the most powerful methods available for accessing the carbon nitrogen based motifs ubiquitously found in medicinal agents and natural products. Recently, efforts have focused on the amination of classically “inert” simple phenolic derivatives to synthesize these structures more readily. Towards this goal, a number of groups have searched for alternative phenol based amination partners, which can be used to direct the assembly of functional groups onto an aromatic ring. Resulting polysubstituted aryl amine motifs are commonly encountered in drug scaffolds, naturally occurring small molecules, pesticides, ligands for catalysis, and materials chemistry. Given the ubiquity of carbon-nitrogen bonds in medicinal agents, more efficient and cost-effective cross-coupling reactions will provide significant economic advantages to therapeutic development and manufacturing. (more...)

It is estimated that 1 in 6 men will be diagnosed with prostate cancer in their lifetime. One of the consequences of removing the prostate for prostate cancer is a non-permanent injury of the cavernosal nerve during open radical prostatectomy (RP) or robot-assisted radical prostatectomy (RARP), which may result in post-operative sexual dysfunction. These sexual side effects can severely affect the quality of life for men and their loved ones. Researchers at the University of California, Irvine have developed a new use for an existing compound that can be used to prevent, mitigate, or treat erectile dysfunction associated with prostate removal surgery. (more...)

New use for Sorafenib as a p21 inhibitor for cancer treatment (more...)

THE SCREEN  Dr. Stephen Smale, Professor and Vice Chair of Microbiology, Immunology & Molecular Genetics at UCLA and colleagues have developed an improved cell-based screen for the identification of selective modulators of pro-inflammatory gene expression. The technology utilizes a macrophage cell line derived from either transgenic mice or differentiation of genetically modified embryonic stem cells. The resultant cell line contain two types of reporters, which allow small molecules that selectivity inhibit transcription of the inflammatory gene of interest to be accurately and easily separated from those that inhibit inflammatory gene expression more broadly. The technology is a significant improvement over conventional reporter gene assays that utilize cell lines stably transfected with a promoter-reporter gene plasmid containing a green fluorescent protein (GFP) or luciferase reporter gene. The stably integrated plasmids in these conventional reporter assays do not assemble into native chromatin and therefore do not behave in the same manner as an endogenous gene, resulting in erroneous screening results. The methodology developed by Dr. Smale and colleagues allows the same low cost, rapid and sensitive screening afforded by the conventional reported gene assays, but with the significant advantage that gene expression is measured in a native chromatin environment. This permits the identification of small molecules that are far more likely to modulate gene expression in vivo and be suitable for further development. A second major advantage of the methodology is offered by the inclusion of a second reporter cassette that allows non-selective inhibitors to be identified and excluded. Dr. Smale has initially developed and validated the screen using a bacterial artificial chromosome (BAC) for the IL12B gene, but the approach could readily be modified to screen for modulators of other genes of interest. THE INHIBITORS  A variety of existing and new small molecule inhibitors of IL12B transcription were identified using this approach, and were further validated using a primary cell assay. IL12B encodes the p40 subunit of the IL-12 and IL-23 cytokines; the p40 protein is the target of the Stelara antibody, a highly effective new therapy for the treatment of psoriasis and possibly other inflammatory diseases. The new compounds identified in the screens could be further developed into drugs to treat a variety of inflammatory conditions including inflammatory bowel disease, atherosclerosis, psoriasis and sepsis. Selective small molecules would have added advantages over antibody-based therapeutics of cheaper production, greater tissue biodistribution and the potential for oral administration. (more...)

Hematopoietic stem cell transplantation (HSCT) is a mainstay of treatment for many hereditary disorders and lymphatic and blood cancers. However, HSCT regimens are maligned with poor transplantation efficiency and patient complications. For instance, the toxic side effects associated with chemotherapy or radiation-mediated pre-conditioning can compromise patient survival. In addition, the poor rate of transplanted cell engraftment and insufficient supplies of donor cells has limited the use and efficacy of HSCT. Therefore, there is an urgent need to improve the efficiency of engraftment and lower the toxicity of preconditioning regimens. Advancing these phases of HSCT will improve patient outcomes by reducing risks from preconditioning, overall durations of treatment, and costs from extended hospitalization and multiple transplantations. (more...)

Compounds that are useful as anti-inflammatory agents. (more...)

Molecular imaging of cancer has the potential to facilitate early detection and to provide a more detailed assessment of disease and tumor margin.  Molecular imaging probes have been heralded by the FDA Critical Path Initiative as tools to increase the speed and cost-effectiveness of clinical trials for cancer therapies.  However, imaging probes currently in use in the clinic are limited by a lack of specificity and/or sensitivity or are limited to a small subset of cancers.  Therefore, new molecular imaging probes with more broad applications to cancer are needed. (more...)

There are more than 23 million patients with type-2 diabetes in the U.S. and ~18 million of those might have as much as 50% higher risk than a non-diabetic to develop Alzheimer's disease (AD).  The increased AD risk factor is also true for the ~51 million patients in the U.S. who are obese at midlife.  No new drugs to battle AD have been approved by the U.S. FDA since 2003 and the few medications currently available only address cognitive loss symptoms, with some patients having no relief of symptoms at all.  It is also believed that none of the medications currently available can either delay or modify disease progression.  UC Davis researchers believe that a major problem in understanding the AD pathology and in improving the treatment is the lack of early biomarkers to signal potential risk and provide insight into disease progression.  Finding efficient biomarkers can improve diagnosis and help target drugs to the right pathological processes at the right time.  (more...)

The market for new therapeutic products that will combat resistant strains of infectious pathogens commands $26 billion annually.  The U.S. market share for new generation antibiotics alone is expected to reach $10 billion this year.  To overcome the growing problem of microbial resistance, drug development companies have adopted a number of strategies based on the production of beta-lactamases, including developing new beta-lactamase inhibitors that can be co-administered with beta-lactam antibiotics.  This particular strategy has yielded three beta-lactamase inhibitors are all active against most class A enzymes, such as TEM-1, but not against class C enzymes, like AmpC.  Also, these inhibitors afford no protection to cephalsoporins clinically and have never been combined, for example, with the 3rd generation cephalosporins, leaving these widely used drugs susceptible to the evolution of the extended spectrun beta-lactamases (ESBLs).  Thus there is pressing need for new inhibitors that can be combined with a primary beta-lactam, especially a cephalosporin, rescuing these first-line antibiotics for continued clinical utility. (more...)

A potentially valuable therapeutic strategy for preventing HIV infection or preventing the spread of the virus within an infected individual is to inhibit viral entry into human cells. Since HIV entry requires interactions between human cell surface proteins (notably CD4, CCR5, and CXCR4) and HIV envelope proteins (gp120 and gp41), compounds that bind to one or more of these proteins are being explored as candidates for blocking HIV entry. However, many of the compounds tested so far are active only against particular HIV strains, can be expensive and difficult to produce, or require exceedingly high concentrations to be efficacious in practical microbiocidal formulations. Thus, there is a pressing need to find new HIV entry inhibitors that can overcome these problems. (more...)

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Bioactive peptides and peptidic small molecules are of interest as potential intracellular therapeutics in human disease. Peptide therapeutics have great potential for high target specificity, low toxicity, and low accumulation in tissues. Unfortunately natural unmodified peptides often exhibit poor permeability across cell membranes and this has limited the utility of peptides as therapeutics for intracellular targets.  (more...)

Currently, no malaria vaccines are available for clinical use. The need for a vaccine is also compounded by the emergence of multiple drug-resistant Plasmodium strains. In 2008, there were nearly 250 million cases of malaria and one million deaths worldwide according to the World Health Organization. Moreover, in addition to chloroquine resistance, resistance to newer anti-malarials is growing. Thus, innovative vaccines and anti-malarials are needed to reduce the morbidity and mortality caused by malaria infections in humans. (more...)

Approximately 45% of normal adults snore at least occasionally, and 25% snore habitually. Snoring not only adversely affects the health of the snorer, but it is exceptionally disruptive of the sleep patterns of their partners. In addition, 2-4% of adults suffer from obstructive sleep apnea, which is a disorder of repetitive upper airway collapse and is particularly common in middle-aged and older males and in postmenopausal females with an incidence of 4-6%. Current treatments for snoring and/or obstructive sleep apnea are limited. The most effective interventions for sleep apnea are expensive machines providing continuous airway pressure requiring wearing a face mask during sleep, intrusive dental appliances, and surgical procedures. Due to the invasive nature of these procedures and their side effects, treatment compliance is low. (more...)

Epilepsy is a debilitating disease of the central nervous system, which can cause severe seizures. Affecting around 1% of the population, this disease requires prolonged, and often life-long, drug treatments. Keppra, or Levetiracetam, is an important anti-convulsant drug used to treat seizures in patients with epilepsy. Keppra's patent rights in the US expired in 2009 opening up a large opportunity for generic production of the drug. Drug synthesis can be costly, however, due to laborious and expensive syntheses of starting materials. The ability to renewably produce the chiral-specific starting materials from simple molecules in bacteria could greatly reduce production costs. (more...)

The rise of community- and hospital-acquired methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for new antibiotics. More than 90,000 Americans acquire potentially deadly MRSA infections each year, which annually are estimated to kill more people than AIDS in the United States. Proteins displayed on the surface of S. aureus play key roles in the infection process as they promote bacterial adhesion to host cells and tissue, acquire essential nutrients and circumvent the immune response. Most surface proteins in S. aureus are attached to the cell wall by the Sortase A (SrtA) enzyme. Thus, sortase enzymes are a universal target for therapeutic agents against Gram-positive bacteria. (more...)

 The progesterone receptor (PR) is required for several aspects of mammalian female reproduction. PR null mice have overlapping defects that preclude an understanding of its multiple functions in ovulation, pregnancy, mammary gland biology, and sexual behavior. Researchers at UCLA have generated a PR conditional excision (PRCE) allele in which loxP sites flank exon 1. Homozygous PRCE females are fertile and appear to be functionally normal. Global cre mediated excision of the floxed exon 1 using EIIa-cre mice resulted in systemic loss of exon 1 and PR protein. Female mice homozygous for this null allele were sterile, as expected for PR knockout (PRKO) females. Conditional loss of PR will facilitate investigation of the spatial and temporal roles of PR in both normal development and disease. (more...)

Myocardial infarction (heart attack) affects millions of people in the United States each year. New and more effective therapies for myocardial infarction are in urgent demand. Currently, there are a few treatments available for myocardial infarction. However, these treatments do have undesirable consequences. Drug-eluting stents are often used after angioplasty, which works acutely but often lead to restenosis. Stem cell therapy is theoretically less toxic and adequately repairs damaged heart muscles, but its mechanisms are unclear and does not always work. Other treatments may help reduce heart load or inhibit processes such as thrombosis and pulmonary edema, but are not directly helpful in reducing infarct size. (more...)

A system using nanotechnology to synthetically replicate the body's immune function for uses in body fluid filtration, stimulation of immune system, therapeutics and diagnostics. (more...)

A novel method for the production of emulsions and dispersions, directed to methods for the formation of colloidal suspensions. These suspensions are formed with or without mechanical action and without surfactants, polymers, or stabilizing agents. (more...)

  Background Over a dozen companies have pursued the development of TGF- β modulators for the treatment of cancer, pulmonary fibrosis, and renal disease. However, the near-ubiquitous presence of the three mammalian TGF- β isoforms across tissue types, as well as its complex and diverse effects on downstream signaling pathways, mean there is a high likelihood that chronic global suppression of TGF-β will result in undesirable off-target effects. An agent effecting tissue and disease-specific mitigation of TGF- β activity while sparing much of its contribution to normal cellular function would be of extremely high therapeutic value for a wide range of inflammatory, fibrotic and neoplastic diseases.   The integrin family of cell surface receptors are emerging as promising targets for tissue type-selective modulation of TGF- β. Because TGF- β activation in a given tissue type requires association with a specific integrin, it is believed that targeting such interactions will lead to effective therapeutics while avoiding many of the possible systemic effects of indiscriminate TGF- β suppression. In mice, conditional deletion of avb8 blocks airway inflammation and fibrosis in COPD and asthma models and can completely inhibit experimental autoimmune encephalitis. In human biospecimens, activation of TGF- β by avb8 has been directly implicated in both fibrotic and inflammatory processes of the airway in COPD.  Until now, no chemical, small molecule, or high affinity antibody agent was available that selectively blocks the interaction of TGF- β and integrin avb8.                                                                            Description UCSF investigators have developed the first mouse anti-human neutralizing monoclonal antibody that prevents the binding of two TGF- β isoforms to integrin avb8. This is the sole agent of any type that selectively targets these associations, without which TGF-b activation in vivo is severely compromised. UCSF investigators have characterized the target epitope of the antibody. In vivo, this antibody blocks airway inflammation in transgenic mice expressing only human and not mouse avb8. Short-term safety tests show no deleterious effects using high-concentrations of the antibody (7mg/kg). Animal model safety and additional efficacy tests are underway in humanized mice expressing human avb8.   This antibody offers several distinct advantages over current TGF- β modulators. First, the antibody only inhibits the activation of the TGF-b1 and b3 isoforms, sparing the neutralization of TGF-b2. The TGF-b1 isoform is widely considered to account for the majority of the disease-related biology of TGF-b.  Second, the specificity for cells expressing only the avb8 integrin isoform decreases off-target effects such as autoimmune responses, rapid-onset atherosclerosis, and carcinoma development. Third, the antibody selectively disrupts the binding of TGF- β to avb8 in a way that does not influence general cell adhesion properties mediated by this interaction, further minimizing non-TGF-b-related effects. (more...)

A novel system and methods that provides efficient display and screening of peptide libraries at the cell surface, and enables rapid and quantitative characterization of the candidate peptides. (more...)

RNA viruses such as the hepatitis C virus (HCV) often quickly develop strains that evade host immune responses and vaccines and develop resistance to antiviral drugs. While both immunity and the efficacy of many antiviral drugs depend heavily on the specific features of the viruses, the high mutation rates occurring in these viruses (associated with the error-prone viral replication) increases the variability of such features and therefore facilitates the rapid emergence of resistant viral strains. With approximately 200 million people worldwide infected by HCV, including 35,000 to 185,000 new cases each year and 10,000 to 20,000 fatalities each year in the United States, overcoming the obstacles to effective drug therapies due to HCV's high mutation rates is a high priority. However, prior to this invention there has been no effective means for defeating new resistant strains other than to continually develop new drugs or to administer high concentrations of combinatorial drugs. There are no anti-HCV vaccines. (more...)

Researchers at the University of California Davis have developed and tested novel compounds useful for treating Osteoporosis, promoting bone fracture healing, and improving pro-engraftment of stem cells to bone.  (more...)

The population of the US is aging and among the many age-related changes that occur is the change in speech. Addressing this change in the vocal folds, and thus the voice, has not been successful to date. Researchers at UCI have developed a minimally invasive technique to address this issue. (more...)

UCSF researchers have created new small molecule activators of executioner procaspases 3, 6 and 7 and initiator caspase 9. These compounds have been shown to activate the relevant caspase targets in vitro and to induce apoptosis in a p53 deficient cell line. In addition, a coupled screening assay has been developed which can identify compounds that activate the executioner procaspases in the presence of caspase 9. (more...)

The invention provides a method to identify women subjects with symptoms of menopausal transition who will benefit from hormone replacement therapy. (more...)

Chemokines are a group of homologous yet functionally divergent proteins that mediate leukocyte migration and activation and play a role in regulating angiogenesis. Secondary lymphoid organ chemokine (SLC, also referred to as Exodus-2 or 6Ckine) is a chemokine expressed by high endothelial venules in T-cell zones of spleen and lymph nodes. It strongly attracts nave T-cells and mature dendritic cells to the initial site of immune activation. (more...)

While considerable progress has been made towards the diagnosis and treatment of a plethora of cancers, very few inroads have been made with respect to pancreatic cancer. As the 5th leading cause of cancer-related deaths in the U.S. it is among the most devastating. Indeed, pancreatic cancer is difficult to diagnose, is largely untreatable and is highly metastatic. Thus the need for sufficient technology with which to combat the disease is self-evident. Unfortunately current clinical protocols for the diagnosis and treatment of pancreatic cancer have been met with little, if any, success. (more...)

Various diseases of iron metabolism are caused by abnormal hepcidin production, either too much or too little. In the case of anemia of inflammation, the production of hepcidin is stimulated by various cytokines including IL-6. Increased hepcidin levels cause the loss of ferroportin from the surfaces of macrophages engaged in the recycling of iron from senescent red cells. As a result, iron is trapped in macrophages and blood iron concentration decreases, restricting the flow of iron to the bone marrow, and thus slowing the production of hemoglobin and consequently decreasing the production of erythrocytes. In another iron metabolism disease, juvenile hemochromatosis (JH), the decreased expression of hepcidin, is the result of the mutations in the HJV gene. The decreased expression of hepcidin results in severe iron overload. (more...)

Emulsions comprised of microscale droplets of a liquid in another immiscible liquid are common products and have been made for centuries. These emulsions can be simply made by applying viscous stresses using a mechanical mixer that break larger droplets into smaller droplets, consequently storing energy in the additional droplet interfacial area that is created. Traditional mechanical mixing devices can achieve droplet diameters to around 200 nm, but usually have difficulty creating droplets smaller than this limit. Existing methods for making elastic emulsions of small droplets typically alter the composition to raise the volume fraction of the dispersed (i.e. droplet) phase up to the point where the droplets begin to pack and deform. Due to the geometrical nature of the packing of disordered spheres, a significant elasticity appears at droplet volume fractions above sixty percent, and is reached by adding more of the dispersed phase while mixing. Obtaining elastic emulsions at droplet volume fractions much below sixty percent has never been achieved simply by the history of applied flow stresses. (more...)

Systemic lupus erythematosus (SLE or lupus) is a disease characterized by the production of autoantibodies that react with native cells and tissues, causing inflammation, pain, and damage throughout the body. Increased production of IgG in SLE causes the precipitation of immune complexes in the kidney, resulting in irreversible renal damage and failure. There is no known definitive cure for SLE, and treatment is relegated to symptomatic relief of inflammation flare-ups and to non-antigen specific immunosuppression. Non-steroidal anti-inflammatory drugs and anti-malarials are used to treat milder forms of SLE, though corticosteroids and immunosuppressants are used in more severe cases. However, the efficacy of immunomodulating drugs is limited by the increased risk of infection in lupus patients, while corticosteroid therapy is also limited by its side effects, such as obesity, diabetes, and osteoporosis. There is an estimated 1.5 to 2 million Americans with lupus who will benefit from therapeutics that intervene at the gene product level and interrupt the pathogenic process. (more...)

Conventional chemotherapy, currently used in the treatment of cancer is not capable of differentiating between cancer cells and any other cell types with elevated metabolism. Therefore, normal tissue toxicity is the limiting factor of non-specific chemotherapeutics. To avoid destruction of normal cells, targeted cancer therapeutics are delivered specifically at the tumor site, where they exert their cytotoxic effect. Targeting is achieved via recognition of a specific tumor antigen that is abundantly expressed by the tumor cells and either completely absent or present in miniscule amounts in normal tissues. Successful targeting of a tumor antigen is a function of both specificity and affinity; however the serum pharmacokinetics (PK) of the agent defines its bioavailability and ability to achieve maximum anti-tumor effect. Furthermore, PK is crucial in molecular imaging applications, where the tumor targeting molecule may be a carrier of a positron or gamma emitting radionuclide (PET, SPECT), or a paramagnetic agent (MRI). The PK profile of the carrier molecule controls how early suitable contrast is achieved, in order to differentiate the disease from the general background. It is important to note that the optimal PK for therapy is not suitable for imaging and vice versa. Therefore, it is absolutely advantageous to be able to control the PK of targeted anti-tumor drugs and diagnostics for achieving maximum tumor killing and acquiring unambiguous images, respectively. (more...)

The host immune system is crucial to final resolution of viral infection. Unfortunately, many viruses, such as HIV-1 and hepatitis C virus (HCV), can evade the immune system. There is no pharmaceutical treatment that can eradicate these viruses from infected individuals. The fate of these infected individuals hinges on the findings of new therapeutic approaches, which has been a long-standing goal of HIV/AIDS research. (more...)

Estrogens and estrogen receptor alpha ligand treatments are promising treatments to prevent neurodegeneration in the central nervous system due to diseases such as multiple sclerosis (MS), Alzheimers disease, Parkinsons disease, spinal cord injury, stroke, etc. Although these treatments are both anti-inflammatory and neuroprotective, many individuals cannot tolerate long durations of treatment. Their intolerance stems from the induction of breast cancer and uterine cancer, each of which are mediated by estrogen receptor alpha in the breast and uterus, respectively. Therefore, there is a need for a treatment that is both neuroprotective and non-cancer inducing. (more...)

Systemic lupus erythematosus is a disease characterized by the production of autoantibodies that react with native cells and tissues, causing inflammation, pain, and damage throughout the body. Increased production of autoantibodies causes immune complex deposition in the kidney, which can result in irreversible renal damage and failure. Edratide, a peptide drug in Phase II clinical trials, is injected subcutaneously in patients to help induce regulatory and suppressive T cells which both downregulate autoimmune responses. Now, however, UCLA investigators are able to orally administer the D form of the peptide. (more...)

The worldwide antiviral market is estimated to grow from ~$18 billion to as much as $25 billion by 2011. Recognizing the expanding range of biological threats and the limited resources available to address each individual threat, the NIAID has recommended a shift in basic research from the "one bug-one drug" approach toward a more flexible, broad-spectrum approach that can reduce the time and cost of creating new antiviral products. Viruses can be generally divided into two main categories: lipid-enveloped or non-enveloped. Enveloped viruses replicate within the host cell, recruit their components to the cell membrane, then bud from and utilize that membrane, essentially, as a vehicle to transport virus to the next uninfected cell. The lipid membrane of enveloped viruses, although derived from the host cell, differs in several biophysical properties and lacks the ability to repair damage, thus representing a susceptible target for broad-spectrum antivirals. (more...)

The number of people with diabetes continues to increase in the United States. The medical complications associated with diabetes are very serious. Diabetes is the leading cause of blindness, kidney failure, and limb amputation, and a major contributor to cardiovascular disease mortality. Current tests for diabetes include the Fasting Plasma Glucose (FPG) test and Oral Glucose Tolerance Test (OGTT). These tests are time consuming, invasive, require overnight fasting and long seating time, and are not practical for routine screening. In addition, these tests do not provide reliable pre-diabetic screening. Furthermore, although insulin and other drugs exist, many patients suffer adverse effects or become resistant to these drugs over time. Therefore, there is a need for an efficient test that can predict risk for diabetes and to diagnose the disease. Novel methods for the prevention and treatment of type 2 diabetes would also be beneficial. (more...)

Natural killer (NK) cells are a population of lymphocytes believed to play a role in the surveillance of tumor growth and metastasis and in the regulation of hematopoiesis. (more...)

The invention is the discovery of several new forms of secreted IgE. These forms have potential applications in the diagnosis of immediate hypersensitivity-allergic disease. Previously thought to include only one or two forms, UCLA researchers have now determined that circulating IgE is expressed in four different forms. These four specific forms, which primarily differ at their C-terminal ends, are believed to have differential specificities and binding affinities for the cells that cause allergic reactions (mast cells/basophils). Currently, serum tests of allergic antibodies (IgE) measure either total IgE protein or IgE vs. specific allergens, essentially measuring this family of proteins as a single type. By establishing a set of solid phase IgE immunoassays for these different forms of IgE, it should be possible to establish far more accurate diagnostic tests for human IgE-mediated hypersensitivity disorders related to specific allergens such as ragweed, dust mite, etc. (more...)

Prophenins belong to a new class of antimicrobial peptides discovered in mammalian white blood cells. First isolated from porcine leukocytes, prophenins display exceptionally strong endotoxin (LPS) binding activity as well as antimicrobial activity. The potential of prophenins over other LPS-binding peptides and proteins lies in their small size and their simple but unique structure, composed of repeating decameric elements. In vitro experiments indicate that prophenins have over 60 times greater affinity for LPS than polymyxin B sulfate. Thus, these peptides show promise as a new class of potent antibiotics for gram-negative bacterial infections.The term prophenin derives from its composition, which is rich in proline (~50%) and phenylalanine (~20%). The protein sequence consists of repeating proline-rich decamers. Binding assays indicate that even an individual decamer subunit has LPS-binding activity at least equivalent to that of polymyxin B. In vitro results show that the LPS-binding properties of the holoprotein are more than the sum of its parts, but even the parts show enough anti-LPS activity to make them potentially useful antibiotics. (more...)

Rationale: geranylgeranylation of Ras proteins is a key escape pathway for oncogenic cells treated with farnesyl transferase inhibitors (FTIs). Small molecule antagonists of GGTaseI are therefore promising candidates for fully blocking activation of Ras.Leads: Both UC22 and UC23 are drug-like compounds that are likely to be have good oral bioavalability based on their structures and functional groups.In vitro potency: UC22 and UC23 were assayed for their ability to inhibit GGTAase-I geranylgeranylation of RhoA and KRas4B. IC50s are UC22 (0.5 uM RhoA, 0.9 uM KRas4B) and UC23 (0.3 uM RhoA, 2 uM KRas4B).Specificity: both UC22 and UC23 have been shown to be specific for GGTI versus GGTII and FTICell growth inhibitory potency: UC22 and UC23 were assayed for their ability to inhibit proliferation of human cell lines MDA-MB231 and MiaPaCa2. IC50s are UC22 (50uM in MDA-MB231 and 20 uM MiaPaCa2) and UC23 (10 uM in MDA-MB231 and 8 uM in MiaPaCa2). Cell cycle arrest at the G1 phase was observed in these studies.Target: The molecular target is known and there is SAR and a crystal structure which will aid in further medicinal chemistry. (more...)

Age related decline in immune function represents a critical factor that contributes to the higher incidence of infection and cancer in older human populations. In addition, the demand for improved strategies that facilitate healthier aging is expected to increase as life expectancy continues to rise in many developed nations. It is therefore incumbent that the discovery of molecular pathways that are capable of mitigating the decline of cellular processes caused by aging be used to foster the development of enhanced preventative and therapeutic approaches against diseases of the aged. Nuclear factor erythroid derived 2-related 2 (Nrf2), is a transcriptional activator that has been shown to regulate a plethora of genes responsible for antioxidant activity. While the exact mechanisms that connect the effects of oxidant injury to the decrease in cellular immunity have yet to be elucidated, available evidence does point to an important role of the Nrf2 regulatory pathway in the initiation of proper innate immune responses. Notably, it has been reported that aging is associated with a reduction in Nrf2 activity with a concomitant increase in oxidative stress in mammalian model systems. (more...)

Endocytosis is an essential process in living cells that ensures proper regulation of the surface expression of membrane receptors and enzymes. This process is generally regulated by specific sequence motif in the cytoplasmic tail of internalizing proteins. The two major internalization motifs reported are tyrosine-based and di-leucine-based signals.  Prostate specific membrane antigen (PSMA), a potential therapeutic target and diagnostic marker, has been the subject of immense investigation due to its selective expression in human prostate cancer cells. Furthermore, PSMA over-expression is implicated in high-trade cancers and solid tumor formation. (more...)

With the rapid advances of modern pharmacology, effective drugs have been discovered for many diseases; however, most of those drugs have undesirable side effects due to their inability to distinguish between diseased and healthy cells. For instance, chemotherapy that is commonly used for treatment of cancer does not only target the cancer cells, but also damages healthy cells. (more...)

Resin-based and resin-containing materials are routinely used in dental practices as direct filling materials, fissure sealing agents, and as bonding resins or resin cements for metal, porcelain, and resin inlays, veneers, crowns, and bridges. The use of resin-based materials will likely continue to increase in the future.While the use of resin-containing materials is beneficial to the appearance of patients, these materials carry the risks of cytotoxicity and allergy. Most dental bonding technologies use primers containing the hydrophilic resins HEMA or TEGDMA. HEMA and TEGDMA have been shown to be a cause of these adverse effects due to the release of unpolymerized monomers in the surrounding tooth area, thereby triggering apoptosis or programmed cell death. Similarly, the adverse effects of bleaching agents on dental pulp and gingivae are well established. Therefore, methods for neutralizing the harmful effects of resin monomers and bleaching agents would be beneficial to current dental practices. (more...)

The only currently available TB vaccine, an attenuated Mycobacterium bovis strain Bacille Calmette-Guerin (BCG), is of variable efficacy. A large carefully conducted meta-analysis has estimated the potency of BCG to be approximately 50%. UCLA researchers developed and reported in the last several years a recombinant BCG expressing the Mycobacterium tuberculosis 30 kDa major secretory protein (r30). This vaccine, named rBCG30, induces greater protection than BCG against aerosol challenge with a highly virulent strain of M. tuberculosis.Immunocompromised individuals, such as HIV infected persons, are more susceptible to TB, and HIV infection significantly increases TB mortality. BCG has been used to vaccinate immunocompromised persons; however the live BCG vaccine can disseminate in an immunocompromised host and cause serious illness and even death. Therefore a safer TB vaccine is desired for immunocompromised individuals. (more...)

Polymeric vesicles are a new class of nanoscale self-assembled materials that show great promise in drug delivery applications. Compared to liposomes, polypeptide vesicles have increased stability and can respond to external stimuli. (more...)

Vaults are recently discovered large cellular particles made of proteins and unique small RNA. Vaults are present in large quantities in all eukaryotic cells and are thought to mediate transport between the nucleus and the cytoplasm. The size and symmetry of vaults is similar to the transporter of the nuclear pore complex (NPC) with which it is thought to interact. Very recently a high correlation between the overexpression of vaults and multi-drug resistance to chemotherapy has been established.UCLA researchers propose a method of generally knocking out the vault function thought to be associated with multi-drug resistance by targeting vault RNA with antisense. They have been successful in targeting and destroying the vault RNA in vitro and are currently testing this method in tissue culture cells. (more...)

Strokes are the most common life-threatening neurological disease, and are the third leading cause of death in developed countries after heart disease and cancer. Approximately 6-8 percent of all strokes results from non-traumatic subarachnoid hemorrhage, a condition where blood leaks from the cerebral vasculature into the subarachnoid space. About 8 percent of subarachnoid hemorrhages result from rupture of an intracranial aneurysm. Ruptured intracranial aneurysms are associated with a high rate of mortality. Approximately 15% of the patients die soon after the initial rupture. An additional 20 to 30% of the patients die during the first 2 weeks following the initial rupture. Rebleeding is one of the major causes of death in the patients who survive the initial hemorrhage. In addition to the high mortality rate associated with ruptured intracranial aneurysms, there is also a high morbidity rate among patients who survive the rupture long term. Almost two-thirds of patients well enough to be discharged home after surgical obliteration of the aneurysm have a residual neurological deficit. (more...)

Mycobacterium tuberculosis is one of the worlds most important pathogens. It infects 2 billion people worldwide and causes 8 million new cases of pulmonary tuberculosis and 3 million deaths annually. Indeed, tuberculosis is the worlds leading cause of death from a single infectious agent. The rising incidence of tuberculosis worldwide in large part is due to the AIDs epidemic and has been accompanied by the emergence of multi-drug-resistant strains. These factors underscore a serious public health threat and the need to develop novel methods to treat and prevent the disease. (more...)

The prevalence of Insulin-Dependent Diabetes Mellitus (IDDM) in the U.S is 300,000 to 500,000 individuals of all ages with 30,000 new cases reported each year. IDDM is an autoimmune disease caused by the destruction of pancreatic beta-cells by the bodys own T-lymphocyte. Current measures to diagnose IDDM require that patients manifest clinical symptoms, which become evident only after a vast majority of beta-cells had been destroyed. Treatment then involves the replacement of the bodys insulin with an exogenuous source, an approach that may lead to complications such as hypoglycemia, local allergic reactions, insulin resistance, and generalized insulin allergy. Importantly, insulin therapy involves life-style adjustment in which patients need to strictly adhere to therapy regimens. An alternative to insulin therapy is the use of immunosuppressants to control the diverse autoreactive T cell population. This strategy of treatment lacks specificity and thus can also interfere with the normal functions of the immune system. (more...)

Signal transducer and activator of transcription proteins (STATs), nuclear factor-κB (NF- κB), and SMA (small body size)- and MAD (mothers against decapentapegic)-related proteins (SMADs) are three key families of transcription factors that are widely used downstream of cytokine-mediated signaling to regulate gene expression. The activity of STATs, NF- κB, and SMADs is tightly regulated at several levels, and inappropriate regulation can result in diseases in humans, including cancers and immune disorders. (more...)

IgA is a polymeric effector molecule of the immune system that mainly acts at mucosal surfaces and is highly resistant to extreme pH conditions, whereas IgG is monomeric and acts in the blood at a narrower pH range. IgG is known for its potent complement activation and, in contrast, IgA is unable to fix complement. Combining the characteristics of IgA and IgG into a single immunoglobulin molecule may produce more effective therapeutic agents. (more...)

UCSF cardiologists have developed a novel topical anesthetic composition that facilitates radial artery cannulation. This composition can be delivered either as a topical cream or through a transdermal patch and can be co-marketed with radial catheterization sheaths and cannulaes to increase product appeal to clinical users. In clinical trials, this novel composition causes local increase of the arterial diamter (by 25% or more for at least 30 minutes) and provides local anesthesia in the patient, without inducing undesirable systemic effects, thus enabling clinicians to insert radial arterial catheters with greater ease, reduce the risk of spasm, and reduce pain experienced by patients undergoing this procedure.  (more...)

UCSF investigators have identified a novel endogenous agent that activates the Aryl Hydrocarbon Receptor. (more...)

UCSD researchers have discovered new synthetic oligodeoxynucleotides (15-mers) useful in treating cancer and certain autoimmune diseases. These compounds induce apoptosis in chronic lymphocytic leukemia cells but actually stimulate normal human B cells. Their mechanism of action does not depend on CpG dinucleotides, and they do not require the addition of cationic lipids or any other adjuvant to exert their effects. (more...)

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In the search for in vitro cell lines that can be continuously cultured, neurons have been amongst the most intractable. This was presaged by their behavior in situ; relative to other tissues, a limited number of cells are reported to divide. Excluding immortalized cell lines, there is a dearth of well-characterized, established cell lines from central nervous system (CNS) and neuronal tissues and those in existence are often limited in their ability to mimic the biology of the primary neurons from which they were originally established. Effective drug discovery screening programs require the use of primary cultures that: are phenotypically representative of the primary cells from which they were derived can be used to generate continuously proliferating cultures of specific neuronal cell lines Cell lines that meet these criteria will prove invaluable for neurobiological studies, CNS drug discovery efforts and may significantly change the landscape for therapeutics. (more...)

The present invention relates to bone conduction hearing and, more particularly, to a device that can deliver sound to the inner ear through the bone by bypassing the ear canal and the middle ear. (more...)

Monoclonal Antibodies Against the Prokaryotic Cyclic Nucleotide-Modulated Ion Channel Mlok1 (more...)

New materials and methods that enable the simple inclusion of 18F into cancer-targeting peptides that can be used as radiolabels for PET imaging (more...)

It is known that oxidized phospholipids are pre-inflammatory and pro-atherogenic and that high-density lipoproteins (HDL)—or its lipoprotein also called apolipoprotein-A—is involved in mediating reverse cholesterol transport. Currently there is no accepted method for high-throughput measurement of reverse cholesterol transport or reverse-oxidized phospholipid transport. (more...)

Parasitic diseases, such as malaria, African sleeping sickness, Chagas disease and trichomoniasis, are major worldwide health problems for which new chemotherapy is desperately needed. For example, an estimated five million cases of the sexually transmitted disease trichomoniasis occur each year in the United States alone. Malaria kills over a million people a year worldwide and is second only to tuberculosis in its impact on world health. Current treatments for these diseases have varying degrees of effectiveness and serious problems with toxicity, drug-resistant strains, and lack of selectivity. Therefore, there is a need for the development of new therapeutics for the treatment of these diseases.Researchers at the University of California, San Francisco have discovered that a novel series of small molecules, in a class that has previously been evaluated for antiviral and anticancer therapy, is effective in killing a variety of parasites, including those that cause malaria, trichomoniasis, Chagas disease and African sleeping sickness. By screening a library of these novel small molecule compounds, the researchers found several promising lead compounds that killed a range of parasites in cell culture assays and had no toxicity in mouse studies. These compounds therefore represent a potentially powerful new therapeutic avenue for parasitic diseases. (more...)

UCSF investigators have discovered the anti-inflammatory effects of two naturally occurring human proteins. (more...)

BACKGROUND:  The regulation of gene expression by transcription factors is a fundamental aspect of the physiology of all cells. The aberrant expression of transcription factors can lead to abnormal development and various diseases, like cancer and heart defects. One disease which might be approached by modulating transcription factor function is acquired immune deficiency syndrome (AIDS), caused by the retrovirus HIV, which incorporates itself into the host cell via reverse transcription of its RNA. Several therapeutics exist currently that target various critical points in the HIV life cycle, however, used alone, these drugs have low effectiveness and cannot prevent the virus from developing resistance to these known agents. Effective new methods of targeting underexploited aspects of the HIV life cycle, such as transcription of the HIV virus, remain desirable.   TECHNOLOGY:  The present invention was conceived as a dominant negative regulator of the Tat transcription factor, thus leading to the inhibition of HIV-1 transcription. More broadly, this application can be used to generate multiple potent dominant negative regulators of transcription by linking a transcription factor to a protein that localizes to the transcriptional machinery. (more...)

A UCSF investigator has developed a novel anti-cancer therapeutic protein that directly targets VEGF expressing tumor cells together with any associated dividing endothelial cells for programmed cell death. By reversing the activity of VEGF from an angiogenic factor to a cell death factor, this novel protein can attack a growing tumor from multiple directions. This would potentially provide a more rapid response and more optimistic prognosis than current treatment methods. Additionally, this protein could be used therapeutically in many other diseases characterized by pathologic angiogenesis. (more...)

Research into modulating immune function through immunostimulatory T cells has been hampered by the lack of identification of the molecular markers on such cells. UCSF investigators have identified a novel endogenous human T cell population that can significantly enhance the proliferative capacity of a T cell response. In contrast to T cells that can be induced to suppress a proliferative response, these are a naturally occurring, functionally mature T-cell subpopulation that induce the proliferation of a T cell. (more...)

Abnormal development of lymphoid tissue plays a critical role in many autoimmune diseases, such as rheumatoid arthritis and Graves disease. In addition, the migration of lymphocytes into diseased lymphoid tissue facilitates the progression of diseases such as AIDS. UCSF researchers have identified a pathway, involved both in the development of lymphoid tissue and in the migration of lymphocytes into lymphoid tissue, which is a potential target for screens for therapeutics to treat these diseases and other immune disorders.The B-lymphocyte chemoattractant (BLC/BCA1), through its interaction with the G-protein coupled receptor BLR1/CXCR5, is important for the migration of B-cells and a subset of T-cells and macrophages into lymphoid follicles. Recent investigation by UCSF researchers has proven that the BLC/BLR1 pathway is essential for B-cell migration to the spleen and lymph nodes, for the development of lymph nodes and Peyers patches, and for the establishment of a positive feedback loop with lymphotoxin Lta1b2 to mediate follicular dendritic development and persistent BLC expression. This work and additional studies at UCSF suggest that the interaction between BLC and its receptor, BLR1/CXCR5, may be a useful target for modulation of the normal and ectopic development of lymphoid tissue as well as lymphocyte migration. (more...)

Stem cell therapy holds the promise of treating a variety of human conditions such as diabetes, cancer, and neurological diseases. It is thought that stem cells could be especially useful for neurological diseases and disorders as the brain has a limited capacity for self-repair and regeneration. Additionally, there are no effective long-term treatments or cures for certain brain disorders or neurodegenerative diseases such as Alzheimers, Parkinsons, and Huntingtons disease. Collectively, these conditions represent a significant unmet medical need. Regenerative approaches for the brain have the potential to address the cause of the disease, rather than simply addressing symptoms, by repairing or reversing the disease state. However, because the underlying causes of the brain diseases are diverse, several different approaches are required to adequately address the various causes. Some examples include cell replacement for dead or lost cells, modification and augmentation of faulty circuitry, and delivery of therapeutics to poorly functioning cells for protection from degeneration. While some cell types and sources have been identified (e.g. fetal porcine ganglionic eminence cells and dopaminergic neurons), their efficacy has not been proven. In addition, questions remain about whether such cells will form brain tumors in vivo, persist for long periods of time, or will work in aged brains, when people are most susceptible to neurological disease. There is a need in the field for the identification of cell types that can be applied in many disease contexts. DESCRIPTION: UCSF Researchers have discovered that a population of neural precursors, called medial ganglionic eminence (MGE cells), possess several advantageous properties that would make them useful for a number of neurological diseases. When injected into various regions of the brain, MGE cells disperse homogenously over long distances, form inhibitory interneurons (GABAergic neurons), integrate to form functional connections with endogenous circuits, and influence the activity of surrounding neurons. Interestingly, MGE cells behave this way in postnatal brains, suggesting they could work in aged brains. By virtue of these qualities, it is thought that MGE cells can be used to treat several brain diseases via cell replacement, modification of endogenous circuitry, or by delivery of therapeutics. To support this assertion, the researchers have performed proof-of-principle experiments in rodent models of epilepsy and Parkinsons disease. Implantation of MGE cells into the cortex of postnatal brains in rodent models of epilepsy was shown to significantly reduce seizure symptoms. MGE cells achieved this via both GABAergic modulation of electrical activity and cellular replacement of inhibitory neurons. Further, implantation of MGE cells into the striatum of 6-OHDA rodents was shown to ameliorate symptoms of Parkinsons disease via modulation of faulty circuitry resulting from degeneration of dopaminergic input. Based on these initial data, the researchers envision that MGE cells could be applied to additional brain disorders. Indeed, preliminary data suggest that MGE cells could be used to treat diseases caused by aberrations in the organization or activity of the brain, such as stroke, cerebral palsy, and Schizophrenia. MGE cells can regulate a process known as experience-dependent plasticity, which allows for changes to be made in the wiring or activity of neurons. Selective reactivation of this process in the adult brain could result in functional reorganization that could fix or compensate for any lack of function and alleviate the symptoms of disease. Preliminary data also suggest that MGE cells can be used to treat spasticity caused by spinal cord injury. It is thought that spasticity results hyperactivity spinal circuitry. MGE cells grafted into the spinal cord are expected to integrate and produce factors that inhibit local circuitry to reduce spasticity. Experimental testing in related animal disease models is underway. (more...)

Researchers at the University of California, Irvine, have created a model of brain aging in cultured brain slices. (more...)

In the pharmaceutical industry, synthetic chemists often alkylate starting compounds to generate compounds that have more desirable properties. However, the current reagents used in this modification process can be expensive or harmful to the chemist. (more...)

Antioxidant and xenobiotic metabolizing enzymes are critical in the protection against chemically induced oxidative/electrophilic stress in cells that cause damage, DNA mutation, apoptosis, and cancer. Transcription of these cytoprotective genes and xenobiotic metabolizing genes is regulated through cis-active sequences known as antioxidant response elements (ARE). Coordinated induction of these genes mediated through the ARE is regulated by a signal transduction system that is still in the process of being fully characterized. Regulation of ARE function is mediated by various basic leucine zipper transcription factors including members of the 'cap n collar' (CNC-bZIP) Nrf1 is a CNC-bZIP protein that regulates the expression of ARE. Previous attempts at developing viable Nrf1 deficient mice were unsuccessful since the Nrf1 gene is necessary for embryonic development. (more...)

The highly abundant GTP binding protein elongation factor Tu (EF-Tu) fulfills multiple roles in bacterial protein biosynthesis. EF-Tu also binds other ligands, including four structurally distinct families of antibiotics. The lack of sequence homology among the identified EF-Tu ligands demonstate promiscuous peptide binding by EF-Tu. (more...)

  Normal 0 0 1 117 672 UC Berkeley 5 1 825 11.1282 0 0 0 This invention consists of a bioengineering and surgical method for the treatment of cardiac injuries by mechanical stabilization of the injured region. The technique involves the injection or implantation of a material into the border zone of the injury or infarct. When implanted, the material will integrate into the host myocardium and share the mechanical loads during the cardiac cycle, reduce the fiber stresses in the infarct zone, and prevent progression to congestive heart failure. In addition the material can be used as a carrier for the addition of transplanted cells for improved rates of healing. The combined effect of matrix-associated reduction in fiber stress and enhanced transplanted cell survival has the potential to be a novel therapy to restore cardiac function and reduce heart failure. (more...)

Nearly one quarter of men worldwide are homozygous for a mutation in a gene that encodes a key sperm surface protein that is critical for normal sperm functioning in the female reproductive tract. Methods of detection of the genetic mutation, or the deficit of the protein on sperm, are predictive of reduced male fertility. Supplementation of sperm with the purified protein restores sperm function.  (more...)

Bromacil Herbicide PAbs Specific polyclonal antibodies for the assay of the herbicide bromacil. OTHER ANTIBODIES: 4-Nitrophenol Biomarker PAbs 1992-742 Specific polyclonal antibodies for the bioassay of the primary metabolite of many organophosphates and nitro-aromatics, substituted 4-nitrophenol. Bacillus Delta Endotoxin PAbs 1992-745 Specific polyclonal antibodies for the assay of the delta endotoxins of Bacillus thuringiensis subsp. kurstaki and Bacillus thuringiensis subsp. israelensis. Pyrethrin Insecticide PAbs 1992-746 Specific polyclonal antibodies for the analysis of natural pyrethrin insecticides and the pyrethroid S-bioallethrin. Bentazon Herbicide PAbs 1992-747 Specific polyclonal antibodies for the assay of the herbicide bentazon and its N-alkylated derivative. Benzoylphenylurea Insecticide PAbs 1992-748 Specific polyclonal antibodies for the assay of the Benzoylphenylurea insecticides (Dimilin, Bay Sir and others) and their related compounds. t-Octylphenyl polyethoxylate ether Pabs 1992-749 Specific polyclonal antibodies for the assay of the Triton-X class of surfactants, t-Octylphenyl polyethoxylate ether). These compounds are widely used as cleansers, detergents and as active ingredients in vaginal contraceptives. Bacillus Beta Exotoxin PAbs 1993-704 Specific polyclonal antibodies for the assay of the beta exotoxin of Bacillus thuringiensis. Triazine Herbicide Pabs 1993-705 Specific polyclonal antibodies for the assay of derivatized triazine herbicides (atrazine, simazine and others). Urea Herbicide Pabs 1993-711 Specific polyclonal antibodies for the assay of phenylurea herbicides (diuron, monuron, linuron). (more...)

Triazine Herbicide Pabs Specific polyclonal antibodies for the assay of derivatized triazine herbicides (atrazine, simazine and others). OTHER ANTIBODIES: 4-Nitrophenol Biomarker PAbs 1992-742 Specific polyclonal antibodies for the bioassay of the primary metabolite of many organophosphates and nitro-aromatics, substituted 4-nitrophenol. Bromacil Herbicide PAbs 1992-743 Specific polyclonal antibodies for the assay of the herbicide bromacil. Bacillus Delta Endotoxin PAbs 1992-745 Specific polyclonal antibodies for the assay of the delta endotoxins of Bacillus thuringiensis subsp. kurstaki and Bacillus thuringiensis subsp. israelensis. Pyrethrin Insecticide PAbs 1992-746 Specific polyclonal antibodies for the analysis of natural pyrethrin insecticides and the pyrethroid S-bioallethrin. Bentazon Herbicide PAbs 1992-747 Specific polyclonal antibodies for the assay of the herbicide bentazon and its N-alkylated derivative. Benzoylphenylurea Insecticide PAbs 1992-748 Specific polyclonal antibodies for the assay of the Benzoylphenylurea insecticides (Dimilin, Bay Sir and others) and their related compounds. t-Octylphenyl polyethoxylate ether Pabs 1992-749 Specific polyclonal antibodies for the assay of the Triton-X class of surfactants, t-Octylphenyl polyethoxylate ether). These compounds are widely used as cleansers, detergents and as active ingredients in vaginal contraceptives. Bacillus Beta Exotoxin PAbs 1993-704 Specific polyclonal antibodies for the assay of the beta exotoxin of Bacillus thuringiensis. Urea Herbicide Pabs 1993-711 Specific polyclonal antibodies for the assay of phenylurea herbicides (diuron, monuron, linuron). (more...)

Lymphoma diagnosis through the identification of specific cell antigen  (more...)

Novel single chain variable fragment (scFV) antibodies against human Mucin-1 (MUC-1) have been developed by researchers at University of California, Davis to diagnose and treat adenocarcinoma cells, such as human breast, prostate and ovarian cancer cells. This method is superior to current methods for optimal diagnosis and treatment of these cancers. For example, while radioimmunotherapy using intact monoclonal antibodies (MoAbs) has been utilized in the treatment of breast cancer and other solid tumors, therapeutic success has been limited by the large size of the MoAb (150 kD) inhibiting blood clearance and retarding accumulation of the radiopharmaceutical at the tumor site(s). This powerful method utilizes small peptide antibodies that are specifically targeted to MUC-1, one of the epithelial mucin family of molecules that has received considerable interest as an antigen target because it is widely expressed on a large number of epithelial cancers and is aberrantly glycosylated, making it structurally and antigenically distinct from that expressed by non-malignant cells. These targeted antibodies make it possible to both image and treat primary and metastatic tumors associated with breast, prostate and ovarian cancer by killing only cancerous cells. New methods using these antibody peptides can be superior to current methods in that: Identification of cancer cells is achieved through anti-MUC-1 peptide antibody binding profiles to select the scFv to the type of cancer by large tissue arrays (eg prostate and breast cancers); and, Targeted therapy to MUC-1 positive cells is possible resulting in the death of only cancerous cells. Targeted imaging (eg PET or SPECT) for sensitive detection and treatment of cancerous cells can be made ideal using these innovative reagents. Efficient cost-effective production of the small cancer-specific peptide antibodies is possible using standard techniques. Focused, hyperimmune libraries of single chain Fvs against the tandem repeat region of the MUC1 antigen upregulated on most epithelial cancers, e.g., prostate, breast, ovarian, etc. Rigorously screened against the antigen and highly characterized tissues from patients with prostate and breast cancers. Screened for relationship to cancer grade; Screened for high affinity; Directly screened using biotinylated discFvs recombinantly engineered using methods in complementary patent pending invention. Evidence for xenograft uptake in mice and not in normal tissues including gastrointestinal tissue. Images Anti-MUC-1 MAb compared to anti-MUC1 scFv E1 and G1 binding to human prostate cancer (grade 3) (A-C) and not to normal human colon (D). A) BrE-3 MAb B) E1 scFv C) G1 scFv and D) G1 scFv on human colon (more...)

Amino Acid and Peptide Conjugates of Amiloride allowing for furnishing inactive prodrugs that can be selectively activated by tissue endopeptidases (more...)

On-bead Screening Process of Neuraminidase Inhibitors (more...)

Mathematical Modeling of Skeletal Muscle Forces and Limb Motions during Functional Electrical Stimulation (more...)

Aβ-binding Small Molecules for Alzheimer's Disease Treatment and Imaging (more...)

Anti-CD22 Monoclonal Antibodies used for the Treatment of Lymphoma and Leukemia (more...)

Method for Cryopreservation of Human Tissue and Cells (more...)

Neural Stem Cells as Therapeutic Agents for the Treatment of Hearing Loss (more...)

In 2007, diabetes accounted for $174 billion in health-care costs, with 20.8 million Americans diagnosed with this disease. Type I diabetes comprises up to 10% of diabetes mellitus cases in North America. Intensive insulin therapy can help reduce the risks of developing complications like neuropathy, nephropathy and ketoacidosis, but it requires three or more insulin injections or use of an external insulin infusion pump. We currently have excellent insulin infusion pumps, and continuous glucose sensors are now sufficiently accurate to be used to regulate insulin delivery. What is missing is a program (algorithm) to regulate insulin delivery based on the signal from a continuous glucose sensor. In addition, the risk of nocturnal hypoglycemia is still high. (more...)

Since 1988, the Food & Drug Administration has required that the enantiomeric composition of all drugs be known, making stereoselective reactions essential for the pharmaceuticals industry. However, the reactions used to establish chirality at one or more stereocenters often are not sufficiently stereoselective to warrant asymmetric synthesis, thus necessitating the addition of costly stereoisomer resolution steps. Chiral pool resolution strategies have two significant limitations that are responsible for the growing popularity of stereoselective syntheses: Isolation of a desired stereoisomer from the chiral pool imposes severe limitations on reaction yield; and Resolution steps often entail the use of environmentally-damaging solvents, which increases costs associated with waste disposal. A significant body of research has shown that it is often possible to increase stereoselectivity in asymmetric reactions using high pressure and thus bypass or minimize costly purification steps; however, high pressure apparatus is infeasible for syntheses on the kilogram scale and above. (more...)

A novel peptide ligation process to prepare native peptide bonds under mild, aqueous, reagent-free conditions, with water and carbon dioxide as the only by-products. (more...)

Scientists at the University of California and the University of Wisconsin working on cell cycle and development research have created a suite of antibodies to important transcriptional regulators.  These antibodies target the following: Histone 2B Phosphorylated Histone 2B TAF1 (Tata Box Binding Protein Associated Factor 1) Ash1 (histone methyl-transferase that methylates Histones 3 and 4) MLL (a DNA-binding protein that methylates histone H3) MDU (Drosophila Set/MBD protein) The following table provides more deatail: Antigen Species Type Reactivity H2B Drosophila Monoclonal (rat) universal H2B-S33P (phospho-group on serine 33) Drosophila Monoclonal (rat) Polyclonal (rabbit) Drosophila Ash1 (epigenetic activator) COOH term Drosophila Monoclonal (rat) Polyclonal (rabbit) Drosophila Ash1 (epigenetic activator) COOH term Drosophila Polyclonal Drosophila TAF1 (coactivator) Drosophila Mono (rat) and polyclonal (rabbit) Drosophila MLL (mammalian epigenetic activator) Mouse Polyclonal (rabbit) Mouse, Human Mdu (Drosophila Set/MBD protein Drosophila Monoclonal (rat) Drosophila (more...)

Chromosome abnormalities are often associated with genetic disorders, degenerative diseases, and cancer. In fact, the deletion or multiplication of copies of whole chromosomes, chromosomal segments, or specific regions of chromosomes are common occurrences in cancer, and can be the cause of some cancers. One such amplified region found in studies of breast and colon cancer cells is on chromosome 20, specifically 20q13.2. Increased copy number of 20q13.2 is found in greater than 25% of cancers of the ovary, colon, head-and-neck, brain, and pancreas. However, it is unknown what gene target(s) is/are responsible for this increase in cancer. (more...)

University of California researchers have developed an antibody fusion protein that functions as a novel cytotoxic drug, though both, the antibody and the non-antibody partner by themselves are not cytotoxic. This fusion protein serves to decrease or eliminate cell proliferation by stopping cell division and causing cell death (apoptosis). In addition, it could be used as a universal delivery system to selectively deliver proteins, nucleic acids, and other chemicals into various kinds of cancer cells. Initial studies have demonstrated promising results using the antibody fusion protein specially against cancer cells of hematopoietic origin such as lymphomas, leukemias, and myelomas. (more...)

Microtubules are dynamic protein tube-shaped polymers that are essential for normal cellular activities including cell division, various kinds of cell motility, and intracellular signal transduction. Microtubules are in dynamic equilibrium with their soluble protein subunits, alpha and beta tubulin heterodimers. The dynamics of microtubules are critical for their functions. Various diseases and disorders are associated with microtubule assembly, disassembly, and/or function, including diseases and disorders associated with cell proliferation such as cancer, neurodegenerative diseases such as Alzheimer's, atherosclerosis, and restenosis. Several powerful agents that affect microtubules are known, some of which destabilize or disassemble microtubules, and others such as taxol, which promote the formation of microtubules. Most of the agents affect the normal dynamic behaviors of the microtubules that are required for cell division and proliferation. Most of the drugs that affect microtubule polymerization and dynamics, such as paclitaxel, are highly toxic. Therefore, a need exists for microtubule stabilizing agents that are less toxic than taxol for treating, preventing or inhibiting diseases and disorders associated with microtubule formation. (more...)

Cancer is the result of cumulative multiple genetic mutations, which result in the activation of oncogenes and/or the inactivation of tumor suppressor genes. It is the differential expression of these critical genes and their downstream effectors that enables cells to override growth controls and undergo carcinogenesis. While a variety of methods are currently employed to isolate genes associated with particular differential phenotypes, these techniques identify tissue-enriched mRNAs rather than tissue-specific proteins. Thus, there remains a need for a differential screening technique that provides actual confirmation of the presence of a protein product, not just the capacity to synthesize a protein. In addition, there is a need for proteins with antigenic determinants that may be recognized by the immune system. (more...)

Stroke and CNS injuries together cost Americans an estimated $75 billion a year in medical and rehabilitation expenses and lost productivity. Currently, there are no effective, clinically approved methods that promote nerve regeneration and subsequent restoration of CNS function. New research from the University of California has identified a potential therapeutic target for modulating neuron outgrowth. An antigen, present on most cells but long thought to be absent from neuronal cells, has been detected on nerve cells during embryonic brain development. This observation raised the question as to what role this antigen might play in neuronal guidance and axon growth. (more...)

Fusobatcerium nucleatum is an anaerobic Gram-negative microorganism that is commonly found in the mouth. For example, Fusobacterium nucleatum is the most frequently isolated pathogen from periodontal disease sites and is believed to be an initiator of periodontal diseases. Moreover, this bacterium is commonly found in abscesses and other infections in the abdomen, blood, chest, lung, sinuses, and female genital tract. Several F. nucleatum proteins that are believed to be associated with F. nucleatum pathogenesis have been identified, but their evaluation has been hampered by a lack of systems for genetic manipulation of this microbe. Therefore, there is a need for reliable gene transfer and expression systems for F. nucleatum. (more...)

Narcolepsy is a neurological disorder characterized by a sudden onset of sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Since the causes of this disease were not known until recently, the treatments for narcolepsy have been purely symptomatic, such as the use of stimulants to prevent sleepiness and antidepressants to reduce cataplexy. However, such treatments are often ineffective, have negative side effects, and do not address the underlying causes of the disease. Researchers at the University of California have obtained the first evidence from both human and a model animal system showing that narcolepsy involves a highly localized neurodegenerative process. Based on these findings, the UC researchers were able to identify several drugs that can delay the onset of symptoms and markedly reduce their intensity by suppressing the process. Success with these animals suggests that these discoveries may provide several very promising novel modes of treatment for narcolepsy in humans that could alter the course and progression of the disorder, as well as offer specific molecular targets for further drug development. These inventions point the way to treatments based not on an imprecise management of particular symptoms, but rather on control of the underlying disease mechanism. (more...)

Gels based on high molecular weight polyethylene glycol (PEG) have been used for many biological applications because of their low immunogenicity. Conventional gels incorporate solid-phase components, constraining their manipulation and use in a variety of areas such as molecular drug delivery. Gels that can function without solid-phase components would help to overcome many of these difficulties. (more...)

Inflammation is a significant clinical issue, the prevention and control of which is of prime importance. There are two main types of inflammation, called cellular inflammation and neurogenic inflammation. Cellular inflammation is mediated by activation of specific immune cells, whereas neurogenic inflammation is mediated directly by activation of nociceptive and thermal-sensitive endings in tissues. Much research has been devoted to the development of compounds having anti-inflammatory properties, particularly from marine animals. For example, topsentins, nortopsentins, dragmacidin, homocarbonyltopsentins, and hamacathins are a group of compounds, called bis-heterocyclic compounds, derived from sea sponges that have been shown to have inhibitory activity against cellular inflammatory responses. (more...)

Aminobutyric acid (GABA) is the major inhibitory amino acid in the mammalian brain, and the GABArho receptors are highly expressed in mammalian visual pathways. Drugs that interact selectively with the GABArho subtype are, therefore, likely to have distinct enhancing or depressing effects upon visual processing without untoward actions upon other aspects of brain function. Also, because of its unique properties, drugs that act on GABArho receptors may have important uses in clinical and experimental medicine related to diseases of the brain. University of California researchers have successfully synthesized a compound that acts as a selective antagonist of GABArho receptors. This compound, and its derivatives, may have important uses for basic neurobiological studies and may also be a useful drug in clinical and experimental medicine. (more...)

: Drugs to treat inflammation and pain in humans and animals are in constant demand. Though some such drugs already exist, there are many conditions for which a more potent treatment is desirable. (more...)

A research scientist at the University of California has discovered a drug that is effective in inducing long term potentiation of synaptic transmission. (more...)

A large patent portfolio around pseudopterosin compounds and their use as anti-inflammatories, analgesic agents, wound healing agents and burn treatments (more...)