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Use of Thiazolidinediones for Treatment of Eosinophilic Esophagitis Pathologic Remodeling

Esophageal inflammatory disorders are gaining increased recognition in both adults and children. One example is eosinophilic esophagitis (EoE), which is an emerging and fast-growing disorder characterized by high levels of eosinophils in the esophagus, as well as esophageal cellular changes such as basal zone hyperplasia and esophageal remodeling that includes fibrosis and smooth muscle dysfunction. These complications can lead to trouble swallowing, strictures,and food impactions. EoE is thought to be provoked, in at least a subset of patients, by food allergies or airborne allergen exposure. EoE diagnosis is often associated with other hypersensitivity disorders, including asthma, rhinitis, and other food and aeroallergen inhalant sensitivities. Diagnosis requires the finding of 15 or more eosinophils per high power field (eos/hpf) within esophageal mucosal biopsies. Although EoE is becoming more frequently diagnosed throughout developing countries, many aspects of the disease remain unclear including its etiology, natural history and optimal therapy. Symptoms of EoE often mimic those of gastroesophageal reflux disease (GERD) and include vomiting, dysphagia, pain and food impaction. In the absence of long-term treatment, up to 70-80% of adults with eosinophilic esophagitis (EoE) may go on to develop esophageal strictures. This disease now is likely to occur in 1 in 1000 people in the population and will have a dramatic effect on the patients’ quality of life. While there are therapies that control inflammation, not all patients respond to these therapies and continue to progress to fibrotic changes. There are currently no medical treatments to directly target esophageal fibrosis.

Biomimetic Conductive Hydrogels

UCLA researchers in the Department of Bioengineering have developed a novel electrically conductive scaffold system with a hyaluronic acid (HA)-based hydrogel for biomimetic research to treat spinal cord and other central nervous system (CNS) injuries.

Improvement To Retroviral Vectors Containing The Human Ubiquitin C Promoter

UCLA researchers in the Department of Molecular Biology have developed a lentiviral vector, “pCCLc-roUBC”, containing the cellular promoter from the human ubiquitin C gene (UBC), to improve transgene expression in retroviral vectors.

Heart Assist Device for Patients

Researchers at UCI have developed a cardiac assist device for patients with failing heart functions. The device contracts and expands the heart with the help of a pacemaker to help restore natural heart pace and blood flow.

Improved Highly Potent Specific Human Kunitz Inhibitor of Fibrinolytic Enzyme Plasmin

UCLA researchers in the School of Medicine have developed mutant polypeptides of the tissue factor pathway inhibitor-2 (TFPI-2) Kunitz domain 1 (KD1), which can serve as potent inhibitors of fibrinolysis.

New Indications For ENPP1 Inhibitors, Part Two

UCLA researchers in the Department of Medicine have developed small molecule ENPP1 inhibitors and monoclonal antibodies for treating myocardial infarction and ocular calcification.

New Indications For ENPP1 Inhibitors

UCLA researchers in the Department of Medicine have developed small molecule ENPP1 inhibitors and monoclonal antibodies for treating myocardial infarction and ocular calcification.

Combination Of Primary And Super-Charged NK Cells With Osteoclast Expanded CD8+ T Cells For Effective Immunotherapy Of Cancer

UCLA researchers in the Department of Dentistry have developed a novel combination immunotherapy using multiple immune cell types including NK and CD8+ T cells for the effective treatment of cancer.

Blocking Synaptogenesis For Chronic Pain Management

Gabapentin is used for treatment of seizures and hypersensitivity to pain. Researchers at UCI have employed low-dosage gabapentin immediately after injury to block the development of chronic pain.

Chemical Modulators of Nurr1

Long thought to be undruggable, Nurr1 is a nuclear receptor and transcription factor involved in the development, maintenance, and survival of midbrain dopaminergic neurons, which makes it an attractive target for developing therapeutics for such indications of Parkinson’s disease, multiple sclerosis, and schitzophrenia.

Antitumor Activity Of Sd-101 Alone Or In Combination With A-Pd-1 Therapy In Tumors Resistant To Anti-Pd-1

UCLA researchers in the Department of Medicine have developed a novel antitumor treatment that works alone or in combination with anit-PD-1 therapy to target interferon signaling-deficient tumors or tumors with alterations in the antigen presentation machinery, that are resistant to anti-PD-1 therapy.

Chimeric Kinase Inhibitors with Increased Activity

This invention describes newly generated kinase inhibitors that demonstrate enhanced and attenuated action over their parent kinase inhibitors. These molecules can be used alone but, when combined with novel blocking molecules, the action of these chimeric kinases can be targeted for action in the central nervous system (CNS).

Technologies that can be Used to Selectively Bind Messenger RNA and Enhance Protein Translation

Control of gene expression is a general approach to treat diseases where there is too much or too little of a gene product. However, while there are many methods which are available to downregulate the expression of messenger RNA transcripts, very few strategies can upregulate the endogenous gene product. The vast majority of gene regulatory drugs which are commercially available or being developed are designed to knockdown gene expression (i.e. siRNAs, miRNAs, anti-sense, etc.). There exist some methods to enhance gene expression, such as the delivery of messenger RNAs; although, therapeutic delivery of such large and charged RNA molecules is technically challenging, inefficient, and may not be practical. There are also classical gene therapy approaches where a gene product is delivered as viral-encoded products (AAV or lentivirus-packaged). However, these methods suffer from not being able to accurately reproduce the correct alternatively spliced isoforms in the right ratios in cells.  

Anti-Obesity Target

The global epidemic of type 2 diabetes is increasing at an alarming rate in both Westernized and developing countries. In the United States alone, it is estimated that there are at least 30 million people with this disease. Metabolic syndrome is 2 to 3 times more prevalent than type 2 diabetes and is usually the precursor state for this disease, indicating that this type 2 diabetes epidemic will not abate in the near future. Insulin resistance is a key etiologic feature of the metabolic syndrome and type 2 diabetes, and obesity is far and away the most common cause of insulin resistance in humans. There is a well-known parallel global epidemic of obesity, and the great majority of type 2 diabetic patients are obese. Therefore, it seems logical to conclude that the obesity epidemic is the underlying driver of the type 2 diabetes epidemic. Unfortunately, at the present time there are a limited number of therapeutics available as way of preventing or treating obesity.

NOVEL ANTIBODIES AGAINST EPHA2 FOR RESEARCH, DIAGNOSIS, AND TREATMENT OF CANCER

A novel monoclonal human antibody specific to the cell-surface exposed protein EphA2, which is over-expressed in many forms of cancer and is a validated therapeutic target.

New Treatment For Aortic Aneurysms

Aortic aneurysms account for 1-2% of deaths in Western countries, and despite improvements in surgical repair, morbidity and mortality remain high, especially with thoracic aortic aneurysms and dissections (TAAD). Degeneration of the medial layer of the aorta leads to aortic dilation and/or rupture; pathological changes in the media include progressive elastin fiber fragmentation, loss of smooth muscle cells, and proteoglycan accumulation. Mutations causing hereditary TAAD affect proteins regulating transforming growth factor-β signaling (e.g., Loeys-Dietz syndrome and Marfan syndrome), or components of the smooth muscle cell contractile apparatus. Aortic pathology has been attributed to smooth muscle cell phenotypic alterations and activation of stress pathways, leading to increased production of tissue-destructive matrix metalloproteinases and increased oxidative stress. Abdominal aortic aneurysms (AAAs) may share with TAAD some of these pathogenic mechanisms. While blood pressure control with β-adrenergic or angiotensin receptor blockers modestly improve the prognosis of patients with TAAD, there is no treatment to prevent the pathologic changes in the aorta.          

Development of a Method to Treat Alzheimer’s Disease by Protection of Synapses

NMDA receptors (NMDARs) are principal regulators of synaptic signaling in the brain. Modulation of NMDARs’ function and trafficking is important for the regulation of synaptic transmission and several forms of synaptic plasticity. Postsynaptic density protein 95 (PSD-95) acts as a scaffolding protein and stabilizes the surface and synaptic expression of NMDARs. NMDA receptors (NMDARs) are ionotropic glutamate receptors that are expressed throughout the nervous system and play crucial roles in neuronal development, synaptic plasticity, learning and memory. PSD-95 (Post Synaptic Density protein) or SAP90, a membrane-associated guanylate kinase (MAGUK), is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. It is almost exclusively located in the post synaptic density of neurons and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA receptors, and potassium channels. Postsynaptic loss does not precede obvious Aβ (beta-amyloid or amyloid beta) and Tau deposition, but instead appears to occur as Aβ and Tau pathologies advance. This indicates that PSD-95 is an excellent intrinsic biomarker for post synaptic mechanisms and its expression is reduced in brain tissue from patients with Alzheimer’s Disease (AD) as well as in mouse models of AD.

Using Bacteria for Gut Health Improvement and Weight Management

Researchers at the University of California, Davis have developed a method of using bacteriocin peptides to reduce gut inflammation, improve gut barrier function, and reduce obesity in humans.

Use Of Non-Ionic Copolypeptide Hydrogels For Cell Suspension And Cell And Molecule Delivery

UCLA researchers in the Departments of Bioengineering, Chemistry and Biochemistry, and Neurobiology have developed novel copolypeptide hydrogel formulations for the delivery of cells and molecules to locations throughout the body, including the central nervous system.

Antibody and Vaccine Therapy for C. diff. Infection

Clostridium difficile (C. diff.) infection is estimated to cause nearly 0.5 million illnesses in the US. C. diff. can cause severe gastrointestinal effects, including life-threatening inflammation, is contagious, and is an urgent antibiotic-resistant threat, according to the Centers for Disease Control and Prevention. UCI researchers have determined the crystal structure for the virulent C. diff. toxin, TcdB, and characterized sites to target for neutralization along with immunogens that can be used in vaccine strategies to prevent and treat C. diff. infection.

Nell-1 As An Anti-Osteoinflammatory, Disease-Modifying Anti-Arthritis Agent

UCLA researchers in the Department of Plastic Surgery and the School of Dentistry have developed a novel anti-osteoinflammatory agent for the prevention and suppression of arthritis disease progression.

Identification of a New Molecular Target and Methods for Treating Pancreatic Cancer

Pancreatic cancer is an aggressive disease with limited treatment options and a high mortality rate. Pancreatic cancer is the 3rd leading cause of cancer death in the United States; despite some recent advances in systemic therapy, survival remains dismal in large part due to its profound drug resistance and its propensity for early metastasis. Typically, diagnosis of pancreatic cancer occurs only with advanced stages of the disease since there are currently no early markers for detection. Individuals with pancreatic cancer have a poor prognosis due to the late diagnosis, the extent of metastasis, and ineffective treatments. Survival rates are dismal, with a one-year survival rate of 25% and a 5-year survival rate of 6%. Currently, approximately 20% of pancreatic cancer patients are able to undergo the Whipple procedure; this surgical procedure involves removal of the affected portion of the pancreas, leading to an increased survival rate. However, the remaining 80% of pancreatic cancer patients cannot undergo this treatment because their tumors or the extent of metastasis are too severe. In addition, pancreatic cancer is not typically responsive to radiation and chemotherapy. An alternative approach for the treatment of pancreatic cancer is a complete pancreatectomy followed by continual supplementation with digestive enzymes and insulin. Thus, more effective drugs are needed to increase the survival rate of pancreatic cancer patients. Targeting RORγ may lead to the design of a new class of therapeutics that can be used to treat this devastating disease.

A Method to Prevent the Myelin Abnormalities Associated with Arginase Deficiency

UCLA researchers in the Department of Surgery have developed a gene therapy to prevent dysmyelination (and other CNS abnormalities) as a result of arginase deficiency.

Exercise In A Pill: Compounds That Reproduce The Effects Of Exercise On Muscle Metabolism And Growth

UCLA researchers in the Department of Neurology have identified and synthesized small molecule analogs that activate skeletal muscle growth, mediated by calcium calmodulin kinase II signaling.

Treatment for Restoring Ureagenesis in Carbamoyl Phosphate Synthetase 1 Deficiency

UCLA researchers in the Department of Surgery have developed a gene therapy to treat carbamoyl phosphate synthetase 1 deficiency.

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