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Novel Agonist alpha2aAR Analgesics

Brief description not available

(SD2021-057) Electro-optical mechanically flexible microprobes for minimally invasive interfacing with intrinsic neural circuits

Microelectrodes are the gold standard for measuring the activity of individual neurons at high temporal resolution in any nervous system region and central to defining the role of neural circuits in controlling behavior.Microelectrode technologies such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision. However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings. State of the art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity.Although these probes have advanced the field of recordings, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins. However, given the strong light scattering and high absorption properties of neural tissue optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart.Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures. These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. However, the need to reduce the device footprint to minimize immune responses for long-term recordings is still present.

Novel Estrogen Receptor ß (ERß) Drugs for the Treatment of Multiple Sclerosis (MS)

Prof. Seema K. Tiwari-Woodruff from the University of California, Riverside, Prof. John Katzellenbogen and colleagues from the University of Illinois have developed novel estrogen receptor β (ERβ) drugs for the treatment of MS. These novel MS drugs are specific for ERβ and have tremendous potential for the treatment of MS as well as other neurodegenerative diseases. In general, estrogens have anti-inflammatory and neuroprotective activities and clinically reduce the severity of MS and other neurodegenerative diseases. The compounds are more superior to other estrogenic drugs due to their specificity for ERβ and lack of undesirable effects such as feminization and increased risk of cancer. Fig 1: Therapeutic treatment with the UCR ERβ ligands began at peak disease (day 17) and was continued daily till day 36. ERβ ligands (blue, and orange) significantly attenuated clinical disease severity compared to vehicle treatment (red).  

Device for Spinal Dural Repair

Dural tear is a frequent and costly complication of spinal surgery, which can cause cerebrospinal fluid (CSF) leakage, triggering additional, serious post-operative difficulties. Researchers at UC Irvine have developed a new method and device to mitigate dural tears in a rapid, safe, and water-tight manner

Inhibitors of Bromodomain and Extra-Terminal (BET) Family Proteins as Potential Treatments for Drug-Resistant Tumors

Researchers at the University of California, Davis have developed small molecule inhibitors for use in treating drug-resistant tumors – including cancerous tumors.

Intranasal Delivery of Oligonucleotides for Neurodegenerative Diseases

Delivery of oligonucleotide therapy to the central nervous system remains challenging. Neurodegenerative diseases, such as Huntington’s disease and Spinal Muscular Atrophy, can require intrusive and regular treatments, therefore a non-invasive delivery system would be very beneficial to patients. UC Irvine researchers have proposed a new method of therapeutic delivery utilizing a SARS-CoV-2 pseudovirus. Delivered intranasally, this system has the ability to bypass the blood brain barrier, making it an exciting approach to decrease risk for patients and ease the treatment process.

Novel Positron Emission Tomography Agents for Imaging Neurodegeneration

New positron emission tomography (PET) imaging agent developed that uniquely binds to synucleinopathies and tauopathies in the Parkinson’s brain and may therefore serve as an early diagnostic marker.

Agents for Mitochondrial Biogenesis

Researchers at the University of California, Davis, have developed compounds for the potential prevention and treatment of mitochondrial dysfunction disorders.

Co-Administration Therapy to Prevent Neurodegeneration and Enhance Neuroprotection

Neurodegenerative diseases are a broad category of illnesses expected to affect 1 in 4 Americans. As they have a variety of underlying mechanisms and pathologies, there are currently no effective methods to prevent or modify disease progression. UCI researchers have developed a potential treatment utilizing a novel combination of two compounds for the abatement of brain inflammation and degeneration.

Virtual Reality For Anhedonia Program

UCLA researchers in the Department of Psychology have developed a behavioral training program for the improvement of anhedonia.

Exosome-Mimicking Nanovesicles

Researchers at the University of California, Davis have developed a method of synthesizing stem cell-derived, exosome-mimicking, nanovesicles that have the therapeutic potential to rescue apoptotic neurons in culture.

Steroid Regulation Of Inwardly Rectifying K+ Channel As Therapeutics Tool

UC Berkeley researches have discovered a new physiological modality of a potassium channel that is linked to the process of fluid regulation in the brain and is expressed in the choroid plexus (CP) and retinal pigment epithelia. CP is the main producer of cerebrospinal fluid that serves as a buffer to protect the brain, provides it with nutrients and removes waste products. The researchers have shown that application of progesterone resulted in strong potentiation of the inwardly rectifying potassium channel. The potentiation was progesterone-specific and independent of other known membrane progesterone receptors expressed in CP. 

Novel Treatment For Alzheimer’s Disease and Dementia

Pathological accumulation of phosphorylated Tau (pTau) and accumulation of amyloid-beta (Ab) fragments are the two major biochemical hallmarks of Alzheimer’s disease (AD). Effective strategies to remove Ab in AD-patient brains have been developed, but have not yet shown efficacy to slow cognitive decline in clinical trials. This finding has led to the idea that targeting Tau or combinatorial strategies that target both Tau and Ab are required to treat AD. Genetic, epidemiologic, and biochemical evidence suggests that predisposition to AD may arise from altered cholesterol metabolism, although the molecular pathways that may link cholesterol to AD phenotypes are only partially understood. Stimulation of a brain specific cytochrome that converts cholesterol to 24-hydroxycholesterol, which in turn reduces cholesteryl ester. Reduction of cholesteryl ester has been demonstrated to reduce pathological Tau phosphorylation in human neurons made from induced pluripotent stem cells. Also, low dose Efavirenz/Sustiva reduces neurofibrillary tangles in a mouse model. The pathway may run from cholesteryl ester to Tau via the proteasome.

Metal‐Binding Pharmacophore Library Yields the Discovery of a Glyoxalase 1 Inhibitor for Potential Treatment of Depression and Related Psychiatric Illnesses.

Anxiety and depression are the two most common psychiatric disorders in the U.S. and affect approximately one-in-five adults at some point in their lifetime. Depression is the leading cause of worldwide disability; anxiety disorders are highly comorbid with depression. Presently, there are several drugs approved by the U.S. Food and Drug Administration for the treatment of both anxiety and depression; however, these drugs have several important limitations. Antidepressant drugs are not effective in all patients, take weeks to produce therapeutic effects, and produce side effects that limit their use. Anxiolytic drugs produce sedating side effects and have significant abuse liability. Therefore, there is an urgent need for better therapeutic agents. Recent studies using both genetic and pharmacological techniques have implicated GLO1 in numerous behaviors, including several that are relevant to depression and anxiety.

Oldest-Old Mri Registration Template

MRI scans of patients/participants can be compared to template scans in order to identify differences or changes in brain anatomy. However, the templates that are used are typically of young brains, which lack the atrophy that naturally occurs in the aged brain. UCI researchers have developed a template for oldest old images (90+ age group) that takes into consideration the natural anatomical changes that can occur with aging.

Effective Repetitive Transcranial Magnetic Stimulation (rTMS) Taking in Account Real-Time Frequency and Phase Of Intrinsic Brain Activity

Current research and practice in the field of therapeutic rTMS is not taking into account 1) inter-individual variability 2) variability between brain areas 3) variability or differences between oscillations in distinct and overlapping frequency bands, 4) existence of high- and low-excitability phase periods in each oscillatory cycle. Clinical treatments with rTMS and experimental research findings show mixed effects, with rTMS protocols inducing variable degrees of brain plasticity over subjects and sessions.

Peptide Mediated Oligonucleotide Delivery to the CNS

Many diseases of the central nervous system (CNS) arise from the accumulation of proteins such as α-synuclein (aSyn) in Parkinson’s Disease (PD) or Aß in Alzheimer’s disease (AD). The ability to regulate the expression at the gene transcription level would be beneficial for reducing the accumulation of these proteins or regulating expression levels of other genes in the CNS. aSyn also accumulates in other neurodegenerative diseases including dementia with Lewy Body (DLB), multiple system atrophy (MSA) and Gaucher’s disease. This means that regulation of aSyn expression may be crucial to the therapeutic control of numerous neurodegenerative diseases.

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.

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.

Brain-Specific Kinase Inhibition to Mitigate Systemic Toxicity

The goal of this invention is to overcome the challenges of previous approaches by selectively targeting treatments to the CNS without peripheral toxicity. Kinase inhibition is targeted to the central nervous system (CNS) by combining brain-permeable kinase inhibitors and a brain-impermeable blocking molecule.

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).

(SD2019-232) 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.  

Novel Small Molecules to Prevent Neurodegenerative Diseases

UCSF scientists have developed a novel biophysical-biochemical screening platform to identify small molecules that prevent the oligomerization of alpha-synuclein: the rate-limiting step in the formation of toxic fibrils in the pathologies of Parkinson’s disease, Lewy Body Dementia, and other neurodegenerative diseases. With this technology, novel families of small molecules have been found with the capacity to reverse multiple pathogenic markers of disease progression in cells.

Strategy for in vivo Depalmitoylation of Proteins and Therapeutic Applications Thereof

The neuronal ceroid lipofuscinoses (NCLs), commonly grouped together as Batten disease, are the most common neurodegenerative lysosomal storage diseases of the pediatric population. No cure for NCL has yet been realized. Current treatment regimens offer only symptomatic relief and do not target the underlying cause of the disease. Although the underlying pathophysiology that drives disease progression is unknown, several small molecules have been identified with diverse mechanisms of action that provide promise for the treatment of this devastating disease. On this point, several researchers have reported the use of potential drugs for NCL patient lymphoblasts and fibroblasts, along with neurons derived from animal models of NCL disease. Unfortunately, most of these studies were inconclusive or clinical trials or follow-up results were not available. High concentrations employed and toxicity of the small molecules are clear disadvantages to the use of some of the corresponding derivatives as potential drugs. To circumvent these effects, development of nontoxic alkyl cysteines would be useful for the non-enzymatic and chemo-selective depalmitoylation of S-palmitoyl proteins, which hold good promise as an effective treatment for neuronal ceroid lipofuscinoses.

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.

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