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Newborn Biomarkers of Cumulative Autism Risk Factors

Researchers at the University of California, Davis have identified DNA methylation biomarkers in placenta, as well as maternal and newborn blood, allowing early autism diagnosis and risk assessment.

Genetic Polymorphisms Linked to Age-Related Eye Disorders and Drug Response

Researchers at UC Irvine have identified genetic polymorphisms associated with disease progression and responsiveness to treatment with Tetracosapentaenoic acid (24:5 n-3) for age-related eye disorders such as age-related macular degeneration (AMD), diabetic retinopathy and glaucoma. These variations found in the ELOVL2 gene are associated with AMD progression and the varying responses individuals have to AMD treatments, including preventative measures. Additionally, these genetic variations have applications in human identification.

Unsupervised Positron Emission Tomography (PET) Image Denoising using Double Over-Parameterization

Researchers at the University of California, Davis, have developed a novel imaging system that improves the diagnostic accuracy of PET imaging. The system combines machine learning and computed tomography (CT) imaging to reduce noise and enhance resolution. This novel technique can integrate with commercial PET imaging systems, improving diagnostic accuracy and facilitating superior treatment of various diseases.

Systems and Methods of Single-Cell Segmentation and Spatial Multiomics Analyses

Researchers at the University of California, Davis have developed a novel cell segmentation technology for accurate analysis of non-spherical cells and that offers a comprehensive, high-throughput approach for analyzing the transcriptomic and metabolomic data to study complex biological processes at the single-cell level.

Silent Speech Interface Using Manifold Decoding Of Biosignals

Researchers at the University of California, Davis have developed a technology that provides a novel method for decoding biosignals into speech, enhancing communication for individuals with speech impairments.

Stabilized Amyloid Oligomers and Applications for Alzheimer’s Research and Treatment

An innovative approach to advancing Alzheimer's disease research, detection, and treatment through the development of synthetic amyloid peptides and oligomers.

(SD2022-222) Optimized CAG repeat‐targeting CRISPR/cas13d designs

Reseachers from UC San Diego demonstrated a proof of principle for a CAGEX RNA-targeting CRISPR–Cas13d system as a potential allele-sensitive therapeutic approach for HD, a strategy with broad implications for the treatment of other neurodegenerative disorders.

Use of Ophthalmic Acid for treatment of Parkinson’s disease

Researchers at UC Irvine have identified Opthalmic acid (Ophthalmate, OA) for treatment of Parkinson’s disease (PD), a degenerative neurological disorder that affects 1-2% of people over the age of 60. PD is characterized by progressive motor symptoms such as tremor, rigidity, slowness of movement and difficulty with balance. There is currently no cure for Parkinson’s disease, only treatments to help manage the symptoms. Pharmacological strategies for treating PD depend mainly on replacing lost dopamine due to the degeneration of dopamine neurons in the substantia nigra compacta. Six decades after its initial use, L-3, 4-dihydroxyphenylalalnine (L-DOPA), the dopamine precursor, remains the standard of care for treatment of PD motor symptoms. L-DOPA can readily cross the blood-brain barrier (BBB) and is converted to dopamine by aromatic amino acid decarboxylase (AADC). Initial treatments with L-DOPA can provide great relief from motor symptoms, but over time its therapeutic effects diminish, and dyskinesia (abnormal involuntary movements) can increase in PD patients. Ophthalmic acid acts as a novel neurotransmitter to counteract the motor symptoms in animal models of PD, with a longer duration of action. Ophthalmic acid can be used as a novel drug for treatment of PD and other neurological disorders.

Operant Behavioral Assay

Researchers at the University of California, Davis have developed an operant behavioral assay to study thermosensation, pain, or avoidance and tolerance of an animal to noxious environments.

(SD2022-119) MICROELECTRODE GRID WITH A CIRCULAR FLAP FOR CONTINUOUS INTRAOPERATIVE NEUROMONITORING

Researchers from UC San Diego and Oregon Health Science Univeristy developed a microelectrode grid for continuous interoperative neuromonitoring. The microelectrode grid includes a flexible substrate with low impedance electrochemical interface materials on conducting metal pads. The metal pads are connectable to stimulation/acquisition electronics through metal lead interconnects forming stimulation and recording channels and eventually to bonding pads. A flap within the substrate is movable away from the remainder of the substrate while at least some of the metal pads on the remainder of the substrate can remain in contact with an organ when the flap is moved away from the remainder of the substrate.

Allele Selective Epiediting Of Huntington's Disease Locus

Huntington's disease is an autosomal dominant neurodegenerative disease that has a wide impact on a person's functional abilities and usually results in movement, cognitive, and psychiatric disorders. A treatment for HD that can selectively reduce expression of a mutant copy of the HTT gene (e.g., while having little to no effect on expression of a normal copy of the HTT gene) is highly desirable.UC Berkeley researchers have discovered methods and compositions that take advantage of naturally occurring single nucleotide polymorphisms (SNPs) in the regulatory region of the HTT gene to distinguish between an HTT gene allele containing a pathogenic CAG trinucleotide repeat expansion and an HTT allele that lacks a pathogenic CAG trinucleotide repeat. Potential benefits of using this strategy include 1) lowering both mutant mRNA and mutant protein levels while normal allele remains unaffected, 2) lowering levels of toxic HTTexon11 species and 3) by lowering transcription across the mutant CAG repeats could slow down repeat expansion in mutant allele poten5ally leading to a delay in age of onset. 

Affinity Peptides for Diagnosis and Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 and Zika Virus Infections

Researchers at the University of California, Davis have developed a technology to expedite COVID-19 diagnosis and treatment using viral spike protein (S-protein) targeted peptides Zika virus envelop protein.

Design Of Functional Protein Materials Based on Beta-Rippled Sheet Architectures

The rippled sheet was proposed by Pauling and Corey as a structural class in 1953. Following approximately a half century of only minimal activity in the field, the experimental foundation began to emerge, with some of the key papers published over the course of the last decade. Researchers at UC Santa Cruz have explored the structure of and have discovered ways to form new beta rippled sheets. 

(SD2024-124) Predicting neural activity at depth from surface using multimodal experiments and machine learning models

Researchers from UC San Diego's Neuroelectronic Lab (https://neuroelectronics.ucsd.edu/) demonstrate that they can predict neural activity at deeper layers of the brain by only recording potentials from brain surface. This was achieved by performing multimodal experiments with an ultra-high density transparent graphene electrode technology and developing neural network methods to learn nonlinear dynamic between different modalities. They used cross modality inference to predict the activity at deep layers from surface. Prediction of neural activity at depth have the potential to open up new possibilities for developing minimally invasive neural prosthetics or targeted treatments for various neurological disorders.

(SD2022-177 ) Flexible, insertable and transparent microelectrode array to detect interactions between different brain regions

Researchers from UC San Diego's Neuroelectronics Lab invented an implantable brain electrode technology which allows recording interactions between different cortex regions or interactions of cortex with other subcortical structures. The technology is called Neuro‐FITM. Flexibility and transparency of Neuro‐ FITM allow integration of electrophysiological recordings with any optical imaging (such as high resolution multiphoton imaging) or stimulation technology (such as optogenetics).

(SD2022-066) Simultaneous assessment of afferent and efferent visual pathways using multi‐focal steady‐state visual evoked potenital method to facilitate the diagnosis and prognosis of individuals with neurological diseases.

Researchers from UC San Diego have developed a patent-pending wearable device for concurrently assessing afferent and efferent visual functions. The invention details novel mobile brain-computer interfacing methods and systems for concurrently assessing afferent and efferent visual functions.

COMPOUNDS FOR MODULATING EPITHELIAL 15-(S)-LIPOXYGENASE-2 AND METHODS OF USE FOR SAME

Lipoxygenases (LOX) are enzymes that catalyze the peroxidation of certain fatty acids. The cell membrane is mostly made of lipids (which include fatty acids), and peroxidation can cause damage to the cell membrane. The human genome contains six functional LOX genes that encode for six LOX enzyme variants, or isozymes. The role that each LOX isozyme plays in health and disease varies greatly, spanning issues such as asthma, diabetes, and stroke. LOX enzymes are extremely difficult to target due to high hydrophobicity. Potential leads are often ineffective because they are either not readily soluble or not selective for a particular LOX enzyme.  Studies have implicated human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) in various diseases. h15-LOX-2 is highly expressed in atherosclerotic plaques and is linked to the progression of macrophages to foam cells, which are present in atherosclerotic plaques. h15-LOX-2 mRNA levels are also highly elevated in human macrophages isolated from carotid atherosclerotic lesions in symptomatic patients. Children with cystic fibrosis had reduced levels of h15-LOX-2, which affects the lipoxin A4 to leukotriene B4 ratio. Furthermore, the interactions of h15-LOX-2 and PEBP1 changes the substrate specificity of h15-LOX-2 from free polyunsaturated fatty acids (PUFA) to PUFA-phosphatidylethanolamines (PE), leading to the generation of hydroperoxyeicosatetraenoic acid (HpETE) esterified into PE (HpETE-PE). Accumulation of these hydroperoxyl membrane phospholipids has been shown to cause ferroptotic cell death, which implicates h15-LOX-2 in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.  

In Vivo Gene Editing Of Tau Locus Via Liponanoparticle Delivery

Delivery technologies such as lipid nanoparticles (LNP) offer significant advantages over the delivery of free RNA for various RNA therapeutic, vaccine, and basic science applications. UC Berkeley researchers developed a new class of lipid nanoparticle (LNP) which is effective in delivering various types of nuclei acids in different tissues.  The LNP was successfully tested in in-vivo mouse models and therefore poses a significant promise in the gene editing field. The lipid formulation was packaged together with CRISPR Cas9 and a gRNA targeting the endogenous Tau locus. Tau dysrregulation is a pathological feature of Alzheimers disease, thus the invention provides a means to intervene in the development of pathological states associated with Tau aggregate formation. 

15LOX1 Inhibitor Formulation Determination For IV Administration

Lipoxygenases catalyze the peroxidation of fatty acids which contain bisallylic hydrogens between two cis double bonds, such as in linoleic acid (LA) and arachidonic acid (AA). Lipoxygenases are named according to their product specificity with AA as the substrate because AA is the precursor of many active lipid metabolites that are involved in a number of significant disease states. The human genome contains six functional human lipoxygenases (LOX) genes (ALOX5, ALOX12, ALOX12B, ALOX15, ALOX15B, eLOX3) encoding for six different human LOX isoforms (h5-LOX, h12S-LOX, h12R-LOX, h15-LOX-1, h15-LOX-2, eLOX3, respectively). The biological role in health and disease for each LOX isozyme varies dramatically, ranging from asthma to diabetes or stroke. The nomenclature of the LOX isozymes is loosely based on the carbon position (e.g., 5, 12, or 15) at which they oxidize arachidonic acid to form the corresponding hydroperoxyeicosatetraenoic acid (HpETE), which is reduced to the hydroxyeicosatetraenoic acid (HETE) by intracellular glutathione peroxidases. Lipoxygenase inhibitors are difficult to formulate due to challenges with solubility and other factors, therefore new formulations are needed.

ML351 As Treatment For Stroke And Ischemic Brain Injury

Lipoxygenases form a large family of enzymes capable of oxidizing arachidonic acid and related polyunsaturated fatty acids. One such lipoxygenase, 12/15 LOX can oxidize both the C-12 and C-15 of arachidonic acid, forming 12- or 15-hydroperosyarachidonic acid (12- or 15-HPETE). Lipoxygenases and their metabolites have been implicated in many diseases. In particular 12/15-LOX (also known as 15-LOX-1, 15-LOX, or 15-LO-1 in humans and L-12-LoX, leukocyte-type 12-LO, or L-12-LO in mice) plays a role in atherogenesis, diabetes, Alzheimer's, newborn periventricular leukomalacia, breast cancer, and stroke. Whatever the name, the protein is encoded by the gene ALOX15 in both mice and humans. Lox inhibitors are difficult to develop due to the mouse and human homologs having different substrate and inhibitor specificities - 12/15 LOX produces predominantly 15-HETE in humans and 12-HETE in mice. So existing inhibitors are not selective for 12/15 LOX with regard to other LOX isoforms. In addition, many are strong antioxidants and therefore may result in off-target effects. 

Three-dimensional organoid culture system for basic, translational, and drug discovery research

Researchers at UC Irvine have developed an organoid culture system capable of generating three-dimensional molecular gradients. This recapitulates in vivo tissue development more accurately than current two-dimensional organoid culture systems and will allow scientists to study human-specific disease mechanisms in native tissue.

A neuronal circuit analysis platform for drug discovery

Researchers at UC Irvine have characterized an electrophysiological-based drug discovery approach that offers a new modality with which to screen potential therapeutics and characterize mutations. This new level of analysis utilizes elements that are shared between rodents and humans, improving upon the uncertainties associated with rodent behavior. It also incorporates the full complexity of operations in a single assay, while rapidly specifying site(s) of action, thereby accelerating R&D for psychiatric illnesses.

Biological and Hybrid Neural Networks Communication

During initial stages of development, the human brain self assembles from a vast network of billions of neurons into a system capable of sophisticated cognitive behaviors. The human brain maintains these capabilities over a lifetime of homeostasis, and neuroscience helps us explore the brain’s capabilities. The pace of progress in neuroscience depends on experimental toolkits available to researchers. New tools are required to explore new forms of experiments and to achieve better statistical certainty.Significant challenges remain in modern neuroscience in terms of unifying processes at the macroscopic and microscopic scale. Recently, brain organoids, three-dimensional neural tissue structures generated from human stem cells, are being used to model neural development and connectivity. Organoids are more realistic than two-dimensional cultures, recapitulating the brain, which is inherently three-dimensional. While progress has been made studying large-scale brain patterns or behaviors, as well as understanding the brain at a cellular level, it’s still unclear how smaller neural interactions (e.g., on the order of 10,000 cells) create meaningful cognition. Furthermore, systems for interrogation, observation, and data acquisition for such in vitro cultures, in addition to streaming data online to link with these analysis infrastructures, remains a challenge.

Pharmacological fortification and/or restoration of protective nerve coverings via a novel therapeutic target

Researchers at UC Irvine have discovered a novel mechanism by which restoration of protective nerve coverings fails in degenerative disease like multiple sclerosis. While therapeutics to slow disease progression exist, there are currently none aimed at preventing or restoring damage to nerve coverings.

(2023-117) Resilience and Wisdom Training (RWT)

Stress and loneliness are biologically toxic factors with adverse effects on mental and physical health. The 2018 Gallup World Poll found a 25%–40% increase in stress, worry, and anger in the US from 2008 to 2018. Loneliness is associated with considerable distress, and older adults are vulnerable to loneliness due to losses, physical decline, and social isolation. The COVID-19 pandemic led to increased social isolation, though some older adults with higher levels of resilience and wisdom faced the pandemic with greater fortitude than younger adults.Aging is associated with numerous stressors that negatively impact older adults’ well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. 

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