Pain Control by the Selective Local Ablation of Nociceptive Neurons

The vanilloid receptor (VR) is a cation channel predominantly expressed on the peripheral processes and perikarya of nociceptive primary afferent neurons. Previous studies have shown that activation of the peripheral receptors by agonists such as capsaicin from hot peppers, or the much more potent resiniferatoxin, produces acute pain sensation which may be followed by desensitization. These inventors discovered that administration of VR agonists in the vicinity of neuronal cell bodies expressing the VR receptor can actually destroy those cells.

Small Molecule Inhibitors of Clk and Dyrk Kinases for Potential Therapeutic Intervention of Down Syndrome, Alzheimer's Disease and Cancer

This technology includes small molecule inhibitors of the cdc2-like kinase (Clk) and Dyrk kinase which can restore splicing outcomes within many dysregulated splicing events potentially reversing phenotypes associated with diseases associated with abnormal splicing. The Clks regulate the alternative splicing of microtubule-associated protein tau and are implicated in frontotemporal dementia and Parkinson's disease through the phosphorylation of splicing factors (SF).

Identification and Use of 12/15-Lipoxygenase (LOX) Inhibitors for Post-Strike Treatment

This technology includes the identification and use of 12/15-lipoxygenase (LOX) inhibitors, including ML351 and related analogs, for post-stroke treatment. The 12/15-LOX directly oxidizes lipid membranes leading to their direct attack. After a stroke, the activity of 12/15-LOX is upregulated and is thought to contribute to increased neuronal loss and blood-brain barrier leakage. A high-throughput screen was undertaken to find inhibitors, which were then subjected to medical chemistry optimization.

Compounds and Methods for Treating Brain Injury

This technology includes MRS4322, which is an A3 agonist that is currently being evaluated for treatment of traumatic brain injury. Although its affinity in the receptor is in the micromolar range, it enters the brain in sufficient concentration to activate a protective CNS receptor, A3 adenosine receptor. Potential applications of such A3 agonists could also include neurodegenerative conditions.

A Novel Adeno-Associated Virus for Gene Therapy

Scientists at the NIH disclosed a novel adeno-associated virus (AAV) termed "44-9." AAV44-9 based vectors have high gene transfer activity in a number of cell types, including salivary gland cells, liver cells, and different types of neurons (e.g., cells of the cortex, olfactory bulb, and brain stem, and Purkinje cells of the cerebellum). These vectors can increase the transduction efficiency and decrease the potential of being neutralized by preexisting antibodies compared to the wild type AAV.

Vitamin C renal leak as a clinical diagnostic tool in the detection, monitoring, and management of acute and chronic diseases

This technology includes a clinical diagnostic tool for measuring vitamin C elimination by human kidneys that can be used for detecting, monitoring, and managing acute and chronic diseases. Findings revealed significant associations between vitamin C renal leak status and clinical variables affecting renal function and blood glucose. The technology uses vitamin C depletion-repletion kinetics and pharmacokinetic models to establish a physiological vitamin C renal threshold.

Engineering Neural Stem Cells Using Homologous Recombination

Methods for modifying the genome of a Neural Stem Cell (NSC) are disclosed. Also, methods for differentiating NSCs into neurons and glia are described. NSCs are multipotent, self-renewing cells found in the central nervous system, capable of differentiating into neurons and glia. NSCs can be generated efficiently from pluripotent stem cells (PSCs) and have the capacity to differentiate into any neuronal or glial cell type of the central nervous system.

Methods of Treating or Preventing Pruritis (Itch)

This technology provides a novel method of treating or preventing pruritis (itch) using natriuretic polypeptide b (Nppb) blocking agents. Itch (also known as pruritis) is a sensation that may be perceived as an unpleasant skin irritation and may drive an urge to scratch. Conditions such as, for example, psoriasis, atopic dermatitis, renal failure, liver cirrhosis and some cancers may cause persistent itch. Itch is triggered by somatosensory neurons expressing the ion channel TRPV1 (transient receptor potential cation channel subfamily V member 1).

mNFHcre Transgenic Mice

Knockout mouse is a valuable model to study biological functions of target genes. When Cre expressing mice are bred with mice containing a loxP-flanked gene, the gene between the loxP sites will be deleted in the offsprings. Scientists at the NIH have generated mNF-H-cre transgenic mouse lines that express Cre recombinase under the control of the promoter of the neurofilament-H gene, which is expressed in the late stage of neuronal maturation. The transgenic mice express cre in neurons (but not astrocytes) with highest expression in the cortex and hippocampus.

Deuterated alpha5 Subunit-selective Negative Allosteric Modulators of Gamma-Aminobutyric Acid Type A Receptors as Fast Acting Treatments for Depression and Mood Disorders

This technology includes GABAa a5 Negative Allosteric modulators (GABAa a5 NAMs) which have been recently discovered to act as fast-acting antidepressants in a variety of mouse models of depression. These NAMs are actively metabolized in vivo. This invention involves the conceptualization and synthesis of GABAa a5 NAM molecules with a deuterium in the active metabolic position. This significantly increased the metabolic stability, while still retaining the antidepressant activity.