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This technology is a collection of small molecules screened for their ability to prevent or reduce the cytotoxic effects of the protein, Huntingtin. Huntington's disease is a neurodegenerative disorder due to a dominantly acting expansion of a CAG trinucleotide repeat in exon 1 of the Huntington (HTT) gene resulting in production of the altered (mutant) protein Huntingtin, which has a long chain of polyglutamine (poly Q) attached to the exon 1 encoded protein sequence.

The present invention is directed to novel small molecule agonists of the mammalian relaxin family receptor 1 (RXFP1), including human RXFP1. Activation of RXFP1 induces: 1) vasodilation due to up-regulation of the endothelin system; 2) extracellular matrix remodeling; 3) moderation of inflammation by reducing levels of inflammatory cytokines; and 4) angiogenesis. Small molecule agonists of RXFP1 may be useful in treating acute heart failure (AHF), scleroderma, fibrosis, other conditions associated with the biology of relaxin, and in improving reproductive health and wound healing.

Cyclodextrins (CD), alone or in combination with other agents (e.g., vitamin E), as therapeutics for the treatment of lysosomal storage disorders (LSDs) caused by the accumulation of non-cholesterol lipids.

The invention pertains to derivatives of docosahexaenoylethanolamide (synaptamide or DEA) and their use in inducing neurogenesis, neurite growth, and/or synaptogenesis. As such, these DEA derivatives can be used as therapeutics for neurodegenerative diseases such as traumatic brain injury, spinal cord injury, peripheral nerve injury, stroke, multiple sclerosis, autism, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis. The DEA derivatives of the invention have increased potency and hydrolysis resistance as compared to native DEA.

Novel tocopherol derivatives and tocopheryl quinone derivatives useful in the decrease of lysosomal substrate accumulation, the restoration of normal lysosomal size, and the treatment of lysosomal storage disorders (LSDs) are provided. The inventors have discovered that tocopherol and tocopheryl quinone derivatives with side chain modifications (such as terminal tri-halogenated methyl groups) exhibit improved pharmacokinetics, modulation of mitochondrial potential and restoration of some LSDs phenotypes.

Cells, cell culture methods, and cell culture media compositions useful for producing and maintaining iPSC-derived cell lines that are of higher purity and maintain cell type integrity better than current iPSC-derived cell lines are disclosed. Human induced pluripotent stem cells (hiPSCs) can be generated by reprogramming somatic cells by the expression of four transcription factors. The hiPSCs exhibit similar properties to human embryonic stem cells, including the ability to self-renew and differentiate into all three embryonic germ layers: ectoderm, endoderm, or mesoderm.

There is evidence that the metabolic effects of endocannabinoids are mediated by CB1 receptors in peripheral tissues. While prior attempts at generating CB1 receptor blockers have had serious neuropsychiatric side effects, inventors at NIH have discovered compounds that block CB1 receptors with reduced brain penetrance. In addition, some of these compounds also have a direct inhibitory effect on inducible nitric oxide synthase (iNOS), whereas another group of the compounds directly activates AMP kinas.

Insulin-dependent diabetes mellitus (IDDM) affects close to one million people in the United States. It is an autoimmune disease in which the immune system produces antibodies that attack the body's own insulin-manufacturing cells in the pancreas. Patients require daily injections of insulin to regulate blood sugar levels. The invention identified two proteins, named IA-2 and IA-2beta, that are important markers for type I (juvenile, insulin-dependent) diabetes. IA-2/IA-2beta, when used in diagnostic tests, recognized autoantibodies in 70 percent of IDDM patients.

This invention is a platform technology that pertains to the advantages of conjugating therapeutics to Evans Blue thus providing long lasting pharmacokinetic profiles by complexing with albumin. Notably, albumin bound therapeutic- or prodrug-Evans Blue conjugates provide a complex with a total molecular size above 60 kDa thus eliminating the risk for renal clearance. Interestingly, since albumin also crosses the blood-brain barrier and since all circulating Evans Blue is bound to albumin, Evans Blue bound therapeutics or prodrugs can also cross the blood-brain barrier.

3D spheroids have emerged as powerful drug discovery tools given their high-throughput screening (HTS) compatibility. The present invention presents a method for generating functional neural spheroids with differentiated human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes at cell type compositions mimicking specific regions of the human brain.