Gaucher disease is a rare lysosomal storage disease that is characterized by a loss of function of the glucocerebrosidase (GCase) enzyme, which results in a decreased ability to degrade its lipid substrate, glucocerebroside. The intracellular build up of this lipid causes a broad range of clinical manifestations, ranging from enlarged spleen/liver and anemia to neurodegeneration. In Gaucher disease, the loss of GCase function has been attributed to low levels of the protein in the lysosomal compartment, resulting from improper GCase folding and transport.

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 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.

This invention is directed to adeno-associated virus (AAV) vector delivery of exendin-4 (Ex-4) to salivary glands as treatment for diabetes and obesity. Ex-4 is a potent and long-acting agonist of the receptor for glucagon-like peptide 1 (GLP-1). Scientists at NIDCR have shown that AAV-mediated delivery of Ex-4 resulted in improved glucose homeostasis and weight profile in two rat models of obesity and type 2 diabetes. Further, AAV-mediated delivery of Ex-4 to rat salivary glands resulted in localized and sustained expression of Ex-4 that was biologically active and well tolerated.

This technology provides novel antibodies and methods for diagnostics and treatment of disorders arising from dysregulation of the immune system using antibodies directed against glucocorticoid-induced tumor necrosis factor receptor family-related receptor ligand (GITRL). Also available are hybridomas producing anti-mouse GITRL monoclonal antibodies (clone 5F1).

The invention is directed to modification of a particular sugar by the enzyme arylsulfatase B (ARSB), which results in axon regeneration.

Sjögren's syndrome is an autoimmune disease that attacks salivary glands resulting in chronic dry mouth and dry eyes. Currently, there is no single diagnostic test to confirm the presence of Sjögren's. Physicians presently reach diagnosis after conducting a series of blood and functional tests for tear and salivary production. Diagnosis is further complicated as Sjögren's symptoms frequently mimic those of other autoimmune diseases (e.g., lupus, rheumatoid arthritis, etc.) and is often overlooked as dryness associated with medications being taken by the patient.

There is no vaccine for malaria, and there is growing resistance to existing anti-malarial drugs. Sexual stage-specific antigens are of interest as vaccine candidates because disruption of these antigens would reduce the fertility and, thus, the infectivity of the parasite.

Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice.

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.