Glucocerebrosidase Activators as a Treatment for Gaucher Disease

This technology is a collection of small molecule activators of a genetically defective version of the enzyme called glucocerebrosidase (GCase), which causes Gaucher disease. Gaucher disease is a rare disease affecting 1 in 40,000 babies born. Ashkenazi Jews of eastern European descent (about 1 in 800 live births) are at particular risk of carrying this genetic defect. It is caused by inherited genetic mutations in the gene that encodes GCase, which result in reduced activity of the enzyme.

CD206 Small Molecule Modulators, Their Use and Methods for Preparation

Pancreatic ductal adenocarcinoma (PDA) accounts for more than 90% of pancreatic cancer cases, and it is one of the most aggressive malignancies with a 5-year survival rate of 6%. The high mortality rate caused by PDA is primarily from the lack of early diagnosis – it is often asymptomatic in early stages – and a poor response to conventional chemotherapy and radiotherapy. One of the major immune cell types present in the PDA microenvironment is a subset of macrophages commonly termed tumor-associated macrophages (TAM).

Autophagy Modulators For Use in Treating Cancer

Cancer cells can upregulate autophagy – cell destruction – as a response to chemotherapy. Investigators in Dr. Melvin DePamphilis’ laboratory at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have shown that compounds identified by screening a library of compounds blocks autophagy in some cancer cells (e.g., melanoma) but are not toxic to normal cells. Cancer cells with mutations in the BRAF oncogene are especially dependent on autophagy. Treatment of cancer cells with the BRAF mutation can increase the efficacy of chemotherapy.

Topical Sodium Nitrate Ointment for Sickle Cell Disease

Chronic leg ulcers are a debilitating vasculopathic complication for some patients with sickle cell disease (SCD). Prevalence of leg ulcers varies based on age and geographic location; about 5-10% of all SCD patients may suffer leg ulcers. These leg ulcers are painful, result in infections, hospitalization, disability, and negatively impact the patient’s social and psychological wellbeing on an ongoing basis.

Methods of Treating Giardiasis Using FDA-Approved Compounds

This technology includes a group of at least twenty-nine, diverse, commercially available compounds that are newly identified for activity against Giardia lamblia parasites. At least six of the candidate compounds, Bortezomib, Decitabine, Hydroxocobalamin, Amlexanox, Idarubicin, and Auranofin have preexisting FDA approval for human use for other (non-Giardia) conditions. Another three compounds, Fumagillin, Nitarsone and Carbadox have preexisting approval for veterinary use for non-Giardia conditions.

Methods of Synthesis of the Ketamine Analogs (2R, 6R)-kydroxynorketamine and (2S, 6S)-hydroxynorketamine for the Treatment of Pain and other Anxiety-related Disorders

This technology includes a method for synthesizing the ketamine analogs (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine that may be useful for the treatment of pain, depression, anxiety, and related disorders. The drug ketamine was first used as an anesthetic but was found to be an effective treatment in a range of conditions, including paint, treatment-resistant bipolar depression, and other anxiety-related disorders. However, the routine use of ketamine is hindered by unwanted side effects, including the potential for abuse.

Use of the Ketamine Metabolite (R,6R)-hydroxynorketamine in Depression

This technology includes the identification and use of a ketamine metabolite, (2R,6R)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone (HNK), for the treatment of depression. Ketamine is an NMDA receptor antagonist that exerts a rapid and sustained antidepressant and anti-suicidal effect. However, even low doses of ketamine has addictive and psychomimetic effects. The downstream metabolite, (2R,6R)-HNK, does not inhibit the NMDA receptor but recapitulates the antidepressant and anti-suicidal effect of ketamine.

High Affinity Monoclonal Antibodies Targeting Glypican-2 for Treating Childhood Cancers

Neuroblastoma is a rare pediatric cancer with approximately 1,000 new cases arising annually. Current therapies have a less than forty-five percent (45%), three-year survival rate which demonstrate a need for a more effective treatment against this disease. Glypican-2 (GPC2) is a cell surface protein that is preferentially expressed in pediatric cancers including neuroblastoma, which makes GPC2 an attractive candidate for targeted therapy. 
 

Antibodies to TMC1 Protein for Hearing Loss

This technology includes antibodies for TMC1 protein as a treatment for hearing loss. TMC1 is one of the common genes causing hereditary hearing loss. Our laboratory used synthetic peptides corresponding to the TMC1 protein to immunize rabbits. The resulting antisera were shown to bind to TMC1 protein expressed in heterologous expression systems. TMC1 protein is required for the transduction of sound into electrical impulses in inner ear sensory cells.

First in class Small Molecule Agonists of the mammalian Relaxin family receptor 1 (RXFP1) and use in treatment of cancer, fibrotic, and vascular disorders (HHS Ref No. E-145-2024-0-US-02)

It is well documented in literature that activation of RXFP1 by relaxin induces: 1) up-regulation of the endothelin system which leads to vasodilation; 2) extracellular matrix remodeling through regulation of collagen deposition, cell invasiveness, proliferation, and overall tissue homeostasis; 3) a moderation of inflammation by reducing levels of inflammatory cytokines, such as TNF-a and TGF-b; and 4) angiogenesis by activating transcription of VEGF.

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