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This technology includes a series of novel benzene-1,4-disulfonamides that activate TRPML1 receptor. The TRPML1 receptor is a lysosomal Ca2+ channel that has been shown to be involved in controlling lysosome functions, among then the maintenance of the integrity of the plasma membrane and the modulation of autophagosome-lysosome fusion. The improved ability of the receptor to deliver Ca2+ ions to the cytosol had been correlated with its capacity to modulate autophagy and lysosome exocytosis.

This technology includes a new Zika virus NS-1 assay which was used for a compound screen. Because the NS-1 protein is synthesized only in the Zika virus replication stage, the inhibition of NS-1 protein level by compounds determined in this NS-1 assay indicates the inhibition of Zika virus replication in human cells. A total of 256 compounds have been identified as active compounds that inhibited NS-1 production in human cells that have the potential to be developed as new therapeutics for the treatment of infection with Zika virus.

This technology includes compounds that improve endoplasmic reticulum-lysosomal trafficking and normalizes the Niemann-Pick type C (NPC) phenotype in assays using NPC1 patient cells, which can be used for the treatment of NPC, other lysosomal storage disorders, and potentially other neurodegenerative disorders. NPC is a rare neurodegenerative lipidosis caused by mutations in NPC1 or NPC2 genes, and characterized by the accumulation of cholesterol and glycolipids in the late endosomes and lysosomes. Currently there is no FDA-approved treatment for this devastating neurodegenerative disease.

This technology includes the development of devices capable of real-time evaluation of metabolite levels for the treatment of numerous metabolic disorders, including hyperammonemia and aminoacidopathies. Currently, the monitoring of metabolite levels is done in a hospital setting with specialized mass spectrometry instrumentation. As a consequence, susceptible patients who are undergoing a crisis need to visit the hospital for testing to determine if there is a metabolite disturbance.

This technology includes the use of novel lactate dehydrogenase (LDH) inhibitors, including WO2018005807A1, for the treatment of primary hyperoxalurias (PHs). PHs are rare autosomal recessive disorders caused by overproduction of oxalate, leading to recurrent calcium oxalate kidney stone disease, and in some cases end-stage renal disease. One potential strategy to treat PHs is to reduce the production of oxalate by diminishing the activity of LDH, the proposed key enzyme responsible for converting glyoxylate to oxalate.

This invention includes a novel high-throughput assay to identify orthosteric inhibitors blocking the Zika virus NS2B-NS3 protease. Pathogenic flaviviruses, including Zika, require the NS2B-NS3 protease for viral replication. There is currently an unmet need for specific antiviral therapeutics against the Zika virus. Preliminary screening using the NCGC Pharmaceutical Collection library identified a group of drugs including temoporfin, erythrosin B, niclosamide, and nitazoxanide that can significantly inhibit the interactions between NS2B and NS3.

This technology includes the use of two related compounds, Emetine and Cephaeline, as a potent inhibitor of the Zika virus (ZIKV). Emetine and it's analog Cephaeline were identified in a high-throughput assay aimed at identifying anti-ZIKV compounds. Both Emetine and Cephaeline are potent inhibitors of ZIKV infection in cell culture, and Emeline is a potent inhibitor of ZIKV infection in a live mouse model.

This invention includes the discovery and use of a group of CDK inhibitors that were found during a drug repurposing screen designed to find compounds that inhibit Zika virus caused cell death. The identified CDK inhibitors have all previously been used in clinical trials for other diseases, potentially reducing the long time course needed for new drug discovery and development.

Methylmalonic Acidemia (MMA) is a metabolic disorder characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat by-products resulting in seizures, strokes, and chronic kidney failure. A significant portion of MMA cases stem from a deficiency in a key mitochondrial enzyme, methylmalonyl-CoA mutase (MUT), required to break down amino acids and lipids. Currently, there are no treatments for MMA and the disease is managed primarily with dietary restriction of amino acid precursors and liver-kidney transplantation in severe cases.

This technology includes two human fibroblast cell lines to be used to study the defects in GBA1 gene and protein and to screen small molecules for involvement in Gaucher disease. Glucocerebrosidase (GBA1 or GCase or beta-glucosidase) is a lysosomal enzyme, responsible for breakdown of a fatty material called glucocerebroside (or glucosyl ceramide). Deficiency or malfunction of GBA1 leads to the accumulation of insoluble glucocerebrosides in tissues, which is a major symptom of Gaucher disease.