Creation and Use of Kinetin Derivatives for Treating RNA Missplicing Diseases Such as Familial Dysautonomia

This technology includes the creation and use of compounds, including kinetin derivatives, that improve mRNA splicing in a cell for the treatment of disorders associated with misspliced mRNA, including familial dysautonomia (FD). FD, the best-known and most common member of a group of congenital sensory and autonomic neuropathies, affects neuronal development and is associated with progressive neuronal degeneration. This disease is caused by mutations in the splicing of intron 20 of the IKMKAP gene that results in a unique pattern of tissue-specific exon skipping.

Treatment of primary hyperoxalurias with small molecule lactate dehydrogenase inhibitors such as WO2018005807A1

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.

A Novel High-Throughput Assay for Identifying Zike Virus NS2B-NS3 Protease Inhibitors

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.

Process for Practical, Scalable, Commercially-viable Method for the Synthesis of Enantio-enriched Aminoalcohols, Including the Novel Antifungal VT-1129 Used to Treat Cryptococcal Meningitis

This technology relates to the discovery and development of a practical, scalable, and commercially viable method for the synthesis of the novel antifungal VT-1129. Cryptococcal meningitis (CM) is a fungal infection that is particularly prevalent in immune-compromised patients and can be treated by VT-1129. CM has a current estimated patient population of 1-1.25 million, predominately in sub-Saharan Africa and the developing world.

A Group of Compounds that Activate AMP-activated protein kinase (AMPK) that may Treat Niemann-Pick Disease Type C (NPC)

This technology relates to the identification and use of a group of compounds that activate the AMP-activated protein kinase (AMPK) and also effectively reduce lysosomal cholesterol accumulation in patients with Niemann-Pick disease Type C (NPC). Clinical trials are currently underway to determine the efficacy of beta-cyclodextrin in treating patients with NPC. A potential mechanism has been proposed indicating that beta-cyclodextrin activated AMP-activated protein kinase, leading to restoration of autophagy in cells from NPC patients.

Repurposed Use of the Alkaloids Emetine and Cephaeline to Treat Zika Virus Infection

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.

Novel ACRV1/ALK2 Inhibitors and Methods for Inhibiting BMP Signaling for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)

This technology includes the identification and use of novel ACRV1/ALK2 inhibitors for the treatment of fibrodysplasia ossificans progressiva (FOP), an autosomal-dominant rare disease that affects one person in every 1-2 million. FOP is characterized by malformation of the great (big) toes during embryonic development and by progressive heterotopic endochondral ossification (HEO) postnatally, which leads to the formation of a second skeleton of heterotopic bone.

Repurposing CDK Inhibitors for the Treatment of Zika Virus Infection

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.

Identification and Use of a Novel Functionally Selective GHSR1a Ghrelin Receptor Inhibitor, including NCGC00538279, for the Treatment of Food and Chemical Addiction

This technology includes a chemical series, including the NCGC00538279 compound, that selectively activates the GHSR1a G-protein pathway for calcium mobilization while only partially activating the beta-arrestin-2 translocation pathway. The resulting chemical series may be therapeutically valuable for addictive disorders. Activation of the GHSR1a G-protein pathway promotes production and secretion of multiple hormones, including insulin, growth hormone, and IGF1. Activation of the beta-arrestin-2 pathway stimulates dopamine production and may mediate addictive behaviors.

3D Vascularized Human Ocular Tissue for Cell Therapy and Drug Discovery

Degeneration of retinal tissues occurs in many ocular disorders resulting in the loss of vision. Dysfunction and/or loss of Retinal Pigment Epithelium Cells (RPE) and disruption of the associated blood retinal barrier (BRB) tissue structures are linked with many ocular diseases and conditions including: age-related macular degeneration (AMD), Best disease, and retinitis pigmentosa. Engineered tissue structures that are able to replicate the function of lost BRB structures may restore lost vision and provide insight into new treatments and mechanisms of the underlying conditions.