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. 

Novel Dopamine D2 Receptor Antagonists and Methods of Their Use

Investigators at the NIH have identified a series of novel, small molecule antagonists of the dopamine D2 receptor. Among the dopamine receptor (DAR) subtypes, D2 DAR is arguably one of the most validated drug targets in neurology and psychiatry. For instance, all receptor-based anti-Parkinsonian drugs work via stimulating the D2 DAR, whereas all FDA approved antipsychotic agents are antagonists of this receptor. Unfortunately, most agents that act as antagonists of D2 DAR are problematic, either they are less efficacious than desired or cause multiple adverse effects.

Discovery of potent and selective D3 antagonist with alleviated hERG liability and optimized pharmacokinetic properties

One of the most challenging hurdles in creating safe and effective new medicines for many diseases is finding drugs that are effective without causing off-target cardiac issues, such as cardiac arrythmias. In collaboration with NIDA, scientists at NCATS have developed a series of novel and highly specific dopamine D3 receptor agonists and antagonists that have potential to target and treat Parkinson’s disease, Schizophrenia, Depression, and substance-use disorders including opioid addiction.

Systemic CRISPR Therapy for the Treatment of Inherited Diseases

This technology includes novel systemic adeno-associated virus (AAV)-mediated CRISPR gene therapy technology. While some diseases (e.g., retinal diseases) can be treated through local gene transfer, many diseases such as Duchenne Muscular Dystrophy (DMD) require systemic therapy. The CRISPR technology has two components, the Cas9 endonuclease, and the gRNA. To explore systemic CRISPR therapy, we co-delivered the AAV.Cas9 and AAV.gRNA vector to mdx mice, a mouse DMD model. Direct delivery to muscle yielded efficient gene correction.

Using FDA-approved Small Molecule Drug Reserpine and related compounds (especially Halofantrine) To Protect Photoreceptors In Inherited Retinal Degenerations And Age-Related Macular Degeneration

Summary: 

The National Eye Institute seeks research co-development partners and/or licensees for a therapy using an FDA-approved small molecule drug reserpine (and related compounds especially halofantrine) that prevents photoreceptor cell death in retinal degenerations.

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