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.

Enhancing Activity of Bispecific Antibodies in Combination with Ibrutinib for the Treatment of Cancer

This technology includes the combination of a kinase inhibitor (specifically ibrutinib) with a bispecific antibody (specifically a CD19/CD3 bispecific antibody) to be used to treat cancer. CD19/CD3 bispecific antibodies (bsAbs) can be used to recruit endogenous T cells against CD19+ tumor cells via the formation of cytolytic synapses. lbrutinib, a BTK inhibitor, has been shown to normalize T cell dysfunction characteristic of CLL.

Antibody Targeting of Cell Surface Deposited Complement Protein C3d as a Treatment for Cancer

This technology includes monoclonal antibodies (mAb) that specifically and with high affinity bind the final complement components C3dg and C3d (subsequently referred to as C3d), which can be used to kill tumor cells that carry C3d on their cell surface. We show that tumor cells of patients treated with the therapeutic anti-CD20 mAb ofatumumab carry C3d on the cell surface and can bind and be killed by addition of anti-C3 mAbs. In contrast, further addition of more ofatumumab has only minimal effects.

A Neural Stem Line from a Niemann Pick C (NPC) Type 1 Patient for Therapy Development

This technology includes a neural stem cell (NSC) line derived from a Niemann Pick C (NPC) patient, aimed at advancing research and drug development for NPC, an inherited neurodegenerative disorder characterized by the accumulation of cholesterol in neurons. The NSCs, which serve as a crucial intermediate cell type, can be differentiated into any neuronal or glial cell of the brain or spinal cord under appropriate culture conditions. These cells originate from fibroblasts reprogrammed into induced pluripotent stem cells.

Neural Stem Cells from an iPSC Line Ubiquitously Expressing Green Fluorescent Protein for Basic Science Research and Cell Line Tracking

This technology involves neural stem cells (NSCs) derived from pluripotent stem cells (PSCs) that can differentiate into neurons and glia. The key feature of this technology is the CY2 EEF1A1 GFP iPSC line, which includes a green fluorescent protein (GFP) expressed under the EEF1A1 promoter, leading to its ubiquitous expression in cells. This characteristic makes the NSCs and the neural cells differentiated from this line exhibit green fluorescence. Such cells, when transplanted into animal models like mice and rats, can be easily tracked due to their fluorescence.

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.

Vascularized Thyroid-on-a-Chip for Personalized Drug Screening and Disease Modeling

This technology includes a micro-engineered “thyroid-on-a-chip” that combines human thyroid organoids with integrated micro-vasculature to replicate the gland’s native blood flow and 3-D architecture, enabling rapid, patient-specific drug screening. By permitting real-time perfusion of nutrients, hormones, and immune cells, the platform yields more physiologically relevant data than conventional static cultures or animal surrogates.

Use of Antihistamine Compounds for the Treatment of Hepatitis C Virus

The vast majority of people infected with Hepatitis C Virus (HCV) will have chronic infection. Over decades, this can lead to liver disease and liver cancer. In fact, HCV infection is the leading cause of liver transplants in the U.S. Several new drugs have recently come into the market that will likely change the HCV treatment paradigm. However, the effectiveness of these new drugs can vary depending on the HCV genotype. Thus, there is still the need for additional new therapeutics against HCV.

A Novel System for Producing Infectious Hepatitis C Virus (HCV) Virions and Development of a Novel Reporter System for Studying HCV Entry

HCV has infected an estimated 3% of the world population in whom viral infection persists for more than two third of the cases, often resulting in life-threatening complications. The standard of care (pegylated interferon alpha-2 plus ribavirin) is efficient in only 50% of treated patients, costly and has numerous side effects. In addition, viral resistance to newly developed drugs -- targeting viral protease or RNA polymerase -- has been described, but no vaccine is yet available.
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