Use of Repurposed Compounds for the Treatment of Alzheimer’s Disease

There are no effective treatments for Alzheimer’s disease (AD), a progressive brain disease that slowly destroys a person’s memory, cognitive skills and ability to carry out the simplest tasks. AD affects more than 5 million individuals in the United States and ranks as the sixth leading cause of death. The ε4 allele of the apolipoprotein-E (APOE) gene is the strongest genetic risk factor for sporadic or late-onset AD. Heterozygous carriers of the ε4 allele are at three-to-four times greater risk; homozygous carriers are at ten times greater risk.

Fatty Acid Derivatives and Their Use for the Treatment and Prevention of Autoimmune, Inflammatory, and Pain Disorders

The discovery and selection of suitable compounds for the treatment and prevention of autoimmune, inflammatory, and pain disorders is a significant challenge. Researchers at National Institute of Aging (NIA) mitigated this issue. They discovered and synthesized numerous novel fatty acid derivatives (novel small molecules) that may ameliorate these conditions and provide treatment options for these disorders. In a relevant rat model, the fatty acid derivatives developed by NIA demonstrated:

Thalidomide Analogs that Inhibit Inflammation and Angiogenesis

Thalidomide and its close analogs (lenalidomide and pomalidomide) are widely used to treat a variety of diseases, such as multiple myeloma and other cancers as well as the symptoms of several inflammatory disorders. However, thalidomide is known for its teratogenic adverse effects when first clinically introduced in the 1950s, and is associated with drowsiness and peripheral neuropathy. Hence, there is intense interest to synthesize, identify and develop safer analogs. 

Novel Human Islet Amyloid Polypeptides as Alzheimer’s Disease Biomarkers and Inhibitors of Amyloid Formation

Over 34 million Americans are living with diabetes. An estimated 6.5 million Americans are living with Alzheimer’s disease (AD) and type 2 diabetes mellites (T2DM). Amyloidosis due to aggregation of amyloid-β is key pathogenic event in AD, whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islet leads to β-cell dysfunction. A hallmark feature of T2DM is the accumulation of islet amyloid polypeptide fibrils in pancreatic islets. Such accumulations form amyloid plaques and cause apoptosis of -cells of islets. 

Engineered Biological Pacemakers

The National Institute on Aging's (NIA) Cellular Biophysics Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize biological pacemakers.

A common symptom of many heart diseases is an abnormal heart rhythm or arrhythmia. While effectively improving the lives of many patients, implantable pacemakers have significant limitations such as limited power sources, risk of infections, potential for interference from other devices, and absence of autonomic rate modulation.

Topoisomerase III (TOP3) Inhibitors and Antiviral Compounds based on Cyanine Dyes

Topoisomerase 3B (TOP3B) is the only topoisomerase that can act on RNA as well as DNA, and thus has been a target of interest for the development of cancer therapies and RNA viral infection therapies. In the context of cancer, TOP3B is not an essential gene, but a subset of cancer cells with pre-existing genome instability are particularly vulnerable to the inactivation of TOP3B. While inhibitors for other topoisomerases are among the most potent and widely used anticancer agents, there are no known inhibitors of TOP3B.

Human iPSC-Derived Mesodermal Precursor Cells and Differentiated Cells

Cells, cell culture methods, and cell culture media compositions useful for producing and maintaining iPSC-derived cell lines that are of higher purity and maintain cell type integrity better than current iPSC-derived cell lines are disclosed. Human induced pluripotent stem cells (hiPSCs) can be generated by reprogramming somatic cells by the expression of four transcription factors. The hiPSCs exhibit similar properties to human embryonic stem cells, including the ability to self-renew and differentiate into all three embryonic germ layers: ectoderm, endoderm, or mesoderm.

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.

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.
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