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.

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.

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.

Novel Regulatory B cells for Treatment of Cancer and Autoimmune Disease

The manner by which cancers evade the immune response is not well-understood. What is known is that the manner is an active process that regulates immune responses employing at least two types of suppressive cells, myeloid-derived suppressive cells and regulatory T cells (Tregs), a key subset of CD4+ T cells that controls peripheral tolerance to self- and allo-antigens. Tregs are considered to play a key role in the escape of cancer cells from anti-tumor effector T cells.

Immunogenic Antigen Selective Cancer Immunotherapy

Melanoma is a particularly aggressive form of cancer primarily caused by over-exposure to sunlight.  Although melanoma can strike at any age, the malignancy disproportionately impacts persons of advanced age, as these individuals often have decades of repeated exposure to harmful levels of ultraviolet radiation.  Scientists at NIH among others have clarified the link between advanced melanoma and other malignancies and expression of SPANX-B.