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The molecular imaging technique of positron emission tomography (PET) is an increasingly important tool in biomedical research and in drug discovery and development. Many small molecule drugs and potential PET radiotracers carry trifluoromethyl (CF₃) groups. Because CF₃ groups are generally considered to be metabolically stable, there is a strong interest in developing drugs with these groups.

This technology is directed towards a potential treatment for a new disease, CHAPLE (Complement Hyperactivation, Angiopathic thrombosis, and Protein-Losing Enteropathy), identified by NIAID researchers. CHAPLE is associated with GI symptoms and vascular thrombosis and is caused by loss-of-function variants in the gene encoding the complement regulatory protein CD55. The disease is caused by enhanced activation of the complement pathway and complement-mediated induction of intestinal lymphangiectasia and protein-losing enteropathy.

Multiple sclerosis (MS) is an autoimmune disease caused by activated autoimmune T lymphocytes in patients resulting in inflammatory demyelination in the central nervous system. Current treatments are focused on functional control of these activated autoimmune T cells, but these treatments are non-specific T cell inhibitors and have serious, sometimes fatal side effects. A specific therapy aimed at eliminating these autoimmune T cells through restimulation-induced cell death (RICD) could cure the disease and overcome the fatal side effects of current therapies.

Niemann-Pick Disease, type C (NPC) is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutation of NPC1 causes intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue. Thus, NPC patients generally present with hepatosplenomegaly (enlargement of liver and spleen) and neurological degeneration.

This technology includes a method for creating functional, brain region-specific neural spheroids that can be used for disease modeling and therapeutic testing of compounds for neurological diseases. The developed protocol uses somatic cells, including iPSC-derived neurons, as well as astrocytes using means such as 96- or 384-well ultra-low attachment round-bottom plates. Spheroids have been generated using this method that model brain regions such as the ventral tegmental area and prefrontal cortex, which are implicated in Parkinson’s and Alzheimer’s disease.

This technology includes the use of autophagy upregulators such as ML246/metarrestin to counteract the tolerance that can build up through the therapeutic use of cannabinoids. Long-term administration of cannabinoids rapidly introduces tolerance and physical dependence, limiting its medical use and may lead to addiction and withdrawal symptoms. Cannabinoids mediate their effect by binding to and activating the cannabinoid receptor 1 (CNR1/CB1). Chronic exposure leads to CNR1 being targeted for degradation through a process of autophagy.

This technology includes the identification and use of small molecules to rescue cells undergoing ferroptosis, a type of programmed cell death. These small molecules can be used as treatments in situations where epithelial cells are being damaged, including respiratory disorders, brain injury (including traumatic brain injury), renal injury, radiation-induced injury, and neurodegenerative disorders. Ferroptosis is a type of programmed cell death that is triggered by an increased presence of oxidants.

This invention includes the generation and use of two polyclonal antibodies that specifically recognizes the phosphorylation site pThr707 of Neuroligin 4 and pThr739 of Neuroligin 1. A peptide of the site around the phosphorylation site was generated and injected into rabbits to create an immune response. Serum was collected from the rabbits that was then affinity purified. The specificity of the resulting polyclonal antibodies was then determined using biochemical techniques.

This invention is a novel statistical method for automatically detecting lesions in cross-sectional brain magnetic resonance imaging (MRI) studies. OASIS uses multimodal MRI from one image acquisition session and produces voxel-level probability maps of the brain that quantifies the likelihood that each voxel is part of a lesion. Binary lesion segmentations are created from these probability maps using a validated population-level threshold. In this application, fluid attenuated inversion recovery (FLAIR), proton density (PD), T2-weighted, and Tl-weighted volumes were used.

This technology includes the compositions and methods for inhibiting PIN1 for the treatment of disorders characterized by elevated PIN1 levels (e.g., immune disorders, proliferative disorders, and neurodegenerative disorders) with small molecules. Pin1 dysregulation has been associated with a number of pathological conditions. In particular, PIN1 has been shown to promote oncogenesis by modulating several oncogenic signaling pathways and its overexpression has been shown to correlate with poor clinical outcome.