Modulating Autophagy as a Treatment for Lysosomal Storage Diseases

Researchers at NIAMS have developed a technology for treatment of lysosomal storage diseases by inhibition of autophagy. Pompe disease is an example of a genetic lysosomal storage disease caused by a reduction or absence of acid alpha-glucosidase (GAA). Patients with Pompe disease have a lysosomal buildup of glycogen in cardiac and skeletal muscle cells and severe cardiomyopathy and skeletal muscle myopathy. Treatment of Pompe disease by GAA enzyme replacement therapy is quite ineffective for the skeletal muscle myopathy.

DLX3-floxed mice (DLX3f/f) for Use in Drug Development and In Vivo Research Studies for Ectodermal Dysplasia Disorders

This technology includes the creation of DLX3-floxed mice, specifically designed for conditional deletion of the DLX3 gene via Cre-mediated recombination. This innovative approach aims to develop mouse models for studying ectodermal dysplasia disorders. Ectodermal dysplasias are a diverse group of genetic conditions affecting the development of ectodermal structures, including hair, teeth, and bones. The DLX3f/f mice are particularly valuable for modeling specific disorders such as Tricho-dento-osseous syndrome (TDO), Amelogenesis Imperfecta (AI), and Dentinogenesis Imperfecta (DI).

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.

Generation of AAVS1 and C13 “Safe Harbor” Transcription Activator-life Effector Nucleases (TALENs) for Drug Screening or Gene Therapy Development

This technology includes AAVS1 and C13 “safe harbor” transcription activator-life effector nucleases (TALENs) for drug screening or gene therapy applications. TALENs are engineered sequence-specific DNA endonucleases that can significantly enhance genome-editing efficiency by >100-1000 folds. “Safe harbor” such as AAVS1 safe harbor and C13 safe harbor is genome locus that allows robust and persistent transgene expression with no or minimal interference of endogenous gene expression and cell properties.

Novel ApoC-11 Mimetic Peptides That Activate LPL for the Treatment of ApoC-11 Deficiency and Hypertriglyceridemia

This technology includes a new class of synthetic peptides that activate Lipoprotein Lipase (LPL), a key plasma enzyme that lowers triglycerides. Mutations in apoC-II is a genetic cause of severe hypertriglyceridemia, which can lead to cardiovascular disease and pancreatitis.

Mouse Models of Cryopyrin-Associated Periodic Syndrome (CAPS) for Drug Discovery

This technology includes mouse models that express versions of mouse cryopyrin protein containing mutations associated with human CAPS disease. We engineered mutations associated with three specific CAPS phenotypes (familial cold autoinflammatory syndrome (FCAS); Muckle-Wells syndrome (MWS); and neonatal onset multisystem inflammatory disease (NOMID)) into the mouse cryopyrin gene (called Nlrp3) to examine the roles of IL-1 β and related cytokines, and better characterize inflammasome functions.

Novel Methods for Reducing Inflammation and Treating Diseases such as Parkinson's and Alzheimer's Disease

Microglia activation leads to inflammation mediated dopaminergic degeneration in the brain of patients with Parkinson and Alzheimer's Disease. Thus Identification of drugs that reduce microglia activation could prevent or reverse neuronal degeneration in these diseases and other degenerative CNS disorders.

ApoA-1 Mimetic Peptides Promoting Lipid Efflux from Cells for Treatment of Vascular Disorders

This invention involves ApoA-1 mimetic peptides with multiple amphipathic alpha-helical domains that promote lipid efflux from cells and are useful in the treatment and prevention of dyslipidemic, inflammatory and vascular disorders. IND-enabling studies for one of the peptides, named Fx-5A, are completed in preparation for an IND filing at the FDA, to be followed by a Phase I clinical trial planned for 2017.
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