Variations in genomics and resultant biochemical cascades contribute to health and disease and can be ancestry-specific. We initiated a study to investigate the incidence of four Lysosomal Storage Disorders (LSDs) in a cohort of mostly urban-dwelling African Americans, compared to previous work primarily in Caucasians (and Ashkenazi Jews). LSDs are inherited genetic disorders that result in the functional absence or deficiency of specific lysosomal enzymes and subsequent accumulation of their substrates in lysosomal compartments...

Deficiency of the lysosomal enzyme, β-glucocerebrosidase, and accumulation of its substrate in cells of the reticuloendothelial system affects multiple organ systems in patients with Gaucher disease (GD). Lipid laden macrophages turn into Gaucher cells (GC) which are the pathological characteristic of GD. GC focally accumulate in the liver, spleen and at extraosseous sites to form benign lesions called Gaucheromas. Gaucheromas pose diagnostic and therapeutic challenges...

Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells...

The knowledge of individual response to a therapy, which can be assesed by in vitro screening, is essential for the development of therapeutics. Chaperone therapy is based on the ability of small molecules to fold the mutant protein to recover its function. As a novel approach for the treatment of Gaucher disease (GD), ambroxol was recently identified as a chaperone for GD, caused by the pathogenic variants in GBA gene, resulting in lysosomal enzyme glucocerebrosidase (GCase) deficiency...

The major cellular clearance pathway for organelle and unwanted proteins is the autophagy-lysosome pathway (ALP). Lysosomes not only house proteolytic enzymes, but also traffic organelles, sense nutrients, and repair mitochondria. Mitophagy is initiated by damaged mitochondria, which is ultimately degraded by the ALP to compensate for ATP loss. While both systems are dynamic, and respond to continuous cellular stressors, most studies are derived from animal models or cell based systems, which do not provide complete real time data about cellular process involved in progression of lysosomal storage diseases...

NCATS // Thearapeutics for Rare and Neglected Disease Division of Pre-Clinical Innovation More Info

Duke University More Info

University of Maryland School of Medicine More Info

NIH/ NCATS Global Rare Diseases Patient Registry Data Repository (GRDR) More Info

Shaare Zedek Medical Center in Jerusalem More Info

NYU Langone Medical Center More Info

Université De Sherbrooke, Division of Genetics More Info