Penta-GD Platform for Gaucher disease

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Disease Background: Gaucher Disease is a lysosomal storage disorder commonly classified under chronic lysosomal storage disorders. Lysosomes’ primary function is the digestion of nutrients and waste using hydrolytic enzymes. In individuals with lysosomal storage disease a deficiency of lysosomal enzymes leads to an abnormal accumulation of complex carbohydrates in various regions of the body leading to the pathophysiology. Accumulations could be in the arteries, joints, ears, skin, skeleton, eyes, and teeth and within the vital organs such as liver, spleen, bone marrow, blood and central nervous system. In the case of Gaucher disease the deficiency in glucocerebrosidase leads to accumulation of glucocerebroside in the macrophages leading to accumulation of Gaucher cells primarily in the spleen, liver and bone marrow, causing organ inflammation followed by dysfunction and mortality.

 

Details on the Model: Pentagrit zebrafish model of Gaucher disease is a GBA mutant that displays weak motor behavior along with reduced bone density. The fish displays swollen peritoneal region due to enlarge liver and spleen. Patterns of hemorrhage are visible in the skin along with anemic blood profile, leading to premature mortality.