Penta-DMD Platform for Duchenne Muscular Dystrophy

Disease Background: Duchenne Muscular Dystrophy is a condition affecting the muscles that leads to progressive wasting of both skeletal and cardiac muscle. The causative factor is a mutation in the gene for the protein dystrophin with predominant insertions in the gene leading to frameshift mutations and to a lesser extent due to point mutations in the same gene. Dystrophin protein forms a part of protein complex that connects the muscle cytoskeleton with the extracellular matrix. The symptoms initiate with a difficulty to sit, stand, walk and difficulties with speech. The symptoms are visible from early childhood with children depending on support for locomotion. The disease progresses with difficulty in breathing leading to more severe complications. Gene therapy and exon skipping are recent advances in the treatment of this condition

Details on the Model: Pentagrit model of Duchenne Muscular Dystrophy is a mutant for the protein dystrophin. Zebrafish mutants for the dystrophin show muscle wastage pathology and difficulty in movements accompanied with decreased operculum movement. The gill apparatus is white or pale red unlike normal fish. The color decrease is observed due to lower level of oxygenation and blood supply to the fish. The disease progress with mortality due to breathlessness and in some cases, infection associated with poor locomotion and feed pattern. Dystrophin mutant fish also shows cognitive impairments observed as memory loss and seizures.