Dysferlinopathy's Accelerating affect on Differentiation Within the Patient

Skylar Worster and Michaela Mancuso

Abstract:
Our lab had the opportunity to explore and identify therapeutic options for dysferlinopathy which affects roughly 1 in every 200,000 people. There are currently no treatments for this disease, and very little corporate attention due to its rarity. Muscular dystrophy is caused by a misfolding of dysferlin, which causes an inability of cell membrane repair in muscle cells. This causes the patients to be wheelchair bound on average by the age of 30. Our lab has found evidence that the disease also causes faster maturation of affected cells, depleting the patients' stem cells as well as inhibiting their mature cell's repair. Our recent experiments confirmed these findings. Our hypothesis was that the quicker differentiation was due to an external factor, meaning it would increase the maturation of healthy cells growing nearby the mutated ones in the body, which would increase disease progression. We also predicted that these matured cells would be underdeveloped compared to those that matured at an appropriate speed, as analyzed by the amount of nuclei within the adult myofibers, which could mean that adult muscle fibers in the patient are underdeveloped as compared to a healthy individual. We explored these predictions as well as explored whether this effect was due to an internal or external factor, by co-culturing wildtype and mutated cell types as well as mixing the supernatant media between the two mono cultures.