Principal investigator: Conrad Weihl (WashU Neurology)
Collaborator: Jan Bieschke (formerly WashU Biomedical Engineering)
Autosomal dominantly inherited mutations in the gene DES, which encodes the desmin protein, lead to devastating protein aggregate myopathies with premature death. Our proposal adopts a novel pathomechanistic paradigm that has not been investigated in skeletal muscle diseases associated with protein accumulation. Specifically, we will investigate the role of templated protein conversion in skeletal muscle. In addition, we will explore whether prion like protein transmission can occur from myofiber to myofiber. Finally, one mechanism for the phenotypic pleiotropy may relate to distinct protein aggregate conformations similar to those seen in neurodegenerative disorders. These studies will enable novel therapeutic interventions and diagnostic testing that has not been considered in these rare degenerative myopathies.
Niraja Kedia, Khalid Arhzaouy, Sara K. Pittman, Yuanzi Sun, Mark Batchelor, Conrad C. Weihl, and Jan Bieschke. “Desmin forms toxic, seeding-competent amyloid aggregates that persist in muscle fibers”. PNAS first published August 1, 2019.
Updated August 2019
Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty on this team, click below.