University of Colorado

Kunhua Song

Timothy McKinsey

Pilar Londono

Yuanbiao Zhao

Congwu Chi

Yingqiong Cao

The disclosed technology includes methods of treating Danon disease, for example correcting genetic mutations in the LAMP-2 gene and ameliorating at least one Danon disease phenotype, for example defective LAMP-2B-mediated autophagy. In some implementations, the disclosed methods include editing a mutated form of the LAMP-2 gene in a patient in need thereof. In some implementations, editing the mutated form of the LAMP-2 gene may include use of a CRISPR editing technique targeted to the mutated form of the LAMP-2 gene. As a result, mutated LAMP-2 proteins in mammalian subjects may be restored in at least some of the affected cells, for example cardiomyocytes.

Methods of treating Danon disease

Pro-fibrotic signaling potently antagonizes cardiac reprogramming. Inhibition of pro-fibrotic signaling using small molecules that target the transforming growth factor-&#x3b2;/SMAD, or Rho kinase leads to conversion of approximately 60% of fibroblasts into beating cardiomyocytes. Conversely, over-activation of these pro-fibrotic signaling networks inhibits cardiac reprogramming. Using the disclosed methods, fibroblasts are converted to spontaneously contracting cardiomyocytes in less than two weeks.

Growing community of inventors

Centennial, CO, United States of America

Kunhua Song