A Translational Pathway Toward a Clinical Trial Using the Second-Generation AAV Micro-Dystrophin Vector
Principal Investigator:
DUAN, DONGSHENG
Institution Receiving Award:
MISSOURI, UNIVERSITY OF, THE CURATORS OF THE
Program:
DMDRP
Proposal Number:
MD130014
Award Number:
W81XWH-14-1-0302
Funding Mechanism:
Investigator-Initiated Research Award
Partnering Awards:
Award Amount:
$800,799.00
Period of Performance:
9/1/2014 - 12/31/2017
PUBLIC ABSTRACT
Duchenne muscular dystrophy (DMD) can be caused by thousands of different mutations in the dystrophin gene. Replacing the mutated gene with a functional microgene offers a one-size-fits-all therapy. Several dozens of first-generation microgenes have been shown to reduce muscle disease in mdx mice. However, early attempts in DMD dogs and human patients have failed to reproduce the success in mice. Recent studies suggest that there may exist several inherent structural defects in the first-generation microgene. We have now engineered the second-generation micro-dystrophin AAV vector. In the new vector, all known deficiencies were corrected. We have tested a canine version of the second-generation vector in adult dystrophic dogs and found it greatly reduced muscle disease and significantly improved muscle function. We propose to generate the human version of the vector and confirm its function in adult DMD dogs in a single muscle and then in whole body muscles. The validated human version vector will be ready for use in clinical trials. |
