Scalability and Safety Studies in Clinical-Grade Pluripotent-Derived Myogenic Progenitors for Therapeutic Application in DMD
Abstract
There has been tremendous excitement for the therapeutic potential of skin reprogrammed induced pluripotent stem (iPS) cells in treating genetic diseases. This application builds on our successful studies developing such cell therapies specifically in mouse models of Duchene muscular dystrophy (DMD). Our goal now is to develop a current good manufacturing practices (cGMP)/clinically friendly protocol for the generation of iPS cell-derived therapeutic muscle progenitor cells. Our research group has pioneered a method that uses the natural regulators of muscle development, the Pax3 and Pax7 genes, to recapitulate muscle development in the Petri dish, which leads to highly efficient generation of therapeutic muscle progenitor cells. Transplantation of mouse and human pluripotent stem cell-derived muscle progenitor cells in mouse models of DMD results in muscle fiber and stem cell engraftment that is accompanied by improvement in muscle force generation. Based on these encouraging findings, we feel it is time now to begin the groundwork that will enable the future testing of this approach in humans. This proposal aims to optimize strategies for the purification (using surface markers), scalability, safety, and manufacturing of human pluripotent stem cell-derived muscle progenitors, critical aspects to enable the therapeutic application of these cell preparations. Once this is achieved and validated, we will be in a strong position to begin Investigational New Drug (IND) filing, and a Phase 1 safety trial. The intent of this cell product is to replace diseased muscle with normal functional muscle fibers as well as muscle stem cells, which have the potential to provide long-term therapeutic effect in DMD, as well as other devastating types of muscular dystrophies, muscle wasting conditions, and injuries resulting in loss of muscle or muscle function. The support from the Department of Defense will be essential to move this research program forward.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710659
Entities
People
- Rita Perlingeiro
Organizations
- United States Army
- University of Minnesota