March 21, 2013
Parent Project Muscular Dystrophy (PPMD)
University of Minnesota
a grant for
to develop a therapeutic approach for
Duchenne muscular dystrophy
(Duchenne) using a new type of "adult-derived" stem cell called "induced pluripotent stem cells" or "iPSCs." iPSCs can be created from non-controversial sources like skin, have the ability to multiply indefinitely, and can be coaxed to become many different kinds of tissue types.
Previously, Dr. Perlingeiro's group demonstrated that skin cells from donor mice that lack dystrophin could be converted into iPSCs, and then converted again into muscle stem cells with the mutation corrected using a modified viral carrier. When these corrected mouse stem cells were transplanted into recipient mice that lacked dystrophin, the mice showed improved muscle strength.
Now Dr. Perlingeiro will repeat this process with funding from PPMD, this time using human skin cells from donors with Duchenne and using a safer method of correcting the dystrophin deficiency that does not rely upon random integration. The goal is to start laying the groundwork for an FDA-approved stem cell treatment for Duchenne.
"Translating results in mice to treatments in humans is never straightforward," said Dr. Perlingeiro. "Support from the Parent Project will be tremendously beneficial at this stage in the development of stem cell therapies for muscular dystrophy."
Since the mid-1990s, researchers have investigated repairing muscle lost to muscular dystrophy with various types of cells, usually from an unaffected donor whose cells have a normal supply of dystrophin. Key challenges have included producing and purifying enough stem cells to transplant, getting cells to migrate into the diseased muscle, and then getting the donor cells to survive long enough to engraft and build healthy new muscle without being attacked by the immune system. By using iPSCs, Dr. Perlingeiro's approach should theoretically allow an infinite supply of healthy muscle stem cells to be generated from a single small skin sample from a person with Duchenne. And because a person's own cells, corrected for the dystrophin mutation, would ultimately be used for treatment, the potential for the recipient's immune system to reject the new cells is reduced.