CHOP Scientist Shares New Grant to Restore Vision Using Stem Cell Therapy

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A CHOP researcher is working to manipulate stem cells to restore vision in genetic cases of blindness. Under a new five-year, $6.9 million grant from the National Eye Institute (NEI) focused on bold, innovative programs for blinding conditions, a research team co-led by John H. Wolfe, PhD, VMD, a Stokes Investigator at the Children’s Hospital of Philadelphia Research Institute, will treat blind dogs, with the goal of establishing the scientific groundwork for new treatments in people.

Wolfe is one of three co-principal investigators of the NEI grant, along with Drs. William A. Beltran of the Perelman School of Medicine at the University of Pennsylvania and David M. Gamm of the University of Wisconsin-Madison. The grant, "Retinal Disease Models for Translational Photoreceptor Replacement,” is part of the NEI’s Audacious Goals Initiative for Regenerative Medicine, aimed at catalyzing new treatments for human blinding conditions. Wolfe and Beltran are both on the faculty of the School of Veterinary Medicine at the University of Pennsylvania.

The research team uses cell cultures and animal models of eye disease to understand root causes of each disease, investigate disease progression, and test potential tools and therapies before applying them to people.

In his CHOP laboratory, Wolfe has long investigated gene therapy approaches for neurological disorders, including stem cell approaches to treating lysosomal storage diseases, caused by inherited defects in the lysosomal enzymes, part of the cell’s waste recycling system. He will collaborate with Beltran, Gamm and colleagues to develop stem cell strategies for treating degenerative eye diseases. The new grant addresses a hurdle in potential gene therapy: the fact that replacing or correcting faulty genes in light-sensing must be done in living retinal cells — the very cells that many blinding diseases progressively destroy.

To overcome this problem, the team plans to take cells from adult animals, reprogram them into stem cells, culture the stem cells in the laboratory into retinal photoreceptor cells — and finally transplant those cells into the retinas of dogs with vision loss. After the scientists work on developing the cells and testing the best method of transferring them into the retina, they will analyze the resulting neural connections to determine how well the implanted cells function. “Our ultimate goal is to build the foundation for cell-based treatments to restore vision to people who have already lost key vision cells,” says Wolfe.

For more about this work, see this press release from the Penn Vet School.

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