Driving Life-Changing Discoveries

Curing congenital blindness with a single injection of genes. Modifying cancer cells to actually fight the disease within a child’s body. Using a child’s skin cells to better understand mental illness.

These efforts and more are currently underway at The Children’s Hospital of Philadelphia’s Raymond G. Perelman Center for Cellular and Molecular Therapeutics (CCMT), recently named in recognition of Perelman’s transformative $50 million gift, part of which will be used to fuel the center’s research.

It is one of the few programs in the world to focus on applying gene therapy to pediatric diseases. In recent years, the center has made headlines with innovative treatments for retinal blindness, hemophilia B and childhood leukemia. The key has been the development of a new generation of vectors, viruses that CCMT engineers use to correct a malfunctioning sequence of DNA.

In April 2014, Beverly Davidson, PhD, an internationally known expert in gene therapy, was named director of the CCMT, replacing its founding director and another renowned gene therapy expert, Katherine High, MD. High left to lead Spark Therapeutics, a for-profit gene therapy company recently spun off by CHOP and designed to commercialize the kind of breakthroughs that have come from High’s decades of research.

Davidson and her team at the CCMT are focused on making discoveries and taking them through the beginning phases of the clinical trials process, which tests therapies on small groups of patients to evaluate safety and efficacy. For research discoveries it funds, Spark Therapeutics may then pick up the baton, taking viable gene therapies into larger late-stage clinical trials and, hopefully, FDA approval.

The first fruit of this relationship between the CCMT and Spark concerns a treatment for a form of inherited blindness that has the potential to be the first FDA-approved gene therapy in the United States. Because of very promising early clinical evidence — patients who were almost totally blind had much of their sight restored — the FDA granted it “breakthrough therapy” designation, a status that speeds the development and review of investigational therapies for serious or life-threatening conditions.

And the CCMT has many more studies in the clinical trials pipeline. Davidson’s group aims to treat inherited brain conditions such as Batten disease and related diseases known as lysosomal storage disorders. These diseases, caused by the lack of an enzyme, result in a buildup of toxic waste products in the brain that causes progressively severe brain damage. There is no cure, and the diseases are fatal. CCMT investigators are developing gene delivery strategies that provide enzyme replacement to the brain for therapy.

Before her arrival at CHOP, Davidson was the Roy J. Carver Biomedical Research Chair, associate director of the Center for Gene Therapy and vice chair for the Department of Internal Medicine at the University of Iowa, where she developed novel methods to deliver therapeutic genes to the central nervous system. Her research team, most of whom followed her from Iowa to CHOP, has completed proof-of-concept studies in animal models with either adult- or childhood-onset neurological deficits such as lysosomal storage disorders, Huntington’s disease and the spinocerebellar ataxias, and they are working to advance these to humans.

In addition to the growing translational neuroscience at the CCMT, the center continues its strength in developing novel therapies for hematologic disorders through the investigations of Valder Arruda, MD, PhD; Rodney Camire, PhD; Paris Margaritis, DPhil; and Denise Sabatino, PhD. The Human Hematopoietic Stem Cell Center of Excellence, led by Paul Gadue, PhD, and Deborah French, PhD, helps investigators from these and other fields understand the basic biology of disorders in addition to advancing cell-based therapies through their own research efforts.

“It’s very invigorating and exciting to be here,” says Davidson. “There are so many resources at CHOP and so many enthusiastic investigators working to apply these discoveries to humans. The Perelman gift will play an enormous role in advancing these therapies.”