PPMD Grants to Promote Gene Therapy for Heart Disease and Patient Outcomes Research

Parent Project Muscular Dystrophy (PPMD) has awarded two grants, one to further development of a gene therapy to prevent heart failure linked to Duchenne (DMD) and Becker muscular dystrophy (BMD), and another to create better measures of treatment responses in DMD clinical trials.

PPMD, a nonprofit organization leading the fight against DMD, awarded  $1 million to the professor and researcher H. Lee Sweeney, PhD, and his team at the University of Florida to continue developing gene therapies to address the causes of heart failure in Duchenne and Becker MD.

The grant is part of PPMD’s Cardiac Initiative, which draws on contributions from the Duchenne community, as well as the support of other Duchenne families and foundations.

For people with Duchenne, cardiac disease is a great concern. The absence of dystrophin contributes to a progressive deterioration of the heart’s muscle, leading to dilated cardiomyopathy (DCM).

In this disease, the muscle and chambers of the heart begin to dilate and can reach a point where the muscle cannot contract enough to pump blood well. As heart muscle weakens, heart failure can occur.

The funding will support the development of a heart-specific gene therapy using viral vectors (AAV vectors) to deliver two genes engineered to correct calcium handling and prevent the malfunction of mitochondria (the cell’s energy powerhouses) in the heart of Duchenne and Becker patients.

Sweeney and his team have been studying what happens in the heart during DMD, and found there is a calcium overload straining the organ. They have been treating animal models with the potential gene therapy, so far with positive results.

If successful, the therapy could treat the heart in a way that is independent of, or complementary to, micro-dystrophin based gene therapy.

“Heart issues don’t just affect some people with Duchenne; they affect ALL people with Duchenne. And while we have improved cardiac care in Duchenne, we still need treatments that repair our children’s hearts, ” PPMD’s president and CEO, Pat Furlong said in a press release. Furlong lost both of her sons to heart failure as a result from DMD.

“Chris and Patrick died of heart failure, so the heart is at the center of Duchenne for me,” Furlong added. “That’s why I am extremely proud to announce this $1 million investment into a gene therapy with the potential to heal the hearts of our loved ones. I am grateful to Dr. Sweeney and the amazing team at University of Florida, as well as the families in our community who believe in our mission and gave generously to help fund the fight to end Duchenne.”

PPMD is also partnering with Duchenne UK to fund a project to create a set of highly sensitive and validated patient-reported outcomes (PROs) for use in Europe and the U.S.

The $200,000 grant was awarded to Chad Heatwole, MD, MS, the project’s leader and a neuromuscular clinician at the University of Rochester. Its goal is to develop outcome measures for clinical trials that are able to better capture treatment benefits from a patient and caregiver perspective.

Building on their experience in developing health indices for other diseases, Heatwole and his team will conduct a series of interviews with patients from Europe and the U.S. to identify relevant symptoms, and develop a comprehensive set of patient-reported outcomes according to regulatory guidelines from the FDA (in the U.S.) and EMA (in Europe).

“We believe that incorporating the voice of the patient through PROs is an extremely powerful tool to support and accelerate drug development. We are grateful to be working with the Duchenne UK team to develop tools that ensure patients are heard,” Abby Bronson, PPMD’s senior vice president for Research Strategy, said in a press release.