Cellular therapy shows promise for Duchenne muscular dystrophy

Possible treatment option for boys and young men with the debilitating disorder


UC Davis Health researchers have announced promising findings from interim results of a clinical trial for Duchenne muscular dystrophy (DMD), a rare genetic disorder that causes muscle loss and physical impairments in youngsters.

Craig McDonald, the national principal investigator, presented early findings from the HOPE-2 clinical trial at the International Congress of the World Muscle Society on Oct. 5 in Copenhagen, Denmark. The researchers tested a cellular therapy aimed at blocking or lessening the usual muscle loss in young people with the disease. It was the first intravenous systemic cell therapy conducted in DMD.

Meaningful results

“This is the first therapeutic to lead to meaningful functional improvements in severe non-ambulatory patients with DMD using the recently validated Performance of Upper Limb (PUL) Measure,” said McDonald, professor and chair of physical medicine and rehabilitation and professor of pediatrics at UC Davis Health. “The consistent benefits across multiple endpoints with this cell-based therapy suggests that this may be an important treatment option for the boys and young men who have this debilitating disorder.”

DMD affects about 1 in 5,000 people – mostly boys – worldwide. It usually becomes apparent in early childhood as weakened skeletal muscles cause delays in milestones such as sitting and walking.

This clinical study assessed the safety and efficacy of stem cells infused intravenously, as well as their impact on skeletal and cardiac muscle function in patients with DMD. Eight participants at the UC Davis site received the stem cells every three months over one year, for a total of four infusions.

Cellular therapy may help

The DMD clinical trial used Capricor’s CAP-1002 progenitor cells. They are a type of adult stem cell that can only undergo differentiation along a specific cell lineage. It means that unlike human embryonic, pluripotent stem cells, they cannot become any cell type. Instead, the primary mechanism of the CAP-1002 therapy is to help balance Duchenne’s serious chronic inflammation problems in patients and thereby maintain or perhaps improve critical cardiac and skeletal muscle function.

Participants received infusions of allogeneic cardiosphere-derived cells made by Capricor. The proprietary treatment consists of a type of progenitor cell that has been shown to exert potent immuno-modulatory activity, reduce muscle inflammation and enhance regeneration. McDonald and his research colleagues are looking at the cells’ therapeutic potential to modify immune system activity to encourage cellular regeneration.

“Over half of the DMD population need power wheelchairs for mobility,” McDonald said. “Their legs and arms lose considerable strength as skeletal muscle tissue is lost. Therapies that address these later stages of the disease can make a tremendous impact on the quality of life for these boys and young men with DMD and lessen the burden of care for their families.”

Collaborations that bring hope

The UC Davis Neuromuscular Research Laboratory runs complex, multidisciplinary trials like HOPE-2 through many collaborations with high-caliber teams of researchers and staff. It partnered with the UC Davis Alpha Clinic for the HOPE-2 study.

The Alpha Clinic is funded by the California Institute for Regenerative Medicine (CIRM), California’s stem cell agency. The clinic serves as a launch pad for testing novel cellular therapies in a wide spectrum of medical conditions, including DMD. The HOPE-2 study was the clinic’s first cellular therapeutic trial. With this great research infrastructure, UC Davis recruited eight of the 20 patients treated nationally.

The UC Davis Neuromuscular research team -- led by clinical research manager Erica Goude and study coordinator Colleen Anthonisen -- were very excited to share the interim results of the study. Given the positive findings, McDonald expects to explore a path for approval from U.S. Food and Drug Administration and to launch a confirmatory multicenter phase III clinical trial.