Home Cellular health Cell therapy improves signs and symptoms of Duchenne muscular dystrophy

Cell therapy improves signs and symptoms of Duchenne muscular dystrophy


Newswise – A clinical trial at UC Davis Health and six other sites has shown a cell therapy holds promise for patients with late-stage Duchenne muscular dystrophy (DMD), a rare genetic disease causing muscle loss and physical impairments for young people.

The therapy appears to be safe and effective in arresting the deterioration of heart and upper extremity functions. It is the first treatment to lead to significant functional improvements in the most severe cases of patients with DMD.

“HOPE-2 is the first clinical trial to test systemic cell therapy in DMD,” said Craig McDonald, the trial’s national principal investigator and senior author of the study. McDonald is Professor and Chair of Physical Medicine and Rehabilitation and Professor of Pediatrics at UC Davis Health. “The trial produced statistically significant and unprecedented stabilization of skeletal muscle deterioration affecting the arms and cardiac deterioration of structure and function in non-ambulatory DMD patients.”

The results of the trial were published today in the Lancet.

Cell therapy for muscle degeneration

In the Phase II clinical trial, researchers used Capricor Therapeutics allogeneic cardiosphere-derived (CDC) CAP-1002 cells obtained from human heart muscle. These cells can reduce muscle inflammation and improve cell regeneration.

“The primary mechanism of CAP-1002 therapy is to help reduce the severe chronic inflammatory problems of the disease, decrease fibrosis and improve muscle regeneration, and thereby maintain or improve critical heart function. and skeletal muscle,” McDonald said.

The trial investigated the long-term efficacy and safety of repeated intravenous infusions of CAP-1002 for the treatment of late-stage DMD. It recruited 20 patients with DMD from seven US centers. The participants were at least 10 years old and had moderate arm and hand weakness. They were randomly assigned to receive either CAP-1002 or a placebo every three months for a year, with a total of four infusions.

Significant improvements in arm, hand and heart function

The team assessed upper limb function using the Performance of Upper Limb Motor Function (PUL) scale for DMD, cardiac function using cardiac magnetic resonance imaging (MRI) ), spirometry measurements of respiratory function and circulating biomarkers.

The researchers assessed the participants’ PUL at their first infusion and after one year. They measured the change in mean/elbow level PUL scores between these two readings. The study found a significant favorable change in participants who received CAP-1002, compared to those who received the placebo. There was significantly less deterioration in upper extremity muscle function in the cell-treated group.

Cardiac MRI also showed that cardiac structure and function appeared to improve in participants who received CAP-1002.

“Here we show the promise of cell therapy in preventing the progression of heart disease in a rare genetic disorder, but there is good reason to believe that such therapy could one day be used for more common forms as well. heart failure,” said co-author Eduardo Marbán, a pioneering cardiology researcher who first discovered that CDCs might be useful in the treatment of DMD. He is Professor Emeritus of the Mark Siegel Family Foundation and Executive Director of the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles.

Moving forward

McDonald and collaborators at other centers in the United States are launching a Phase III clinical trial, HOPE-3. The objective of this study is to confirm the efficacy of CAP-1002 in a larger cohort of patients.

“The FDA has signaled that a larger Phase III study would be the next step toward getting the drug approved. We need to confirm the therapeutic durability and safety of CAP-1002 beyond 12 months for the treatment of heart and skeletal muscle degeneration,” McDonald said.

What is Duchenne Muscular Dystrophy

DMD is a disorder that affects around 1 in 5,000 people, mostly boys. It usually becomes apparent in early childhood, causing progressive weakness and chronic inflammation of skeletal, cardiac and respiratory muscles and delaying milestones such as sitting and walking. Patients with DMD typically lose their ability to walk during their teenage years and develop heart and lung complications as they age.

Treatments for DMD are limited and there is no known cure. Current therapies that target skeletal muscle are not as effective in treating heart muscle weakened by DMD. A therapy that stabilizes or reverses cardiac deterioration, while improving upper extremity function, would be unique in its ability to address the enormous disease burden seen in patients with advanced DMD.

“This cell therapy is innovative in that it meets the critical needs of the most seriously ill patients and stabilizes both the functions of the upper limbs and the heart. Therapies that address the later stages of the disease can have a significant impact on the quality of life of boys and young men with DMD and ease the burden of care for their families,” McDonald said.

Collaborations that made HOPE possible

The team collaborated with researchers and staff at the UC Davis Alpha Stem Cell Clinic, funded by the California Institute for Regenerative Medicine (CIRM). The HOPE-2 study was the clinic’s first cellular therapeutic trial.

“We worked with the Alpha Stem Cell Clinic and benefited from the stellar infrastructure of the Neuromuscular Research Laboratory in the UC Davis Department of Physical Medicine and Rehabilitation and the Center for Clinical and Translational Sciences (CTSC). I think this is a great testament to UC Davis Health’s leadership in stem cell therapeutic trials and translational clinical medicine,” McDonald said.

The team also used the UC Davis Imaging Research Center to obtain cardiac MRI data on trial participants.

The trial (NCT03406780) was sponsored by Capricor Therapeutics.