Cellular Therapy Brings Hope to Late-Stage Duchenne Muscular Dystrophy Patients
Early studies of a new drug designed to treat late-stage Duchenne muscular dystrophy show promising, positive results for patients with the greatest unmet need. Led by the neuromuscular program at Cincinnati Children’s, the industry-sponsored trials are now moving into phase 3.
Researchers are testing CAP-1002, a type of cell therapy made from cardiosphere-derived cells (a type of cardiac progenitor cell). In completed phase 1 and phase 2 studies, the treatment shows benefits to heart and skeletal muscles in non-ambulatory male patients with advanced Duchenne muscular dystrophy.
“This is a very precious drug as it is developed from cells cultured from a donor heart,” says Cuixia Tian, MD, principal investigator of the study, director of Cincinnati Children’s Muscular Dystrophy Association clinic and Duchenne Care Center. “Before this, studies focused on younger patients and early-stage treatments. A lot of older boys felt hopeless.”
Duchenne muscular dystrophy (DMD) is the most common form of childhood onset muscular dystrophy. It is a severe, progressive, X-linked disease that was caused by a deficiency of dystrophin protein. This affects the skeletal, respiratory and cardiac muscles. With current standard treatment, individuals with this genetic condition typically lose the ability to walk and develop restrictive lung disease and cardiomyopathy in their teenage years. They face a severely reduced life expectancy.
CAP-1002 is generating a lot of interest among researchers, physicians, patients and families, says Tian, who has been working on DMD research since 2009 when she joined Cincinnati Children’s as a resident.
“This has been a focus for clinical trials in the pediatric neuromuscular field for a long time,” Tian says. “It affects many people.”
Halt Cardiomyopathy Progression-Duchenne Trials
Dubbed HOPE, the Halt Cardiomyopathy Progression-Duchenne trials are sponsored by Capricor Therapeutics.
HOPE 1 was a single center study led by former neuromuscular center cardiologists Michael Taylor, MD, PhD, and cardiology lead John Lynn Jefferies, MD, MPH. Patients received one dose of CAP-1002 delivered by cardiac catheter. Patients were monitored for 12 months.
Study participants showed improvements in their cardiac and skeletal muscles, as reported in an article by Neurology.
CAP-1002's ability to combine anti-inflammatory and regenerative effects showed potential efficacy across the full spectrum of Duchenne muscular dystrophy, regardless of the dystrophin mutation. Researchers noted a slowed disease progression, as well as muscle improvements from baseline, including improved movements of the upper limbs.
Phase 2: Multiple IV Treatments
HOPE 2 was a multi-center phase 2 study that delivered CAP-1002 by peripheral IV treatment. Patients again showed improvements in cardiac and skeletal muscles, as published in The Lancet.
Study participants received CAP-1002 (versus a placebo) four times during a 12-month period. Patients showed stabilization of upper limb function and improved cardiac structure and function.
CAP-1002 appears safe and effective in reducing cardiac and skeletal muscle deterioration in late-stage Duchenne muscular dystrophy patients, without regard to the specific underlying genetic mutation. CAP-1002 uses immunomodulatory, anti-inflammatory and anti-fibrotic actions to slow disease progression.
Tian says this work illustrates the dedication of Cincinnati Children’s research teams to develop new therapies for children with severe disease and improve their lives.
“Their life expectancy is short. Steroids and advanced therapy prolong life but just by a few years, so that is why there is such an urgent need for change,” Tian says. “Especially for the boys already at the advanced stage, they really hope for anything that can help them.”
Bright Future for Therapy that Addresses Duchenne’s Large Disease Burden
Cincinnati Children’s is home to one of the nation’s largest Duchenne muscular dystrophy care centers. The neuromuscular team treats a large population of young adult Duchenne muscular dystrophy patients. By generating research like the CAP-1002 therapy in-house, Cincinnati Children’s places itself at the forefront of genetic and molecular-based disease studies.
With HOPE 2 completed, Tian and her team are now successfully recruiting for the phase 3 studies.
“The interest from our patients and patient families is huge,” Tian says. “When they come to clinic, they’re not just looking for the standard clinical management and optimized care. They always have an interest in the research.”
Consultations and research updates are part of each patient’s clinic visit because that’s what families want. Physicians are expected to participate in and stay updated on neuromuscular research. This feature is why many patients travel to Cincinnati Children’s from out of town for care, Tian says.
“Our families really value that we can hopefully move the field forward and translate our discoveries into the clinical study phase,” Tian says.
CAP-1002’s unique ability to address the large disease burden in non-ambulatory Duchenne muscular dystrophy makes it an excellent candidate for further study.
As phase 3 studies get underway, researchers will look to confirm the therapeutic durability and safety of CAP-1002 for treating skeletal myopathy and cardiomyopathy in Duchenne muscular dystrophy patients.
(Published December 2024)
