Skeletal and cardiac muscle improvements in MDX mouse

Cedars-Sinai Researchers Say Findings Lay Groundwork for Testing of CAP-1002 in Patients with Duchenne Muscular Dystrophy

Capricor have today announced the online publication in Stem Cell Reports of a new study by researchers at the Smidt Heart Institute at Cedars-Sinai Medical Center, who found that cardiosphere-derived cells (CDCs) improved cardiac muscle function, walking abilities and survival in a mouse model of Duchenne muscular dystrophy. The CDCs used in the study are the research grade version of CAP-1002, Capricor’s cell therapy product.

In the study reported today, the Cedars-Sinai researchers tested the effectiveness of CDCs in a mouse model of Duchenne muscular dystrophy, a progressive and fatal genetic disease. The researchers showed for the first time that the skeletal and cardiac improvements seen in Capricor’s HOPE-Duchenne study could be directly attributed to treatment with CDCs.

“What is most notable about this study is that the researchers further elucidated the mechanism of action of the cells to the exosomes they release,” said Linda Marbán, Ph.D., Capricor president and chief executive officer.

Exosomes are the nano-sized vesicles secreted by the CDCs that serve as cellular messengers carrying out the instructions of the CDCs to treat inflammation and fibrosis. The findings reported today also provide further evidence of the potential of CAP-1002 to stimulate tissue repair and regeneration with a powerful one-two punch: first reducing inflammation, which then enables new healthy muscle to form, as was shown in the mouse model of Duchenne muscular dystrophy.

“Capricor identified the importance of the CDCs to treat Duchenne muscular dystrophy several years ago, and we are delighted to see this extensive body of stellar scientific work published so that others can be aware of its implications as a potential strategy to treat Duchenne muscular dystrophy,” said Dr. Marbán. “This study’s publication helps explain why we are hopeful that our research will continue to show the cells work in people as robustly as they appear to work in mice.”

The HOPE-Duchenne trial found that a single intracoronary dose of CAP-1002 produced significant and sustained improvement in cardiac and skeletal muscle functions in boys and young men in advanced stages of Duchenne muscular dystrophy.

The upcoming HOPE-2 clinical trial will evaluate the safety and efficacy of four intravenous doses of CAP-1002 delivered every three months over a one-year period. It will enroll approximately 84 boys and young men whose ability to walk has been seriously impaired by the loss of muscle function that occurs as Duchenne muscular dystrophy progresses.

“We look forward to initiating HOPE-2 so we can see in a double-blind, randomized, placebo-controlled trial whether the effects seen in the mice and in the first human study are validated,” said Dr. Marbán.

In their published study, the Cedars-Sinai researchers reported that they “had not aspired to restore skeletal muscle function, but merely to offset the pathophysiological consequences of dystrophin deletion in the heart. We now report that CDCs and their secreted exosomes potently improve not only cardiac but also skeletal muscle structure and function…An unanticipated, minor restoration of dystrophin expression was also observed, but this cannot explain all of the observed benefits.”

“CAP-1002 can potentially be very important in the toolbox of therapies which are evolving to treat Duchenne muscular dystrophy,” Dr. Marbán said. “While gene therapy offers tremendous potential in restoring dystrophin expression and sustaining muscle function, there will still be significant inflammation and fibrosis which can offset the restorative effects. We believe that CAP-1002 can work synergistically with the emerging disease modifying therapies to control those pathological aspects of Duchenne muscular dystrophy.”

The researchers also concluded that their findings “further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.”

The CDCs used in the study published in Stem Cell Reports were manufactured at Cedars-Sinai.

More information about the HOPE-2 Trial

About CAP-1002

CAP-1002 consists of allogeneic cardiosphere-derived cells, or CDCs, a unique population of cells that contains cardiac progenitor cells. CAP-1002 has been shown to exert potent immunomodulatory activity and stimulate cellular regeneration. CDCs have been the subject of over 100 peer-reviewed scientific publications and have been administered to approximately 140 human subjects across several clinical trials.