Repair and regeneration

Cell therapy study offers hope for Duchenne muscular dystrophy

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LOS ANGELES—A new study by researchers at the Smidt Heart Institute at Cedars-Sinai Medical Center showed that cardiosphere-derived cells (CDCs) improved cardiac muscle function, walking abilities and survival in a mouse model of Duchenne muscular dystrophy. According to Stem Cell Reports, the CDCs used in the study are the research-grade version of CAP-1002, a cell therapy product from Capricor Therapeutics. Capricor is a clinical-stage biotechnology company focused on the discovery, development and commercialization of biological therapeutics for the treatment of rare disorders.
The Cedars-Sinai researchers tested the effectiveness of CDCs in a mouse model of Duchenne muscular dystrophy, showing that the skeletal and cardiac improvements seen in Capricor’s HOPE-Duchenne study could be directly attributed to treatment with CDCs. According to Dr. Linda Marbán, Capricor president and CEO, “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.”
As A.J. Bergmann, Capricor’s chief financial officer, explained, “A deadly disease with limited treatment options and no cure, Duchenne muscular dystrophy is an X-linked genetic disease that affects boys and young men. It prevents the body from producing dystrophin, a protein required to keep muscle cells intact. The lack of dystrophin causes cellular damage, leading to the progressive weakening of all muscle groups, including the heart, breathing muscles and skeletal muscles like the arms and legs.”
Duchenne muscular dystrophy occurs in one in 3,600 male births and affects all races and ethnic groups. In the United States, 15,000 to 20,000 people have the disease, which affects an estimated 200,000 boys and young men around the world. Most patients die before the age of 30, commonly from heart failure.
CDCs contain progenitor cells derived from donated heart tissue. CAP-1002, Capricor’s lead investigational candidate, comprises allogeneic CDCs.
“The CDCs have been shown to stimulate diverse and lasting changes in cellular behavior by using the natural repair mechanisms of our own natural biological processes,” Bergmann said. “They release exosomes, which serve as the nano-sized messengers for our cells to communicate with one another. This process has been shown to stimulate tissue repair and regeneration with a powerful one-two punch: first reducing inflammation, which then enables new healthy muscle to form.”
Because the CDCs are derived from cardiac tissue, they also have been shown to reduce oxidative stress and scarring that damages cardiac and muscle cells in an animal model of Duchenne muscular dystrophy, according to the study. In addition, they have been shown to increase the integrity of the cells’ mitochondria, which is damaged by Duchenne muscular dystrophy.
Capricor’s therapies are based on research first conducted at John Hopkins University and then at Cedars-Sinai Medical Center. Based on this foundation, the company is working on therapies to treat Duchenne muscular dystrophy and other neuromuscular and orphan diseases where inflammation is a primary cause of the disease process and symptoms.
“While we initially focused on therapies to regenerate heart muscle, we shifted our focus to rare diseases—and specifically to Duchenne muscular dystrophy,” Bergmann reported. “We recognized the regulatory benefits and competitive advantages of pursuing therapies for rare and orphan diseases. The HOPE-Duchenne Trial found 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.”
He added, “We are initiating the HOPE-2 clinical trial to test the safety and efficacy of CAP-1002 in boys and young men with Duchenne muscular dystrophy and reduced upper limb function. Up to 84 boys and young men with Duchenne muscular dystrophy will be enrolled in HOPE-2, a Phase 2, randomized, double-blind, placebo-controlled trial that will test CAP-1002 in participants in the advanced stages of Duchenne muscular dystrophy.”
According to Bergmann, the potential market for CAP-1002 for Duchenne muscular dystrophy is more than $1 billion in the United States alone. The company regards CAP-1002 “as an important tool in the toolbox to treat Duchenne muscular dystrophy,” he said. While gene and other therapies have the potential to restore dystrophin expression and sustain muscle function, there will still be significant inflammation and fibrosis that can offset the restorative effects. CAP-1002 can work synergistically with the emerging disease-modifying therapies to control those additional pathological aspects of Duchenne muscular dystrophy, because CAP-1002’s primary mechanism of action is immunomodulatory, meaning it can help balance inflammation in this chronic inflammatory disease.
“We have secured exclusive worldwide IP rights to CAP-1002,” Bergmann noted. “We have secured FDA designations that would expedite the development and review of a marketing application for CAP-1002 and give Capricor a competitive advantage, if CAP-1002 is approved. These are Orphan Drug Designation, Rare Pediatric Disease Designation and Regenerative Medicine Advanced Therapy Designation.”
Capricor also is in preclinical development for CAP-2003, a cell-free, exosome-based candidate, to treat a variety of inflammatory conditions. The company has received more than $45 million in competitive grants, a loan award and other non-dilutive funding from the California Institute of Regenerative Medicine, the National Institutes of Health and the Department of Defense.

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