The therapy, called deramiocel, is the first treatment shown to preserve heart function in Duchenne muscular dystrophy, a rare inherited disease that progressively weakens muscles throughout the body. Heart failure caused by Duchenne commonly leads to early death.

“After more than two decades of hard work, we have demonstrated that deramiocel can slow or even halt not only the loss of upper limb function, but also progression of heart failure in boys and young men with Duchenne,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and senior author of the study. Deramiocel is based on Marbán’s discoveries.

Duchenne muscular dystrophy primarily affects boys because it is caused by a mutation on the X chromosome. Children born with this mutation develop muscle weakness throughout the body, including in the heart. As they grow older, these children have difficulty running, jumping, pedaling a bicycle and doing other activities, and eventually lose the ability to walk. There is no known cure.

Positive Findings

The randomized, double-blind study, called the HOPE-3 trial, compared deramiocel to placebo in 106 participants ages 10 to 22 with advanced disease. Every three months for one year, participants received an IV drip of either deramiocel or a placebo.

Results showed that the therapy slowed weakening of skeletal muscles by 54% and slowed heart dysfunction by 91%. In patients diagnosed with a condition called cardiomyopathy, which impedes the heart’s ability to pump blood, those who received deramiocel showed full preservation or slight improvement of heart function.

“The benefits we observed could mean important improvements in quality of life in people with advanced Duchenne,” said Craig McDonald, MD, distinguished professor of Physical Medicine & Rehabilitation and Pediatrics at UC Davis Health and national principal investigator of HOPE-3. “If young people maintain their upper limb function, it will help preserve their ability to do normal activities, such as feeding themselves. The heart benefits could reduce mortality.”

Decades in the Making

The potential therapy takes a different approach from other therapies that have been studied for Duchenne. Deramiocel is made from cells taken from healthy hearts donated for transplantation but unable to be used as such and that would otherwise be discarded. The work began in 2004, when Marbán first isolated a population of heart progenitor cells called cardiosphere-derived cells. The first clinical studies of cardiosphere-derived cells were performed at Cedars-Sinai, on patients who had survived heart attacks.

Results published in 2012 showed that the cell infusions regenerated heart muscle damaged by heart attack. Ever since, Marbán’s team has been studying the broader therapeutic potential of these cells. The investigators have made several important discoveries, such as that cardiosphere-derived cells secrete packets of RNA molecules that help cells repair the body’s tissues.

In 2011, Catherine Jayasuriya, the mother of a child with Duchenne and a patient advocate, influenced Marbán to turn his focus from studying how cardiosphere-derived cells could repair the heart after a heart attack to studying their potential for Duchenne muscular dystrophy. Jayasuriya’s fundraising provided the seed funding needed for Marbán’s laboratory to launch initial investigations. The biotechnology company Capricor Therapeutics licensed Marbán’s technology and continued the work by running clinical trials studying the safety and efficacy of deramiocel.

“This is the first Phase III trial to show that a cell therapy is effective against a genetic disease, or any type of heart disease,” said Marbán, the Mark S. Siegel Family Foundation Distinguished Professor. 

Investigators plan to continue studying the therapeutic effects of deramiocel, including whether it can be used to treat other diseases with major unmet medical needs.

“These results represent an important advance for cell-based therapy, one driven by relentless scientific pursuit made by Dr. Marbán and team,” said Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs and dean of the Medical Faculty at Cedars-Sinai.

Authors: A complete list of HOPE-3 investigators can be found in the supplementary appendix of the study.

Funding: The HOPE-3 trial was funded by Capricor Therapeutics Inc.

Disclosures: Eduardo Marbán, MD, PhD, is an inventor of patents licensed by Capricor Therapeutics Inc. and holds founder's equity in the company.

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Children with Duchenne typically lose the ability to walk by age 12 and die at a young age, commonly because their heart becomes so weak it can no longer pump blood.

“When we discovered he had Duchenne muscular dystrophy, I really felt like the sky had fallen down. I mean, that was my world,” Jayasuriya said from her home in Newport Beach, California, where she lives with her husband and Dusty.

Duchenne is caused by a mutation on the X chromosome and mostly affects boys. Jayasuriya was determined to find a potential treatment for her son and the approximately 20,000 other children diagnosed with Duchenne around the world each year.

Jayasuriya read a 2011 article in The Economist that described how Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai, was studying how heart stem cells might repair heart damage. A light bulb went off. She requested a meeting with Marbán and the two forged a mission-filled friendship.

In 2013 Jayasuriya raised $150,000 through her organization, Coalition Duchenne, to fund preliminary research. Now 32, Dusty stands to potentially benefit from a cell therapy created from research Marbán has pursued for decades and that his mother helped fund.

The U.S. Food and Drug Administration (FDA) is currently evaluating deramiocel, a cell product that is based on Marbán’s discoveries. If approved, deramiocel would be the first treatment for the heart damage that often kills young people with Duchenne muscular dystrophy.

Children with Duchenne first show problems with walking or moving their arms. Their heart deterioration isn’t obvious until the heart is close to failing.

“The heart is turning into leather inside their chest,” Marbán said. “They're not aware of it until they're much older because the heart has some reserve, but it ends up being heart failure that accounts for most of the deaths from Duchenne.”

Marban is scheduled to discuss his work at a Feb. 25 FDA virtual workshop on cell therapies. The workshop is open to the public and attendees must register here. Marban's presentation is part of a four-scientist panel, “Cell Therapies for Niche Indications: Clinical Insights and Future Directions.”

The Research Begins 

More than 20 years ago, Marbán became interested in using pluripotent stem cells, which can turn into almost any cell in the body, to reprogram heart cells to generate an electrical pulse in people with abnormal heart rhythms—a biological pacemaker. However, given their propensity to migrate and create tumors, such stem cells were not realistically ready for clinical testing. Marbán and colleagues then turned their attention to isolating from the adult human heart a special type of cell capable of repairing damaged tissue.

“The dogma at the time was that once the heart is injured, it's permanent and it doesn't recover,” Marbán said.

In his laboratory, then at Johns Hopkins University, Marbán developed a technique, starting with a small human heart biopsy, to enable heart cells to self-assemble into microscopic clusters called cardiospheres. He and his team further cultured cardiospheres so that they would dissociate into cardiosphere-derived cells or CDCs. The CDCs could be grown in a laboratory and given back to the patient from whose heart they were taken.

When Marbán joined Cedars-Sinai in 2007 as the inaugural director of the Smidt Heart Institute, he began translating his basic work on CDCs into therapeutic studies in patients. Clinical trials showed heart attack patients who received infusions of their own CDCs into their hearts had some regrowth of healthy heart muscle. Curiously, additional research revealed it wasn’t the cells themselves that did the repair.

Ahmed Ibrahim, PhD, MPH, once a PhD student in Marbán’s lab who is now assistant professor of Cardiology at Cedars-Sinai, discovered that CDCs secrete tiny fat droplets called exosomes. These exosomes are full of molecules that support heart repair. This revelation meant that rather than biopsy a patient's heart, grow the cells and inject those cells into the same patient a month later, investigators could use donor hearts to prepare thousands of doses of CDCs that could be available “off the shelf.” Donor hearts are typically donated for transplantation but may be used for research if they cannot be used for a suitable recipient for technical reasons.

Duchenne and Heart Disease

Jayasuriya piqued Marbán’s interest in Duchenne heart disease. He began to study the effects of CDCs in laboratory mice with a genetic defect mirroring that in Duchenne patients. Working with Marbán, Smidt Heart Institute Assistant Professor Russell Rogers, PhD, discovered that CDCs worked well in Duchenne mice when given intravenously, leading to clinical trials in patients with Duchenne. The research verified CDCs could improve heart and muscle function in boys and young men with Duchenne.

The biotechnology company Capricor Therapeutics licensed Marbán’s technology and conducted additional clinical trials that led the company to apply for FDA approval of CDCs, now known as deramiocel, in December 2024. If deramiocel is approved, patients with Duchenne could receive an intravenous infusion of the therapy every three months.

“Our hope is that this therapy will meaningfully slow the progression of the disease and extend patient lives,” Marbán said.

Investigators in Marbán’s laboratory group are continuing to study what makes exosomes from CDCs potent.

“CDCs work by secreting tiny vesicles packed with genetic material,” Rogers said. “We are looking into the possibility that some of this genetic material may be effective when delivered on its own.”

For Dusty, who has lived longer than most people with Duchenne, the potential therapy is a chance to save his heart.   

“This is great news for older people with Duchenne like me,” he said. “This could make a true difference and impact on my life.”

Jayasuriya said the approval would be a game changer. She encourages parents of children with a rare disease like Duchenne not to give up hope.

“There may be something that works for another condition that can actually work for the condition your child has,” she said. “You just never know. There are no rules.”

Read more on the Cedars-Sinai Newsroom: Cell-Derived Therapy May Help Repair Abnormal Heart Rhythm