Stem cells tested to repair dead heart muscle

(U-T San Diego) -- A new stem cell treatment may help heart attack patients do something once thought medically impossible — regenerate dead heart muscle.

Scripps Health in La Jolla is one of three centers testing the therapy from Capricor, a Los Angeles biotech company. The cardiac stem cells are meant to boost the heart's natural ability to perform minor repairs. If it works, scars should shrink and functional heart muscle should grow.

Capricor gets the cells from donor hearts, grows them into the amount needed for treatment, then sends them to doctors taking part in what is called the Allstar trial. Doctors inject the cells into the coronary artery, where they are expected to migrate to the heart and encourage muscle regrowth.

The trial has successfully completed Phase 1, which mainly evaluates safety. On Dec. 17, Capricor said it had received permission to begin Phase 2, which will examine efficacy in about 300 patients who will get the treatment or a placebo. More information can be found at clinicaltrials.gov under the identifier NCT01458405.

The Allstar trial is funded with a $19.7 million "disease team" grant from the California Institute for Regenerative Medicine, or CIRM, the state's stem cell agency.

"This is a highly significant announcement for us at CIRM as it's the first time we've funded a therapy into a Phase 2 clinical trial, Chairman Jonathan Thomas said in a Dec. 23 statement.

About 600,000 Americans die of heart disease annually, making it the leading cause of death, according to the Centers for Disease Control and Prevention in Atlanta. Even those surviving may be left permanently impaired, if the heart is severely damaged. These are the patients Capricor seeks to help.

Mark Athens received Capricor's treatment on Sept. 25, about a month after having a moderate heart attack. The Encinitas resident was the last treated under Phase 1, said Scripps cardiologist Richard Schatz, who performed the procedure. It will take about six months to know whether the treatment worked, Schatz said.

Unlike many trials, Phase 1 was not placebo-controlled, so Athens knows he got the therapy. He appeared cheerful, smiling and bantering with his examining doctor during a Dec. 17 checkup at Scripps Green Hospital.

There's good reason to be optimistic about the treatment, Schatz said, because an earlier Capricor trial with a slightly different approach showed evidence of working.

Positive signs

"All their previous work showed that the scar got smaller and the muscle tissue around it got more robust," Schatz said. "So two things happened: The viable tissue got bigger and the scar got smaller. And that should translate into some sort of clinical benefit down the road."

That study used so-called autologous cells, taken from the treated patient. However, using donor cells is preferred over autologous for practical reasons, Schatz said. Donor cells, called allogeneic, can be banked in advance and used when needed, Schatz said, "just like a blood transfusion." They're also less expensive because of economies of scale.

Schatz said the first study was important as a proof of concept because it dispelled the long-held belief that heart muscle can't be regenerated.

Research by Capricor founder Eduardo Marbán established that the heart contains a kind of stem cell that can turn into new heart tissue. Unlike embryonic stem cells, which can become nearly any cell in the body, these "adult" progenitor cells are limited to differentiating into heart cells.

"No one knew these existed," Schatz said. "Everyone thought the heart was an organ that couldn't repair itself. But it turns out that was wrong, and that there are early progenitor type cells in the heart that no one knew about."

Capricor says that these cells exist in sufficient quantity to repair normal wear and tear on the heart. But they're inadequate to the task of repairing massive heart damage. Adding more of these cells might help, reasoned Marbán, also director of the Cedars-Sinai Heart Institute. Cedars-Sinai is conducting the trial, along with the Minneapolis Heart Institute Foundation and Scripps.

In 2009 Marbán applied for a grant from CIRM to test his approach. He and colleagues explored the concept from the basic biology stage, culminating in the CIRM "disease team" grant that funded the trial of the donor cells.

Cellular reinforcements

The donor cells are unlikely to cause rejection because they are to some extent "immunoprivileged," Schatz said. A simple blood test determines if a potential patient is vulnerable to rejection.

Research published in the Aug. 15 issue of the journal Cell supports Capricor's approach, providing evidence that the cardiac stem cells actually repair damage. The study in rodents found that if cardiac stem cells are

removed, hearts are unable to repair themselves. Moreover, if the removed cells are replaced, hearts regain regenerative ability.

Meanwhile, Athens said he's learned a lot from his own heart attack. Most importantly, he didn't heed the signs when he first experienced chest pain, while drinking coffee on a Monday morning. He ignored the symptoms then, and once again that night.

At 3:30 a.m. Tuesday, Aug. 20, Athens awoke in a cold sweat, clutching his chest in severe pain.

"I attempted to drive myself to the hospital," he said. "I got as far as the fire station."

Athens is now on a restricted activity regimen, while he waits to see whether Capricor's therapy restores his heart.

Other companies are testing their own stem cell therapies for heart disease. San Diego-based Cytori Therapeutics is treating heart failure patients with stem cells taken from the patient's own fat, which it calls adipose-derived stem and regenerative cells. These cells are extracted using Cytori's Celution system.

Cytori said its cells help form new blood vessels and otherwise restore living but damaged tissue to a functional state. More information on what's called the Athena trial is at www.theathenatrial.com.


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