Research Team Discovers How Copaxone Protects Heart Muscle and Improves Function After Heart Attack

In the late 1960s, three researchers at the Weizmann Institute of Science developed several protein-like molecules, called copolymers, that they believed could cause a disease similar to multiple sclerosis in laboratory animals. The scientists, Professor Michael Sela, Professor Ruth Arnon, and Dr. Dvora Teitelbaum, were surprised to discover that instead of causing the disease, the copolymers cured it; one of these molecules became the widely used drug Copaxone.

More than half a century later, in a new study published today in Cardiovascular research on natureA research team from Weizmann’s Department of Molecular Cell Biology, led by Professor Eldad Tzahor and Dr. Rachel Sarig, reveals that Copaxone could also facilitate recovery after a heart attack.

Heart attacks occur when the blood supply to part of the heart muscle is cut off. If this supply is not replenished quickly, heart muscle cells begin to die. Unlike skeletal muscle and other tissues that can recover from injury without scarring, heart muscle cells do not divide and replace dead cells with new muscle.

Instead, the heart’s fibroblasts (i.e., fibrous cells) divide rapidly in the damaged area and create a network of protein fibers that replace the damaged cells with scar tissue. This tissue keeps the heart intact but reduces its ability to contract and pump blood.

In the long term, a heart attack therefore increases the risk of heart failure, a chronic disease in which the heart is unable to meet all the body’s needs, first during physical exertion, then even at rest. Heart failure affects approximately 64 million people worldwide.

Over the past decade, the immune system’s response to heart injury has been shown to be directly involved in cardiac recovery and rehabilitation. But when the inflammation triggered by this response is left untreated and becomes chronic, the damage worsens and can lead to heart failure.

Since it was already established that Copaxone changes the composition of immune system cells and the proteins they release, thereby suppressing inflammation, Sarig wondered whether it might be possible to use the drug to examine how the immune system influences recovery after a heart attack.

In the new study, led by Sarig and two student researchers in Tzahor’s lab, Dr. Gal Aviel and Jacob Elkahal, the researchers treated mice that had suffered a heart attack by injecting them daily with Copaxone into their abdomens. Echocardiograms revealed that the drug improved the function of the mice’s damaged hearts and that their heart chambers sent more blood to the large arteries with each heartbeat, which in turn supplied more vital blood to other organs.

The scar area in the treated mice was relatively small. In addition, large scars covering at least 30% of the left cavity were seen only in untreated mice. People who have a heart attack don’t always go to the emergency room right away, but the researchers found that Copaxone was effective in mice even when treatment began 24 to 48 hours after the heart attack.

The next step in the study was to test the treatment in a rat model, but this time the researchers started the treatment about a month after the heart attack, when the rats were already suffering from chronic heart failure. By the end of the two-month treatment, the percentage of blood pumped with each heartbeat increased by an average of 30 percent, and cardiac contractility (the ability of the ventricles to contract) improved by nearly 60 percent.

One month after treatment ended, blood flow continued to improve and cardiac contractility improved. So, in seeking to answer a fundamental scientific question – how much the immune system affects cardiac rehabilitation – the scientists have discovered a promising new possibility for treating a common heart disease.

To their surprise, the researchers also discovered that the drug works not only by influencing the composition of immune system cells in the damaged area of ​​the heart, but also, it seems, by directly protecting the heart muscle cells themselves: Copaxone protected heart muscle cells in tissue cultures that did not contain immune cells. At a later stage, the treatment also stopped the division of the fibrous cells that form scar tissue and stimulated the production of new blood vessels.

“Copaxone treatment does not cause heart muscle cells to divide,” Sarig says. “It helps existing cells survive and contract efficiently, improves the production of blood vessels that feed them, and delays the formation of scar tissue.”

In light of their promising laboratory results, Weizmann scientists, along with Aviel and other clinicians, teamed up with Prof. Offer Amir and Prof. Rabea Asleh of Hadassah Medical Center in Jerusalem to conduct a Phase 2a clinical trial examining the effectiveness of subcutaneous injections of Copaxone in patients with heart failure.

Results from this trial have not yet been published, but they are expected to show rapid improvement in markers of inflammation and heart damage.

“With the Copaxone patent having expired, we are having difficulty finding partners in the pharmaceutical industry to continue this research,” says Tzahor. “However, repurposing an existing drug for a new use is a quick and inexpensive process compared to developing a new drug, and I hope that a donor or organization will take up the challenge.”