Drug protects heart muscle in animal model

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In the late 1960s, three researchers at the Weizmann Institute of Science developed several protein-like molecules called copolymers that they believed would cause a disease similar to multiple sclerosis in laboratory animals. The scientists – Prof. Michael Sela, Prof. Ruth Arnon and Dr. Dvora Teitelbaum – were surprised to discover that the copolymers did not cause the disease, but cured it; one of these molecules became the widely used drug Copaxone. More than half a century later, a new study appears today in Nature Cardiovascular Researcha research team from the Department of Molecular Cell Biology at the Weizmann Institute led by Prof. Eldad Tzahor and Dr. Rachel Sarig, reveal that Copaxone could also facilitate recovery after a heart attack.

Heart attacks occur when the blood supply to part of the heart muscle is interrupted. If that supply is not quickly renewed, 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 (that is, fiber cells) divide rapidly in the damaged area, forming a network of protein fibers that replace the damaged cells with scar tissue. This tissue ensures the heart's integrity but reduces its ability to contract and pump blood. In the long term, therefore, a heart attack increases the risk of heart failure, a chronic condition in which the heart is unable to meet all the body's needs, first during physical exertion and later even at rest. Heart failure affects about 64 million people worldwide.

“Since the patent for Copaxone has expired, we are having a hard time finding partners in the pharmaceutical industry to continue this research.”

Over the past decade, it has been proven that the immune system's response to heart damage is directly linked to heart recovery and rehabilitation. However, if the inflammation triggered by this response does not subside and becomes chronic, the damage worsens even more and can lead to heart failure. Since Copaxone has already been found to alter the composition of immune system cells and the proteins they release, thereby suppressing inflammation, Sarig wondered if it would be possible to use the drug to study how the immune system affects recovery after a heart attack.

In the new study — led by Sarig and two research students from Tzahor's lab, physicians Dr. Gal Aviel and Jacob Elkahal — the researchers treated mice that had suffered heart attacks with a daily injection of Copaxone into the abdomen. Echocardiograms showed that the drug improved the function of the damaged mice's hearts and that their ventricles sent more blood to the major arteries with each heartbeat, which in turn delivered more vital blood to other organs. The area of ​​scarring in the treated mice was relatively small; in addition, large scars covering at least 30 percent of the left ventricle were seen only in mice that were not treated. People who suffer heart attacks don't always go to the emergency room immediately, but the researchers discovered that Copaxone was effective in mice even when treatment began 24 to 48 hours after the heart attack.

The next step in the study tested the treatment in a rat model. This time, however, the researchers began treatment nearly 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 out with each heartbeat had increased by an average of 30 percent, and cardiac contractility—the ability of the heart's chambers to contract—had improved by nearly 60 percent. One month after treatment ended, blood pumping continued to improve, and improvements in cardiac contractility persisted. So while the scientists were trying to answer a fundamental scientific question—how much the immune system affects cardiac rehabilitation—they discovered a promising new way to treat a common heart condition.

To their surprise, the team also discovered that the drug not only affects the composition of immune system cells in the damaged area of ​​the heart, but also appears to directly protect 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 fiber cells that form scar tissue and stimulated the production of new blood vessels.

“Copaxone treatment does not cause the heart muscle cells to divide,” Sarig explains. “It helps existing cells survive and contract effectively, increases production in the blood vessels that supply them, and delays the formation of scar tissue.” Given their promising laboratory results, the Weizmann scientists, along with Aviel and other clinicians, joined forces with Prof. Offer Amir and Prof. Rabea Asleh of the Hadassah Medical Center in Jerusalem to conduct a Phase 2a clinical trial to evaluate the effectiveness of subcutaneous injections of Copaxone in patients with heart failure.

The results of this study have yet to be published, but they are expected to show rapid improvement in markers of inflammation and heart damage. “Because the patent for Copaxone has expired, we are having a hard time finding partners in the pharmaceutical industry to continue this research,” says Tzahor. “Nevertheless, repurposing an existing drug for a new purpose is quick and inexpensive compared to developing a new drug, and I hope a donor or organization will take up the challenge.”

Reference: Aviel G, Elkahal J, Umansky KB, et al. Repurposing glatiramer acetate to treat cardiac ischemia in rodent models. Nat Cardiovascular Res. 2024. doi: 10.1038/s44161-024-00524-x

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