Copaxone may protect heart muscle cells and improve its function after a heart attack
In the late 60s, Weizmann Institute of Science scientists Prof. Michael Sela, Prof. Ruth Arnon and Dr. Deborah Teitelbaum assembled several protein-like molecules called co-polymers, which were designed to cause a disease similar to multiple sclerosis for research purposes. They were surprised to discover that instead of causing a disease, the co-polymers cure it, and one of them became the well-known drug "Copaxone". More than five decades later, the research group of Prof. Eldad Tzhor And Dr. Rachel Sarig from the Department of Molecular Biology of the Cell at the institute, reveals in a new article Published today in the scientific journal Nature Cardiovascular Research Because Copaxone treatment may improve heart function after a heart attack.
A heart attack (myocardial infarction) occurs when the blood supply to a certain area of the heart is blocked. If it is not regenerated quickly, heart muscle cells begin to die. Unlike other tissues in the body, for example skin or skeletal muscles, which can heal from injuries without leaving a scar, heart muscle cells do not have the ability to divide and replace the dead cells with new muscle. Instead, fibroblasts (fiber cells) found in the heart divide rapidly in the damaged area, producing a network of protein fibers that replace the damaged area with scar tissue; This preserves the integrity of the heart, but reduces its contractility and blood flow. Thus, in the long term, the heart attack increases the risk of heart failure - a chronic condition in which the heart is unable to satisfy all the body's needs, initially with effort and later also with rest. Heart failure is a common disease that affects more than 64 million people worldwide.
In the last decade, it becomes clear that the reaction of the immune system following an injury to the heart has a direct connection to its recovery and repair. However, when the inflammatory reaction of the immune system does not disappear and becomes chronic, the damage worsens and heart failure may appear. Since Copaxone is known to change the composition of immune system cells and the proteins they secrete in a way that suppresses inflammation, Dr. Sarig hypothesized that it could be used to examine the question of the effect of the immune system on recovery from a heart attack.
In the new study, under the leadership of Dr. Serig and the research students, the doctor Dr. Gal Avial and Yaakov Elkahal from the laboratory of Prof. Tzhor, the scientists treated mice that had a heart attack with daily injections of Copaxone into the abdominal area. Echocardiograms showed that the treatment improved the heart function of the mice: their heart chambers were able to pump more blood into the large arteries with each beat and thus better supplied vital blood to the body's organs. Also, the scar area was smaller, and large scars covering at least 30% of the left ventricle were observed only in untreated mice. What's more, heart attack victims don't always get to the emergency room right away, and the scientists revealed that Copaxone treatment is effective in mice even when it's started between 24 and 48 hours after the heart attack.
In the next step, the scientists tested the treatment in rats, and this time they started it almost a month after the heart attack, after a chronic condition of heart failure had already developed. The treatment lasted for two months and at the end of it, the amount of blood that the ventricles were able to pump with each beat increased by an average of 30% and an index of the ability of the ventricles to contract improved by almost 60%. One month after the end of the treatment, the blood flow capacity only continued to improve and the contraction index was maintained. Thus, the attempt to answer a basic scientific question - the degree of influence of the immune system on the rehabilitation of the heart - gave rise to a promising direction for a new treatment for a common heart disease.
Surprisingly, the scientists discovered that the drug works not only by affecting the composition of the cells of the immune system in the damaged area of the heart, but also apparently directly protects the heart muscle cells themselves: Copaxone protected the heart muscle cells even in tissue cultures that do not contain cells of the immune system. Later, the treatment also inhibited the division of the fibroblasts that form the scar and increased the formation of new blood vessels.
"The Copaxone treatment does not cause heart muscle cells to divide," explains Dr. Serig. "But it does help the existing cells to survive and contract effectively, causes an increased formation of blood vessels that supply them and delays the formation of the scar." Following the promising findings in the laboratory, the scientists of the institute teamed up with Prof. Ofer Amir and Prof. Rabia Asala from the Hadassah Ein Kerem Hospital, and together with Dr. Aviel and other clinicians, conducted a Phase 2a clinical study to examine the effectiveness of the treatment with subcutaneous injections of Copaxone in heart failure patients. The results of the clinical study have not yet been published, but they will show that there is a rapid improvement in indicators of inflammation and damage to the heart.
"Due to the expiration of the patent on Copaxone, we are facing difficulty in recruiting partners in the industry to continue promoting the research," said Prof. Tzhor. "The process of testing the suitability of an existing drug for a new indication (repurposing) is fast and cheap compared to the development of a new drug, and I hope that a donor or organization will be found to pick up the gauntlet."
Dr. Kafir-Baruch Umansky, Dr. Hanna Boano-Levi, Zachariah Petrover, Yulia Kotlovsky, Dr. Daria Landengoltz, Dr. David Keen, Dr. Lingling Zhang and Shovel Miara from the Department of Molecular Biology also participated in the study. the cell at the institute; Dr. Tali Shalit from the Israeli National Center for Personalized Medicine named after Nancy and Steven Grand at the institute; Dr. Mathias Kramer and Prof. Yifat Marble from the Department of Systemic Immunology at the Institute; Dr. Stav Kozlovski, Prof. Ronan Alon, Dr. Rina Aharoni and Prof. Ruth Arnon from the Department of Immunology and Biological Regeneration at the Institute; Dr. David Mashali and Dr. Uriel Katz from Sheba Medical Center (Tel Hashomer) and Dr. Dean Nachman from Hadassah Ein Kerem Hospital.
More of the topic in Hayadan:
