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/By Alan Gallindoss/
A new Israeli study published in Science Translational Medicine (published by the American Association for the Advancement of Science), demonstrates the mechanism responsible for the destruction of eggs and infertility that occurs with chemotherapy treatments. The study furthermore shows that co-treatment with the immunomodulator drug AS101 during chemotherapy successfully prevented the damage to fertility in mice.
The study was conducted by PhD student Lital Kalich-Philosoph and Dr. Hadassa Roness at the Center for Fertility Preservation at the Sheba Medical Center – Tel Hashomer Hospital in Israel, headed by Prof. Dror Meirow, in collaboration with the Cancer AIDS and Immunology Research Institute at Bar-Ilan University, headed by Prof. Benjamin Sredni.
“AS101 was developed at Bar-Ilan University, ” explains Prof. Sredni. “It is currently in advanced clinical trials for use in cancer patients, and previous studies have shown that it does not affect the efficacy of the chemotherapy treatment, and may even increase the effectiveness of treatment.”
For years, medical research and treatment has been working to find ways to preserve fertility in female cancer patients. Methods such as freezing of eggs or embryos followed by IVF treatments, or freezing of ovarian tissue for transplantation after recovery are routinely practiced but are not suitable for all patients, as well as being invasive and expensive, and carry no guarantee of success. A far better method of preserving fertility in cancer patients would be to prevent the damage and loss of eggs itself that occurs during chemotherapy.
To address this challenge, PhD student Lital Kalich-Philosoph and senior researcher Dr. Hadassa Roness used a mouse model of chemotherapy with Cy treatments to demonstrate that this chemotherapy drug attacks the ovaries by a twofold mechanism. It is toxic to dividing cells and kills actively growing ovarian follicles. At the same time, it also activates dormant follicles, inducing them to grow and proliferate, which makes them susceptible to the effects of the drug as well.
The authors tested the use of an experimental drug called AS101. Mice treated with AS101 in conjunction with Cy fared much better than their counterparts receiving chemotherapy alone. Their primordial ovarian follicles remained dormant, did not start proliferating prematurely, and survived through the entire treatment. Subsequently, the mice that received AS101 along with Cy had normal fertility, whereas the ones treated with Cy alone had a lower rate of pregnancy and fewer total offspring.
Future experiments will be needed to translate this work from mice into human patients and confirm the effectiveness of AS101 for preserving fertility in a clinical setting. The discovery regarding the mechanism behind Cy-induced loss of ovarian reserve is an important breakthrough that will pave the way for additional research into new methods for preserving fertility in cancer patients.
The entire study was carried out in Israel by Israeli researchers and was supported by grants from the Kahn Foundation, Israel Cancer Association, Israel Ministry of Health, Dave and Florence Muskovitz Chair in Cancer Research, and the Jaime Lusinchi Research Institute in Applied Sciences. The participants of these studies were awarded by a number of prestigious prizes.
Additional contributing authors include Dr. Alon Carmely, Dr. Michal Fishel-Bartal, Dr. Hagai Ligumsky, Dr. Shoshana Paglin, Prof. Ido Wolf, and Dr. Hannah Kanety – all of the Sheba Medical Center.
About the Sheba Medical Centre
The Sheba Medical Center at Tel Hashomer is a university-affiliated tertiary referral hospital that serves as Israel’s national medical center in many fields. Adjacent to Tel Aviv, it is the most comprehensive medical center in the Middle East, renowned for its compassionate care and leading-edge medicine. It is also a major medical-scientific research powerhouse that collaborates internationally with the bio-tech and pharmaceutical industries to develop new drugs, treatments and technologies, and a foremost global center for medical education.