About the Investigator:

Dr. Opatowsky’s research focuses most notably on approaches to alleviate chemotherapy side effects. He received his BSc, MSc, and PhD degrees from Tel Aviv University. After postdoctoral training at Yale Medical School in New Haven, CT, he joined Bar-Ilan University, where he is now a full professor in the Faculty of Life Sciences.

About the Research:

Peripheral neuropathy is a side effect of many chemotherapeutic treatments. Its symptoms include numbness, tingling, and pain in the hands and feet. These symptoms can persist for years, accompanied by impaired function and poor quality of life. Currently, there are no effective treatments for chemotherapy-induced peripheral neuropathy. Development of such a therapy is a crucial medical need.

SARM1 is a protein that regulates metabolism of the small molecule NAD+ in response to injury, and can promote degradation of axons in the neuronal network. Mice that do not synthesize SARM1 are resistant to chemotherapy-induced peripheral neuropathy, without showing any other apparent impediments. Dr. Opatowsky proposes that compounds that inhibit SARM1 could prevent chemotherapy-induced peripheral neuropathy and, in preliminary research, has identified several promising small molecular weight compounds with potential for further therapeutic development. The Opatowsky team proposes to pursue a structure-based drug design cycle that involves determining high-resolution structures of SARM1 in complex with lead compounds, using cryo-EM and x-ray crystallography; and improving lead SARM1 inhibitor compounds by exploring an array of chemically related compounds. Successful conclusion of this research will identify one or more compounds that prevent peripheral neuropathy in cancer patients treated with chemotherapy. This will improve patients’ quality of life, and may also improve prognosis, by enabling increased dosages of chemotherapy agents otherwise limited by side effects.