PROTECTION FROM RADIATION BY SMALL MOLECULES THAT RAISE NAD

Michael Bonkowski

The Paul F. Glenn Labs, Harvard Medical School, Boston, MA 02115, USA

Abstract

Oral mucositis is a severe debilitating toxicity that causes a breakdown in the mucosa of the mouth and gut, which, in severe cases, limits the treatment and worsens prognosis for the patient. It remains one of the most frequently encountered side effects associated with cancer therapies. Chemo-radiation treatment leads to rapid hyperactivation of a group of DNA-repairing enzymes known as poly-ADP-ribose polymerases (PARPs) that deplete nicotinamide adenine dinucleotide (NAD⁺) and reduce the activity of SIRT1, an anti-inflammatory signaling protein. We will test the hypothesis that the maintenance of NAD⁺ levels by topical treatment with a precursor to NAD⁺, nicotinamide mononucleotide (NMN), will maintain SIRT1 activity and reduce the severity and duration of radiation-induced mucositis. If confirmed, this hypothesis could lead to a new understanding of mucositis and a rapid clinical path to treating this common, debilitating condition.

Keywords: Oral, toxicity, mononucleotide, clinical, activity.