D-Methionine for the treatment of Oral Mucositis

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DESCRIPTION (provided by applicant): Mucositis, also called stomatitis, is a debilitating inflammation and ulceration of the lining of the mouth, throat or gastrointestinal tract most commonly associated with radiotherapy or chemotherapy for cancer. In many cases, mucositis can be extremely painful, preventing the patient from eating normally and interfering with swallowing, drinking and speaking. These symptoms are often exasperated by Xerostomia a condition wherein the production of saliva is severely decreased and results in a dry mouth with discomfort, difficulty in speech and swallowing. In the U.S., 20-40 percent of patients undergoing anticancer therapy will develop mucositis to varying degrees and may require de-escalation of the treatment plan thus compromising therapy. In the present proposal we will investigate in Specific Aim 1, the use of D-Methionine as a therapeutic molecule for protecting cells (e.g. epithelial cells) from cytotoxicity induced by chemo- and/or radiation therapy. These in vitro studies will be followed by in vivo experiments in Specific Aims 2 and 3. In vivo studies in Specific Aim 2 will be accomplished using the mouse lip erythema assay to test the hypothesis that D-Methionine, by protecting normal cells from the cytotoxicity of radiation and/or chemo-therapy, prevents the occurrence of lip erythema, a model for human mucositis. Further in vivo studies will be accomplished in Specific Aim 3 using the acute radiation hamster model developed by Dr. Stephen Sonis, a consultant on this proposal. The development of an agent such as D-Methionine that protects normal tissue from the cytotoxic effects of radio- and chemo-therapy without significantly altering the anticancer efficacy of these therapies would significantly enhance the quality of life of patients undergoing cancer therapy. This may also permit the administration of doses of therapy to cancer patients that were previously unachievable due to dose limiting toxicities.