Radiation therapy is used alone or in combination with surgery and chemotherapy in the care and management of nearly all adult and approximately 75% of pediatric patients with central nervous system malignancies. Success in controlling a brain cancer by radiation therapy hinges on being able to inactivate the cancer cells while preserving normal tissue function.
This study evaluated retinal endothelial cell response to radiation in the presence of a metalloporphyrin antioxidant, AEOL 10113, using monkey choroid-retina endothelial cells. AEOL 10113 was added to the cells one hour prior to the administration of a single, 10 grey dose of radiation. Statistically significant (P less than 0.05), dose-dependent protection of normal retinal endothelial cells by AEOL 10113 was seen at 24 hours and 48 hours following irradiation. In addition, cell viability was significantly enhanced at 24 hours and 48 hours in non-irradiated endothelial cells cultured with AEOL 10113 at 10ug (P less than 0.05). Laser scanning cytometry showed AEOL 10113 altered cell cycle kinetics and led to significantly (p less than 0.05) increased G1 population 48 hours following irradiation.
The Potential for Metalloporphyrin Antioxidants in Radiotherapy for Cancer
Radiotherapy treatment in cancer has the positive effect of tumor destruction, but also has the negative effect of normal tissue damage. Optimal dosing in radiotherapy balances maximum tumor destruction with minimal toxicity and damage to normal tissue. The "ionizing radiation" used in cancer radiotherapy generates reac tive oxygen species (ROS) and other free radicals. These free radicals cause DNA damage and cell death. Catalytic antioxidants, such as Aeolus' AEOL 10150 and AEOL 10113 have been shown to neutralize free radicals and can reduce radiation-induced normal tissue damage. It is equally important that they also not protect the cancer from radiotherapy. A compound that protected healthy normal cells while not interfering with tumor destruction could provide patients and physicians the ability to either reduce side effects from cancer radiotherapy or to increase the radiotherapy dose, thus enhancing the potential for tumor destruction.
Aeolus' lead compound, a metalloporphyrin antioxidant called AEOL 10150, has been shown to be safe and well-tolerated in both a single and a multi-dose phase 1 studies. In animal models, the compound has shown promise in Amyotrophic Lateral Sclerosis (ALS), protection of healthy cells from radiation therapy, Parkinson's disease, stroke and neurofibromatosis, among other indications. The Company is currently in the process of planning and securing the financial resources to support a phase 2 study to test the efficacy of AEOL 10150 in humans.
About Aeolus Pharmaceuticals
Aeolus is developing a variety of therapeutic agents based on its proprietary small molecule catalytic antioxidants, with AEOL 10150 being the first to enter human clinical evaluation. AEOL 10150 is a patented, small molecule catalytic antioxidant that has shown the ability to scavenge a broad range of reactive oxygen species, or free radicals. As a catalytic antioxidant, AEOL 10150 mimics and thereby amplifies the body's natural enzymatic systems for eliminating these damaging compounds. Because oxygen-derived free radicals are believed to have an important role in the pathogenesis of many diseases, Aeolus' catalytic antioxidants are believed to have a broad range of potential therapeutic uses.
The statements in this press release that are not pur ely statements of historical fact are forward-looking statements. Such statements include, but are not limited to, those relating to Aeolus' product candidates, as well as its proprietary technologies and research programs. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Aeolus' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. Important factors that could cause results to differ include risks associated with uncertainties of progress and timing of clinical trials, scientific research and product development activities, difficulties or delays in development, testing, obtaining regulatory approval, the need to obtain funding for pre-clinical and clinical trials and operations, the scope and validity of intellectual property protection for Aeolus' product candidates, proprietary technologies and their uses, and competition from other biopharmaceutical companies. Certain of these factors and others are more fully described in Aeolus' filings with the Securities and Exchange Commission, including, but not limited to, Aeolus' Quarterly Report on Form 10-Q for the quarter ended December 31, 2006. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof.
Aeolus Pharmaceuticals, Inc.
John L. McManus, President and Chief Executive Officer