Aeolus Pharmaceuticals' AEOL 10150 Protects Lungs from Fractionated Radiation; Reduces Angiogenesis and Inflammation

   The primary objective of this study was to determine whether administration of AEOL 10150 reduces the severity of long-term lung injury induced by fractionated radiation. Fisher 344 rats were randomized into five groups: radiation therapy plus AEOL 10150 (2.5 mg/kg BID), AEOL 10150 (2.5mg/kg BID) alone, radiation therapy plus AEOL 10150 (5 mg/kg BID), AEOL 10150 (5 mg/kg BID) alone and radiation therapy alone. Animals received five 8 gray ("Gy") fractions of radiation therapy to the right hemithorax each day for five days. AEOL 10150 was administered 15 minutes before radiation exposure and 8 hours later each of the five days of radiation therapy treatment, followed by subcutaneous injections for 30 days, twice daily. Lung histology at 26 weeks revealed a significant decrease in lung structural damage and collagen deposition in the radiation therapy plus AEOL 10150 (5 mg/kg BID) group, in comparison to radiation therapy alone.

   Immunohistochemistry studies revealed a significant reduction in tissue hypoxia (HIF-1a, CAIX), angiogenic response (VEGF, CD-31), inflammation (ED-1), oxidative stress (8-OHdG, 3-nitrotyrosine) and fibrosis pathway (TGFb1, Smad3, p-Smad2/3), in animals receiving radiation therapy plus AEOL 10150 (5 mg/kg BID). Administration of AEOL 10150 at 5 mg/kg BID during and after RT results in a significant protective effect from long-term radiation therapy-induced lung injury.

   "In addition to its support for the potential use of AEOL 10150 in cancer radiation therapy, this data supports the possible use of AEOL 10150 against radiation-induced tissue damage from radiological or nuclear terrorism and nicely complements ongoing studies showing AEOL 10150 as a potentially protective agent against chemical terrorist agents such as mustard gas," stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. "These studies collectively suggest that AEOL 10150 may be a potent counteract agent against multiple terrorist threats."

   Radiation therapy is used alone or in combination with surgery and chemotherapy in the care and management of nearly all adult and most pediatric patients with lung malignancies. Success in controlling lung cancer by radiation therapy hinges on being able to inactivate the cancer cells while preserving normal tissue function. The National Cancer Institute ("NCI") estimates that there will be approximately 215,000 new cases of lung cancer in the United States and approximately 162,000 deaths. According to the NCI, "results of standard treatment are poor except for the most localized cancers." The American Society for Therapeutic Radiology and Oncology reports that in 2004, nearly one million Americans made 23.4 million visits for radiotherapy treatments for cancer. The total market potential for an effective enhancement to current radiation therapy is estimated to be in excess of $1 billion.

   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 reactive 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, which has been demonstrated in animal studies of both AEOL 10150 and AEOL 10113. A compound that protects 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.

   Keywords: Angiogenesis, Cancer, Fibrosis, Hepatology, Histology, Infectious Disease, Inflammation, Oncology, Pharmaceuticals, Pulmonology, Radiation Therapy, Respiratory Infection, Treatment, Tumor Vascularization, Vascular Endothelial Growth Factor, Aeolus Pharmaceuticals Inc.

   This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2008, Biotech Business Week via NewsRx.com.

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