The aim of this proposal is to evaluate BIO 300 as an effective therapy to prevent and/or mitigate the erectile dysfunction (ED) that is commonly observed following radiotherapy (RT) for prostate cancer. Prostate cancer is the most common cancer among men in the United States. Approximately half of prostate cancer patients will undergo RT as a part of their treatment. Even though 5 year survival rates are high (>99.2%), about half of the men who receive RT will develop ED within 5 years. Radiation-induced ED remains an unmet medical need that severely impacts the sexual health-related quality of life of cancer survivors, especially younger men. Significantly, possible loss of sexual function plays an important role in treatment-related decisions for men with prostate cancer. Humanetics Corporation is developing BIO 300 oral suspension to treat the delayed effects of acute radiation exposure (DEARE), including radiation-induced pneumonitis and fibrosis. BIO 300 has substantial radioprotective effects linked to its strong antioxidant and anti-inflammatory properties, and its effects on cell cycle division. A strong scientific rationale suggests that inflammation and oxidative stress are critica to development of RT-induced ED. Key biological targets of BIO 300 include redox signaling, inflammatory pathways, and oxidative stress pathways. In mice exposed to a lethal dose of thoracic irradiation, BIO 300 was shown to mitigate normal tissue injury and improve survival when treatment was started 24 hours after radiation and continued for just 14 days. These data support the hypothesis that BIO 300 will be equally effective at preventing RT-induced ED.
The aims of this proposal are designed to provide scientific support for this hypothesis.
The first aim will determine the therapeutic efficacy of BIO 300 in a model of RT-induced ED, using objective physiological endpoints and immunostaining for oxidative stress markers.
The second aim will determine the effect of BIO 300 on tumor development in a rodent model of prostate cancer. Toward that goal, the RT-induced tumor growth delay and tumor pathology will be compared for animals treated with BIO 300 vs. those that do not receive BIO 300 therapy. The goal of this aim is to ensure that BIO 300 does not negatively interfere with RT directed at tumors. In actuality, based on a published literature, BIO 300 in combination with RT is expected to enhance tumor growth delay. If successful, these studies will advance the development of BIO 300 as a treatment option for RT-induced ED, and will positively impact cancer survivors living with ED as well as patients diagnosed with prostate cancer in the future.
Erectile dysfunction is an unacceptable toxicity that occurs in more than half of men treated with radiotherapy for prostate cancer. Effective therapies for the prevention and/or mitigation of radiation-induced erectile dysfunction remain an unmet need and if successfully addressed will dramatically improve the psychological, emotional, and social well-being of prostate cancer survivors. This proposal aims to advance the development of a novel pharmaceutical targeting the underlying biological mechanisms responsible for radiation-induced damage to nerve tissue, which, if left untreated, leads to erectile dysfunction.