Novel SDF-1 mRNA Therapy for Prostatic Radiation-Induced Erectile Dysfunction
Abstract
In U.S. military Veterans, prostate cancer is the most common cancer diagnosis. Annually among Veterans, there are approximately 500,000 prostate cancer patients with 15,000 new diagnoses. There are many options to treat prostate cancer, including surgical removal of the prostate, chemotherapy, radiation of the prostate, and hormone therapy. While the treatments are effective at curing prostate cancer with a 5-year 98% survival rate, these same treatments often lead to devastating side effects. Most notably, many prostate cancer survivors suffer from erectile dysfunction, which greatly impacts their overall quality of life and well-being. Erectile dysfunction due to radiation therapy is often the result of radiation-induced damage to healthy nerves and arteries supplying the penis. Unfortunately, when these penile structures are damaged, these patients do not respond to the current available erectile therapies such as Viagra, Cialis, Levitra, or penile injection therapy with vasodilators. All erectile dysfunction treatment options only treat the symptoms and not the underlying disease. A cost-effective therapy that can prevent or reverse the damage to the penile nerves, arteries, and tissues to recover erectile function and provide a long-lasting therapeutic benefit is greatly needed. The goal of this proposal is to develop a long-lasting therapy for radiation-induced erectile dysfunction. Stromal cell derived factor 1 (SDF-1) is produced by various cells in response injury to initiate the repair pathway and recruit circulating stem cells. However, following radiation and hormone therapy, the amount of SDF-1 produced is insufficient to initiate mending. We believe that greatly increasing the production of SDF-1 proteins following radiation and hormone treatment for prostate cancer will repair the damage to the penile nerves, arteries, and tissues and recover erectile function. Using a similar technology to the Pfizer and Moderna COVID-19 vaccines, we propose to increase SDF-1 using a mRNA-based therapy administered by penile injections. To test our hypothesis, we propose to look at the effects of SDF-1 mRNA to increase Schwann cell and neuron survival and growth in pelvic nerves grown in cell culture after castration and radiation therapy. We also propose to examine the ability SDF-1 mRNA therapy to recover erections in animal models of radiation with and without hormone therapy. Finally, we will also administer SDF-1 mRNA therapy to a mouse model with active prostate cancer tumors to confirm that the treatment does not increase cancer progression or impair the effectiveness of radiation therapy. Over the last 30 years, only 20 studies have been published examining the pathological mechanisms leading to radiation-induced erectile dysfunction, and none have assessed the additive impact of castration. Our findings will significantly increase our understanding of radiation-induced erectile dysfunction and bring us closer to finding a treatment. We believe that SDF-1 mRNA-based therapy will improve outcomes in prostate cancer survivors suffering from erectile dysfunction (FY22 PCRP Overarching Challenge) and provide a clear clinical benefit. These studies are in collaboration with the company, Evincis Bio, which is in the process of gathering data for an Investigational New Drug application with the FDA. These studies will help provide further preclinical evidence to support FDA approval to start clinical trials in patients. While this proposal is targeted to radiation-induced erectile dysfunction, SDF-1 mRNA-based therapy has the potential benefit to improve erectile dysfunction in a wide variety of disease states and potentially provide a cure for millions of individuals worldwide.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310227
Entities
People
- Johanna Hannan
Organizations
- East Carolina University
- United States Army