Therapeutic Idea for the Treatment of ALS with RASRx1902
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. ALS is characterized by muscle weakness and is followed by muscle stiffness and paralysis, ultimately leading to loss of vital functions such as speech, swallowing, and breathing. Individuals who develop ALS are usually between 40-70 years of age and it is estimated that at any given point, roughly 20,000 Americans are suffering from ALS. While there are three FDA-approved drugs on the market, they have moderate benefits in treating ALS and there is currently no cure for this disease. The novel therapeutic proposed in this study, RASRx1902, has been tested in several disease models, including Duchenne muscular dystrophy (DMD), systemic lupus erythematosus, and vascular dementia. RASRx1902 has been shown to reduce inflammation and oxidative stress, improve cognitive function, and to have regenerative properties, especially in degenerated muscle. Since all of these factors are known to be involved in ALS, we hypothesize that RASRx1902 will have a beneficial effect in treating this debilitating disease. In this grant, we are proposing to test RASRx1902 in two separate animal models of ALS. These studies will be used to establish: 1. The optimal, most efficacious dose of RASRx1902; 2. The mechanism by which the drug is having an effect in ALS, and 3. The stage of the disease in which it is most effective. In addition, we propose to test RASRx1902 on cells that have been isolated from ALS patients. Usually, cells isolated from ALS patients are not healthy and have a short lifespan. This study will help determine whether RASRx1902 can help improve the health of these cells. Since RASRx1902 targets the pathologic changes observed in ALS, it would be applicable for use in both familial and sporadic cases of the disease. Through the extensive preclinical work that has been conducted on the use of RASRx1902 as a therapeutic for DMD, this molecule has been shown to be safe and efficacious with no toxic side effects. Moreover, its development as an oral formulation makes for an easier transition to the clinic. RASRx1902 is currently being advanced toward an Investigational New Drug application (IND) as a treatment for patients suffering from DMD. As the proof-of-efficacy studies in ALS outlined in this proposal are being carried out, RASRx1902 will be advancing toward a Phase I safety study in healthy volunteers. Preclinical efficacy data acquired by the studies outlined in the proposal would allow for the immediate advancement into a Phase II clinical study in patients suffering from ALS without any further investment. Successful development of RASRx1902 has the potential to improve the treatment, quality of life, and long-term outlook for individuals affected by ALS and reduce overall medical costs related to this fatal disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910471
Entities
People
- Kathleen Rodgers
Organizations
- United States Army
- University of Arizona