Functional and Metabolic Benefits of Inhibiting Myostatin Activation in Conjunction with Neuromuscular Electrical Stimulation
Abstract
The proposed research is applicable to all individuals with spinal cord injury (SCI) but will be most helpful to those individuals who are unable to walk as a result of their SCI, because this group of patients is the least physically active, is at the highest risk of developing cardiometabolic disease, and has the fewest options for engaging in physical activity. Cardiometabolic disease includes many medical problems, from diabetes to problems with cholesterol levels in the blood (low levels of HDL or good cholesterol) to accumulation of body fat and narrowing of the arteries, heart attack, and stroke. The proposed research attempts to reduce cardiometabolic disease risk by combining a treatment proven to improve insulin action, called neuromuscular electrical stimulation (NMES) with a drug that targets myostatin (MSTN). Inhibiting MSTN s actions on the body is expected to improve insulin action and reduce body fat independently of NMES, and the combination of NMES with an inhibitor of MSTN may have greater beneficial effects than either treatment alone, which would be expected to reduce the number of SCI patients who develop diabetes. There are significant clinical implications to the proposed research because of the negative impact of diabetes and cardiovascular disease on quality of life and longevity and the limited ability of persons with SCI to engage in physical activity of sufficient intensity to reduce such risks. Risks of the proposed research are unknown but are expected to be small because the available knowledge regarding inhibition of myostatin action suggest that reduced levels of myostatin are well tolerated in large animals such as dogs, and NMES is FDA-approved and well tolerated. The proposed research is pre-clinical small animal research that is being conducted in parallel with early stage clinical research testing the effects of inhibitors of myostatin for medical problems other than SCI. However, if these studies prove the treatments to be safe and effective with regard to increasing muscle function and/or improving cardiometabolic functions, the time required for clinical translation would be relatively quick. Early clinical trials to test safety and effectiveness of MSTN inhibitory treatments in persons with SCI could be initiated as soon as (1) the proposed animal study is completed and (2) FDA-approval for investigational use of the drugs in the SCI population could be obtained. Clinical deployment would be contingent on outcomes of that research and timelines to FDA approval for clinical use of this family of medications. Regardless of the outcomes, the proposed research will improve the understanding of the functional and cardiometabolic effects of myostatin inhibition to individuals with SCI by conducting a systematic and well-controlled study. This information would be expected to give clear yes or no answers as to whether such treatments should be investigated in the clinic and pursued as therapies to reduced cardiometabolic disorders in those with SCI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810686
Entities
People
- Christopher Cardozo
Organizations
- United States Army