Protection Against Skeletal Muscle Atrophy
Abstract
The present proposed research project falls under the “Solutions to accelerate recovery and restore Warfighter performance in training and operational environments” of the RESTORE Focus Areas. Skeletal muscle atrophy is a response to disuse that occurs during immobilization due to injury, muscle unloading, aging, starvation, and a series of other disease states (cachexia, etc.). Previous studies have demonstrated that patients with muscle atrophy/weakness have a greater burden of illness, require higher resource use, and treatment results in higher healthcare costs. Therefore, it is evident that therapeutic strategies to ameliorate and reduce the recovery period following muscle atrophy would be important to lessen patient suffering and the economic burden associated with this condition. Many diseases and injuries including traumatic skeletal muscle injuries are debilitating and require bed confinement and subsequent lengthy rehabilitation periods due to skeletal muscle atrophy. This is the case for injured combatants and our increasing elderly civilian population. Therefore, treatments that can minimize skeletal muscle atrophy could lead to a faster recovery. Several studies have shown that the heat shock proteins (hsps) are able to protect skeletal muscle against injury. These proteins serve as the cell’s own internal protective mechanism. Our previous studies have shown that administration of radicicol, an hsp-inducing compound, several minutes following frostbite injury is able to preserve muscle morphology and potentially its functional capabilities. This raises the possibility that administration of radicicol or any other hsp-inducing compound may be an important therapeutic mean of minimizing skeletal muscle injury. Our present purpose is to study the potential use of one such hsp inducing compound: alvespimycin (17-DMAG) in order to preserve skeletal muscle from developing atrophy following muscle immobilization. We propose to test the efficiency and frequency of administration of 17-DMAG in order to minimize muscle atrophy during immobilization. In addition, we will examine the persistence of the effect during the recovery period following immobilization. The performance and completion of this research project will permit us to reach a better understanding of how the heat shock proteins protect skeletal muscle from atrophy, as well as to provide the basis for the development of therapeutic compounds and strategies to prevent muscle atrophy. Injuries are common in modern warfare and result in bed confinement for prolonged period of time during the healing process. This results in lengthy rehabilitation due to the development of skeletal muscle atrophy. This represents a serious military concern due to its impact on military readiness. Studies on the topic of skeletal muscle atrophy point to the possibility that an increase in the expression of the heat shock proteins by pharmacological means may result in the attenuation of the negative effects of muscle atrophy and a faster recovery. Therefore, treatments that can block or minimize the development of muscle atrophy are of significant interest. The possibility that administration of 17-DMAG during immobilization or muscle disuse may also ameliorate or block muscle atrophy would represent an important therapeutic mean of minimizing recovery in injured combatants following immobilization.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110132
Entities
People
- Ruben Mestril
Organizations
- Loyola University Chicago
- United States Army