A team of government researchers led by Dr. Robert Chetlin (Associate Professor and Clinical Director of Sports Medicine at Mercyhurst University, and Research Physiology Contractor in the Division of Safety Research at CDC-NIOSH) collaborated with Dr. Michael Sereda and Dr. Klaus Nave of the Max Planck Institute for Experimental Medicine (MPI) to secure a CMT1A transgenic rat from MPI and establish a breeding colony in the United States. Initial funding for this project was provided by the Hereditary Neuropathy Foundation (HNF).

The research team is examining the effects of a validated, evidence-based mechanical loading protocol called “resistance-type” exercise training on these transgenic CMT1A rats. The animals train on a specialized dynamometer (a machine that measures and applies force, torque, and power) using stretch-shortening contractions (SSCs), which are coordinated sequences of muscle lengthening and shortening that occur in everyday movement for both humans and animals.

The exercise protocol is tightly controlled across all key training variables: volume (repetitions and sets), intensity (effort level), duration (time per session), frequency (sessions per week), and progression (planned increases in training demands over time). At the end of the protocol, the researchers assessed how well the animals had adapted to training using an integrated systems approach that examined four areas:

  1. Functional muscle performance, including strength and total muscular work
  2. Muscle physiology, quality, and the microscopic structure of individual muscle fibers (myofiber histomorphology)
  3. The nerve coating (myelin), the connection between nerve and muscle (neuromuscular junction), and the nerve itself
  4. The genes, proteins, and potential biomarkers that may influence how muscles and nerves function and communicate in response to exercise

The initial findings suggest that SSC-based exercise training may be the preferred mode of resistance training for this model. When the established CMT1A animal model was mechanically loaded using a validated, high-intensity, resistance-type regimen, a dynamic adaptive response resulted. The researchers note this may represent an important direction toward developing a translational approach, with the goal of improving quality of life and independence for people living with CMT.

According to the researchers, this is the first study to combine an established CMT animal model with a validated, adaptive resistance-type exercise training regimen and investigate the effects on PMP22 gene expression in muscle, in any animal or human CMT population.

Key Findings Presented at the 2015 ACSM Annual Meeting

A summary of the most recent findings was presented at the 2015 Annual Meeting of the American College of Sports Medicine (ACSM):

  • A 4.5-week SSC-exercise training protocol elicited an adaptive response in transgenic CMT1A rats.
  • Training-related adaptations included improved relative isometric force production (static strength), maintenance of normalized muscle mass (the ratio of muscle mass to limb length), and a trend toward improved static muscle quality (the ratio of isometric force to normalized muscle mass).
  • Dynamic muscle function also improved, as shown by an increase in positive work and a trend for increased cyclic force during repeated SSCs, along with enhanced dynamic muscle quality.
  • SSC-exercise training reduced expression of the PMP22 gene. PMP22 codes for a protein involved in myelin (the protective coating around nerves); mutations in this gene can cause CMT1A, Dejerine-Sottas Disease, or Hereditary Neuropathy with Liability to Pressure Palsy (HNPP). Reduced PMP22 expression may ultimately improve myelin integrity and function in the trained animals, though the clinical significance of this finding in humans requires further investigation.

Next Steps

The researchers plan to refine the exercise protocol to identify the type, quantity, and frequency of training that provides the greatest functional benefit to transgenic CMT1A rats. Future studies will also examine dietary supplements and small-molecule therapies, both with and without exercise, to determine whether combining exercise with these other interventions produces greater benefit than any single approach alone.

Disclaimer: The information in this article was previously presented at the 2015 Annual Meeting of the American College of Sports Medicine. HNF partially sponsored this research project.