Effects of exercise and creatine on myosin heavy chain isoform composition in patients with Charcot–Marie–Tooth disease

Abstract

It is not known whether myosin heavy chain (MHC) content changes in response to exercise training or creatine supplementation in subjects with Charcot-Marie-Tooth disease (CMT). Based on previous data, we hypothesized that resistance exercise and creatine would increase the percentage of type I MHC composition in the vastus lateralis muscle and that myosin isoform changes would correlate with improved chair rise-time in CMT subjects. To test this hypothesis, 18 CMT subjects were randomly assigned to either a placebo or creatine group. All subjects performed a 12-week, home-based, moderate-intensity resistance training program. Chair rise-time was measured before and after the training program. Muscle biopsies were obtained from the vastus lateralis before and after the 12-week program. Gel electrophoresis showed a significant decrease (approximately 30%) in MHC type I in CMT subjects given creatine supplementation when compared with placebo. There was a nonsignificant increase in both MHC type IIa (approximately 23%) and MHC type IIx (approximately 7%) in CMT subjects given creatine. Reduced MHC type I content and increased MHC type IIa content correlated with faster chair rise-times (i.e., improved muscle performance). The training-induced change in MHC IIa content was inversely correlated with chair rise-time in CMT subjects given creatine. When the two subject groups were combined, there was a linear, negative relationship between the change in MHC type IIa content and chair rise-time after training and a positive relationship between the training-induced change in MHC type I content and chair rise-time. These data suggest that improved function (chair rise-time) was associated with a lower level of MHC type I and increased MHC type IIa composition. Furthermore, the data are consistent with the hypothesis that creatine supplementation alters MHC composition in CMT patients undergoing resistance training and that MHC changes associated with creatine supplementation can improve muscle function.

In sickness and in health: the widespread application of creatine supplementation

“…In this respect, Cr seems to be effective in relieving symptoms, attenuating depression, and improving the quality of life in patients suffering from posttraumatic stress and fibromyalgia (Amital et al 2006a, b, c). Inborn or acquired diseases characterized by progressive loss of nervous-system cells such as Alzheimer's, Huntington's, Charcot-Marie-Tooth's and Parkinson's disease and amyotrophic lateral sclerosis (ALS) could be also potentially treated by Cr administration (Brewer and Wallimann 2000;Mazzini et al 2001;Tabrizi et al 2003;NET-PDN 2006;Smith et al 2006). These neurodegenerative disorders share common characteristics, including cerebral energy depletion (e.g., low brain Cr content), exacerbated oxidative stress and mitochondrial dysfunction.…”

Isokinetic Testing in Patients with Neuromuscular Diseases

“…The standard isokinetic testing method is not possible in cases of severe muscle weakness, when a patient is not even strong enough to move his/her limb and the lever arm against gravity. 91 Modifying isokinetic protocol to include the maximum speed, at which a muscle can generate torque, may serve as an indicator of the patient's functional potential because daily activities require the ability to develop tension at various velocities. With this method, both the limb and lever are weighed and gravity is compensated actively by the robot motor, which imposes a continuous isokinetic movement on the limb.…”

Mechanisms of exercise limitation and pulmonary rehabilitation for patients with neuromuscular disease

“…99 Although supplemental dietary creatine was not found to improve muscle performance or muscle fiber size above that found with resistance training alone, 99 one morphologic study showed that creatine increased myosin heavy chain type II in HMSN patients undergoing resistance training, and that these changes correlated with improved muscle function as measured by chair rise time. 123 Another study of patients with HMSN showed that the initial strength increase with resistance training could be attributed to improved recruitment of motor units, with a subsequent contribution from muscle hypertrophy. 98 These findings were not replicated in DM.…”

“…Exercise-induced hyperpnea represents flow loading, and training in that regard could include either voluntary isocapnic hyperpnea (which is predominantly a flow-loading type of training) or threshold load training (which has been more frequently studied and may train both the pressure and flow-generating capacity of respiratory muscles). 70 Interventions that may facilitate or enhance the effects of exercise in patients with neuromuscular disease include provision of non-invasive ventilation prior to exercise for patients in whom alveolar hypoventilation may be responsible for the exercise limitation, 69 supplementation with creatine particularly in patients with HMSN 123 or dystrophies, 132 neuromuscular electrical stimulation and partial body weight support in patients with incomplete tetraplegia 118 steroids in DMD 72,133,134 and theophylline in ALS. 102,103 However, the balance of risks and benefits of the latter two options need to be weighed carefully, given the potential complications of long-term systemic steroids, and the narrow therapeutic window of theophylline.…”