Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
Irisin is an exercise-mimetic myokine secreted by skeletal muscle. Compelling evidence in
 animal models and humans showed that Irisin prevents onset of musculoskeletal atrophy and its
 low serum levels are predictive of sarcopenia. The investigators evaluated the levels of
 irisin in patients affected by an hereditary motor and sensory neuropathy, namely
 Charcot-Marie-Tooth disease (CMT), in order to investigate possible key determinants of their
 muscle quality and possibly prevent the progressive distal weakness and muscle atrophy.
Currently, there are no effective treatment approaches for CMT other than treating symptoms
 with medications such as nonsteroidal anti-inflammatory drugs that provide relief of lower
 back or leg pain. Except for the most severe cases in which orthopedic surgery is recommended
 to correct pes cavus and/or spine deformities, rehabilitative management of patients with CMT
 has shown that physical activity can provide a moderate increase in muscle strength and
 musculoskeletal function, improving activities of daily living. Benefits of exercise on the
 musculoskeletal system are widely recognized as primary non-pharmacologic intervention for
 several diseases. The positive outcome of physical activity is achieved not only by the
 mechanical load applied on the musculoskeletal system, but also via biochemical signals, the
 myokines, secreted during contraction that act locally or systemically on several body
 districts. Among these, Irisin is a hormone-peptide synthesized from skeletal muscle
 performing key actions on the whole-body metabolism. In humans, the investigators have
 documented with several studies an existing positive association between circulating levels
 of Irisin and bone mineral density. Very recently, in muscle biopsies of older adult
 subjects, the investigators also observed that the expression of the Irisin precursor, the
 fibronectin type III domain-containing protein 5 (FNDC5), was positively associated with
 Irisin serum levels and osteocalcin mRNA expression in bone biopsies, indicating a strong
 correlation between healthy muscle and bone tissues. In humans, low levels of circulating
 Irisin have been found to be predictive of muscle weakness and atrophy, and Irisin has been
 identified as a sensitive molecular biomarker for sarcopenia in postmenopausal women. In
 addition, women older than 65 years undergoing a 12-week exercise program showed an increase
 in circulating Irisin and an improvement in isokinetic leg strength and grip strength
 compared with control women. Moreover, there was a positive correlation between Irisin levels
 with grip strength and leg strength in the exercise group, suggesting a causal relationship
 between improved muscle strength and increased Irisin concentration. Although numerous
 reports recommend increasing muscle strength in CMT patients to prevent progressive distal
 weakness and muscle atrophy, few studies have investigated the possible key determinants of
 muscle quality in these patients. Therefore, the aim of this study was to evaluate
 circulating Irisin levels in a population of 20 CMT patients as well the association of
 Irisin with biochemical parameters and muscle quality. In addition, the investigators
 compared these data with unpublished data previously obtained in healthy subjects.
Inclusion Criteria:

 -  Definitive diagnosis of Charcot-Marie-Tooth disease

 Exclusion Criteria:

 -  osteoporosis

 -  intestinal malabsorption

 -  chronic inflammatory diseases

 -  chronic renal failure

 -  severe heart failure

 -  neoplastic diseases