The
collagen VI-related
myopathies comprise two major forms,
Bethlem myopathy (BM) and
Ullrich congenital muscular dystrophy (UCMD), which show a variable combination of muscle wasting and weakness, joint
contractures, distal laxity, and respiratory compromise. Specific diagnosis requires molecular genetic testing showing mutation in one of the three genes involved. This review summarizes current treatments, in particular indication for physiotherapy, orthopedic treatment for correction of
foot deformity,
scoliosis, and flexion
contractures of elbows, and treatment of
respiratory failure. The turning point in basic research on
collagen VI
myopathies was the discovery of an unexpected
mitochondrial dysfunction as a pathogenetic mechanism underlying the myopathic syndrome seen in Col6a1 null mice. Treatment of Col6a1(-/-) mice with
cyclosporin A (CsA) rescued the
mitochondrial dysfunction and decreased apoptosis. Similar
mitochondrial defects were revealed in cultures of UCMD patients. The results of an open pilot trial with CsA in five patients with
collagen VI-related
myopathies are summarized and discussed. With the availability of new potential effective treatments, several challenges must be addressed in conducting trials in
orphan diseases and in neuromuscular disorders in particular. Outcome measures are discussed in the context of the expected effect of the cure. Randomized clinical trials often are not feasible for
rare diseases, and sometimes would be ethically inappropriate. The need to develop alternative outcome measures or
biomarkers using platforms such as genomics and proteomics is stressed in this context.