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Therapy of collagen VI-related myopathies (Bethlem and Ullrich)

Neurotherapeutics volume 5, pages 613–618 (2008)Cite this article

Summary

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.

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Author information

Affiliations

  1. Laboratory of Myology, Department of Medical Genetics, S. Anna Hospital, University of Ferrara, Via Fossato di Mortara 74, 44100, Ferrara, Italy

    Luciano Merlini

  2. Laboratory of Cell Biology, Istituto Ortopedico Rizzoli, 40136, Bologna, Italy

    Luciano Merlini

  3. Department of Biomedical Sciences, University of Padova, 35121, Padova, Italy

    Paolo Bernardi

Authors
  1. Luciano Merlini
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  2. Paolo Bernardi
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Correspondence to Luciano Merlini.

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Merlini, L., Bernardi, P. Therapy of collagen VI-related myopathies (Bethlem and Ullrich). Neurotherapeutics 5, 613–618 (2008). https://doi.org/10.1016/j.nurt.2008.08.004

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  • DOI: https://doi.org/10.1016/j.nurt.2008.08.004

Key Words

  • Bethlem myopathy
  • Ullrich congenital muscular dystrophy
  • collagen VI
  • outcome measures
  • therapy