Current Treatment and Management of Dystrophinopathies

Nathalie Goemans, Gunnar Buyse

• Duchenne muscular dystrophy (DMD), the most common and severe type of dystrophinopathy, is a progressive disease affecting primordially skeletal and cardiac muscle. A coordinated multidisciplinary approach is required to address its multisystemic manifestations and secondary problems.• Treatment with glucocorticosteroids (GCS) is accepted as standard of care in ambulant DMD. Daily and intermittent administrations are both in common use with different efficacy and different side effect profile.• There are no established guidelines for age/stage at initiation and treatment duration of GCS. Common practice is initiation of GCS before the child is starting to decline (between age 3 and 6 years) and continuation of monitored treatment after loss of ambulation, aiming at delaying cardiac and respiratory manifestations and preventing the development of scoliosis.• Prevention, monitoring, and treatment of the side effects of long-term chronic GCS use, such as excessive weight gain, hypertension, osteoporosis, impairment of glucose metabolism, delayed puberty, and cataract, should be integrated in the standards of care.• Noninvasive ventilatory support associated with cough assisting techniques has significantly improved the longevity in DMD.• Pharmacologic treatment for cardiac manifestations includes the standard treatments of dilated cardiomyopathy and arrhythmia such as the use of angiotensin converting enzyme (ACE) inhibitors, beta-blockers and diuretics. The lack of robust controlled data hampers clear recommendations about preventive treatment with ACE inhibitors.• DMD is associated with low bone mineral content, which is aggravated by the use of corticosteroids. The use of biphosphonates can be considered in the treatment of painful vertebral fractures. The use of biphosphonates as a preventive treatment should be investigated in randomized controlled studies.• DMD has evolved from a pediatric disease to an adult condition. This underscores the need to prepare adult neurologists for the optimal surveillance and management of patients with a severe chronic disease that have outgrown the pediatric care and that may develop new disease manifestations with improved longevity.