Duchenne Muscular Dystrophy (DMD) is named after Dr Duchenne de Boulogne, who was one of the first to report the disease in detail in the 1860’s. He studied the clinical course of DMD patients for many years and not only described the progressive muscle weakness and the (pseudo) muscle hypertrophy, but he also as early as 1868 mentioned the impairment of intelligence in DMD patients. He noticed an interesting relationship between muscle and brain, which he described as a ‘character obtus … the intellect was dull and speech was difficult’. He brought his findings to the attention of the profession in other countries.
In 1987 Dr Eric Hoffman and Dr Louis Kunkel discovered that DMD was caused by lack of the dystrophin protein, due to mutations in the DMD gene. DMD was one of the first diseases of which the genetic cause and the missing protein was discovered.
Until the early 1990’s only very minimal care was provided to patients and parents were told to ‘Take him home and love him, there is nothing you can do’. Surgery was performed to release contractures of correct the deformity of spine and feet.
In some countries patients had access to non-invasive ventilation as early as the late 1980’s. The use of respiratory support has prolonged the life expectancy of these DMD patients significantly. However, in most countries it took till early 2000 before patients had access and still in many countries around the globe patient do not have access to non-invasive or invasive ventilation.
Since the early 1990’s some specialized centers started to treat ambulant boys with corticosteroids (prednisone and deflazacort) in a trial setting. Ten years later steroids became part of the standards of care for ambulant DMD patients and more and more non-ambulant boys were treated with steroids as well. The use of steroids changed the course of the disease, with amongst others an impact on the age of loss of ambulation (2-5 year delay), age where ventilation is needed and prolonging arm function until the late teens.
Cardiac problems were originally treated only when they became symptomatic, but since 2007 more and more patients were treated preventive with ACE-inhibitors. The preventive use of ACE-inhibitors is now part of the latest standards of care as well.
In 2014 the European Medicines Agency (EMA) granted Conditional Marketing Authorization for Translarna (ataluren) for ambulant patients whose disease is caused by a specific genetic defect (called a ‘nonsense mutation’) in the dystrophin gene and older than 5 years. In 2018 this indication was expanded to younger children (from 2 years on).
In 2016 Exondys51 (eteplirsen), an antisense oligonucleotide (PMO) that modulates splicing to treat DMD patients with a mutation amenable to exon 51 Skipping, received accelerated approval by Food and Drug Administration (FDA).