Improving the course of muscular dystrophy?

The suspect of muscular dystrophy may cause anxiety and stress among those affected and their family members. When a definite diagnosis is obtained, the scenario may be very different depending on the genetic cause. This is particularly true in the case of limb-girdle muscular dystrophies, where clinical heterogeneity among and within forms is extreme (1). In the case of Duchenne muscular dystrophy (DMD), such diagnosis corresponds to the certainty of a wheelchair confinement and a shortened life expectancy. But the age and the grade of disease progression has been modified in the course of the last decades, although a causative therapy that restores a functional dystrophin, available for DMD animal models has not yet attained a human application. However, a crucial point to evaluate supportive long life treatments is represented by objective endpoints represented by numbers. The first of these is the true life expectancy of present-day patients with a defined molecular diagnosis of DMD. An important paper (2) published ten years ago measured the mean age of death of DMD boys in Newcastle in the 1960s, which was 14.4 years; after 30 years in 1990s life expectancy was 25.3 years, but only for those receiving ventilatory support. The mean age at which patients lost their ambulation was stable at 9.3 years.

The DMD average lifespan in the course of the years improved all over the world, but both cardiac and respiratory issues must be considered: the presence of cardiomyopathy shortened life expectancy to 16.9 years.

In the current issue of Acta Myologica two papers recalculate this value and confirm the importance of preventing and treating the respiratory failure. In the study of Rall and Grimm (3) survival data were obtained for 94 German DMD patients, born between 1970 and 1980. The median life expectancy was 24 years, but survival with ventilation was 27 years. For those without ventilation it was 19 years. A second larger study (4) reviewed the notes of 835 DMD patients from 1961 to 2006 in Southern Italy. The age of 20 years was reached by 23,3% of patients born in the 1960s, 54% of patients in the 1970s and 59,8% in patients in the 1980s: the 49,2% of DMD patients of this last group were still alive at 25 years of age.

Death occurred on average at 17,7 years in DMD patients without ventilation, but shifted dramatically to 27,9 years using mechanical ventilation. Also in this report the occurrence of cardiomyopathy was very important for life expectancy: the average age of death was 19,6 years, albeit this was improved in the last 15 years.

In this last paper, the Authors propose that DMD should be also considered an adulthood disease, because half of life belongs to adulthood. Nevertheless, the course of children disease remains very severe, with all patients that loss their ambulation before puberty.

But also this may change in the next future. It is today prevalent the use of steroids to treat DMD and some LGMD forms. Steroids slow down muscle disease and improve all objective endpoints of disease. Another crucial point is the medical therapies and the occurrence of cardiomyopathy (5). Among the upcoming possible therapies, the most straightforward are represented by gene replacement strategies (6) Some recent data obtained on hamsters receiving systemic gene therapy reported a worsening of cardiac function, in parallel with skeletal muscle rescue (7-9) This may be not the case with human patients, but the point cannot be ignored considering that these is already a number of antisense oligo trials for DMD boys (10).