Good response to the late treatment with ataluren in a boy with Duchenne muscular dystrophy: could the previous mild course of the disease have affected the outcome?

Abstract

Duchenne muscular dystrophy (DMD) is a severe, progressive X-linked recessive disorder, caused by the absence of the dystrophin protein. A resolutive therapy for DMD is not yet available. The first approved drug for DMD patients with nonsense mutations is ataluren, approved for the treatment of children aged ≥ 2 yrs, that seems effective in slowing the disease progression. An earlier introduction of ataluren seems to give better results. We report the case of a 14-year-old DMD patient with a nonsense mutation in exon 70, still ambulant, who started taking ataluren at 12 years and remained stable for the following two years. The patient was on steroid since the age of 6, with beneficial effects. At two-years follow-up, an optimal disease evolution was observed, associated with a constant decrease of creatine kinase blood levels. Despite the late start of the treatment, ataluren seems to have significantly contributed to the stabilization of the functional status in this patient though it cannot be excluded that the result may have been influenced by the previous favorable course of the disease. However, further studies should be planned in patients with similar age treated with ataluren to better evaluate the treatment's results compared to the natural course of the disease.

Keywords: Duchenne muscular dystrophy; ataluren; nonsense mutation; target therapy; time function tests.

Figure 1.

Time function tests and CK levels during follow-up. A) creatine kinase value (U/L) at different follow-up visits; B) 6 minute walk test results (meters) at different follow-up visits; C) North Star Ambulatory Assessment (score) at different follow-up visits; D) time taken to run/walk 10 meters (seconds) at different follow-up visits; E) time taken to climb 4 stairs (seconds) at different follow-up visits; F) time taken to stand from supine (seconds) at different follow-up visits.

Figure 2.

Muscle MRI. Muscle MRI findings performed at the age of 12 years and 3 months. (A,C,E) Axial turbo spin echo T2 weighted (w), and (B,D,F) short tau inversion recovery (STIR) axial images at the level of the lower leg (A,B), thigh (C,D) and pelvic girdle (E,F) are shown. No significant fat substitution or edema is evident at the level of the leg muscles, in which, by contrast, a mild triceps surae hypertrophy can be detected (A,B). At the level of the thigh (C,D) the adductor magnus, vastus lateralis and intermedius show signs of fat substitution bilaterally, without associated muscle edema. At the level of the pelvic girdle the involvement of the glutei is evident with fat substitution (E) and no corresponding edema (F).