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Antisense oligonucleotide (ASO) mediated exon skipping aims to reframe dystrophin transcripts for patients with Duchenne muscular dystrophy (DMD). Currently 4 ASOs have been approved by the Food and Drug Administration targeting exon 45, 51 and 53 based on low level dystrophin restoration. Additional studies to confirm functional effects are ongoing. Furthermore, efforts are ongoing to increase muscle specific delivery of ASOs. Consequently, there are 5 clinical trials ongoing or planned for exon 51 skipping ASOs in Europe. While exon 51 skipping applies to the largest group of patients, DMD expert centers do not have sufficient numbers of patients or capacity to run all these trials in parallel. Even at a national level numbers may be too scarce. At the same time, some families now face the choice between participation in different clinical trials of exon 51 skipping, sometimes in addition to the choice of participating in a micro-dystrophin gene therapy trial. In this opinion paper, we outline the challenges, compare the different exon 51 skipping trials, and outline how different European centers and countries try to cope with running multiple trials in parallel for a small group of eligible patients.

Background: Overweight is a common problem in Duchenne muscular dystrophy (DMD) and is associated with reduced mobility and quality of life. The influence of nutritional intake on (over)weight is unclear. Objective: To investigate weight and energy and macronutrients intake compared to age-specific requirements in DMD patients (4–18 years). Methods: We assessed weight and body mass index (BMI) and the amount of energy (kcal/day) and macronutrients based on self-reported nutrition diaries. Nutritional intake was compared to requirements for 3 age-groups according to the Dutch Healthy Diet Guideline (4–8/9–13/14–18 years) using a student’s t-test, and relations with age and BMI were investigated by means of Pearson’s correlations. Results: Forty-eight patients participated, 22 ambulatory, median age 10.8 years. The majority used corticosteroids (N = 41). Overweight (BMI z-score > 2.07) was present in 19 patients; 6% (4–8 years), 73% (9–13 years) and 47% (14–18 years). Overweight was more common in non-ambulatory (61.6%) than ambulatory patients (13.6%). Patients aged 4–8 received 290 kcal/day more than required (p

Background Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin. DMD is associated with specific learning and behavioural disabilities. In the brain, dystrophin is associated with GABAA receptors and aquaporin-4 in neurons and astrocytes, respectively, but little is known about its function. Objective and methods In this study we aimed to compare the biochemical composition between patients and healthy controls in brain regions that are naturally rich in dystrophin using magnetic resonance spectroscopy. Given previous conflicting results obtained at clinical field strengths, we obtained data using a 7 Tesla system with associated higher signal-to-noise ratio and spectral resolution. Results Results indicated unchanged biochemical composition in all regions investigated, and increased variance in glutamate in the frontal cortex.

Duchenne muscular dystrophy has a severe disease course, though variability exists. Case reports suggest a milder disease course of patients amenable to exon 44 skipping. In this study, we analyzed this and show that age at wheelchair dependence in patients with a dystrophin deletion requiring exon 44 skipping is postponed compared to patients with a deletion skippable by exon 45, 51 and 53 (10.8 versus 9.8 years; P 0.020). This may be explained by more frequent spontaneous exon 44 skipping in patients with a deletion flanking exon 44. This finding has important implications for the development of future Duchenne trials.