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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.

BACKGROUND Duchenne muscular dystrophy (DMD) is characterized by progressive cardiomyopathy. Left ventricular (LV) function may worsen by factors increasing LV afterload such as hypertension and obesity. OBJECTIVE To identify potential modifiable risk factors for progression of cardiomyopathy in Duchenne muscular dystrophy (DMD). METHODS We retrospectively analysed systolic blood pressures (SBP) and body-mass indexes (BMI) from 273 visits of 65 DMD patients aged 4-18 years between 2003 and 2016, divided in 14 age groups. Values were normalized using Z-scores (Z-SBP and Z-BMI). A linear mixed model was used to analyse correlations between Z-SBP and BMI, steroid use, age, ambulatory status and cardiac medication (CM) use. To study the relationship between SBP and BMI and myocardial deformation prior to the onset of clinical cardiomyopathy, LV deformation, defined by global longitudinal strain (GLS), was quantified in a subset of 36 patients

Background Inclusion body myositis is a late onset inflammatory myopathy lacking reliable serum biomarkers for diagnosis and for disease progression. Objective To identify diagnostic and predictive biomarkers, cytokine profiling is used to assess the potential of cytokines to discriminate between cases and controls and to assess whether treatment with methotrexate can influence biomarkers associated with disease progression. Methods The diagnostic and follow-up potential of 48 cytokines was tested using Bioplex-assay and ELISA in sera of healthy individuals, IBM patients and patients with other neuromuscular disorders. Results Ten cytokines (TRAIL, IL-8, MIF, MCP-1, LIF, IP-10, IFN-α2, MIG, bNGF and IL-3) were identified to be good to excellent markers to discern IBM patients from healthy controls. Three cytokines (IP-10, Eotaxin and SDF1A) changed significantly upon methotrexate treatment as compared with the natural clinical course. Muscle strength loss was associated with changes in IL-8 and SDF1A levels. IFN-γ levels were only associated with survival of IBM patients before correction for multiple comparisons. Discussion Cytokine profiling can discriminate IBM patients from healthy controls and other neuromuscular disorders. Immunosuppression with methotrexate affects cytokine levels in IBM. IL-8 and SDF1A could serve as biomarkers for disease progression.

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.

Background: Duchenne muscular dystrophy (DMD) is a progressive muscle disease. No curative therapy is currently available, but in recent decades standards of care have improved. These improvements include the use of corticosteroids and mechanical ventilation. Objective: To present a detailed population based report of the DMD disease course in The Netherlands (1980–2006) and evaluate the effect of changes in care by comparing it with an historical Dutch DMD cohort (1961–1974). Methods: Information about DMD patients was gathered through the Dutch Dystrophinopathy Database using a standardized questionnaire and information from treating physicians. Results: The study population involved 336DMDpatients (70% of the estimated prevalence), of whom 285 were still alive. Mean age at disease milestones was: diagnosis 4.3 years, wheelchair dependence 9.7 years, scoliosis surgery 14 years, cardiomyopathy (fractional shortening