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We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (-7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619.

We describe the experience of parents caring for children with neuromuscular disease (NMD) on home mechanical ventilation (HMV). Data was obtained from semi-structured interviews and analyzed using a phenomenological framework. Fifteen families including 19 parents of children with DMD ( n =3), SMA ( n =5), and other NMD ( n =7) participated. The central theme of these parents' experience was being the "lifeline" for their child's life and quality of life. The families' lives changed significantly with the decision to place their child on HMV; over time, these changes became part of their new "normal". Despite becoming expert caregivers, the parents experienced a recurrent sense of loss and uncertainty. Those who perceived insufficient support felt the weight of responsibility as sole care providers for their child with NMD. Beyond recognizing the parents as experts, more support by health care professionals, their extended family, and their community are needed to enable parents to fulfill their vital role.

Duchenne Muscular Dystrophy (DMD) is now an adult disease. Successful adults with DMD need to acquire the necessary educational, vocational and psychosocial skills and transition to adult services including health care. Several obstacles to successful transition have been described. These include a lack of transition programs which focus, on education, vocation, relationships and independence. Further, since this was previously a paediatric disease there are few professionals who are comfortable and knowledgeable about the needs of adults with DMD. The objective of this study was to describe the current practice for Transition in Canada. A questionnaire was developed and sent to members of the Canadian Pediatric Neuromuscular Group which includes 18 centers across Canada. Local programs and services for Transition were described. These included the process of preparing adolescents for adulthood, independence skills to be developed prior to transition, discussing legal documents and the process to transition them from paediatric to adult services. Transition practices across Canada varied widely. There are varying transition approaches and comprehensiveness of programs to prepare adolescents to transition to adult services. The approaches need to be tailored to the individual and need to be developmentally appropriate. The adolescent’s motivation and parent readiness affect the success of information sharing and skills training. There continues to be gaps in the timing and availability of services. We need: research to determine what strategies will work with the majority of adolescents and secure adult resources to facilitate their successful transition into their community and reduce the burden of care that invariably accompanies unsuccessful transition.

Congenital muscular dystrophy secondary to variants in the lamin A/C gene (LMNA-CMD) typically present with hypotonia at birth, poor axial and truncal control, progressive joint contractures (sparing the elbow) and spinal rigidity. Patients with the congenital onset form can be divided into 2 severity classes: early severe (no ambulation and need for ventilator support in early childhood) and a later onset (brief period of ambulation, ventilator support in late childhood to early teenage years). We present 3 children with LMNA-CMD; all developed cardiac sequelae, diarrhea, and generalized edema. First manifestations of cardiac disease was asymptomatic atrial dysrhythmia. Cardiac disease progressed in early teenage years, in spite of appropriate rate control medication with the onset of cardiomyopathy and ventricular tachycardia. Automatic implantable cardiac defibrillators were recommended, though optimal timing of placement remains unclear. Gastro-intestinal (GI) symptoms, including diarrhea and abdominal distention may herald the onset of worsening cardiac function prior to the onset of overt cardiomyopathy. The etiology of gastrointestinal symptoms is likely multifactorial, including protein loss and gut hypo-perfusion. GI symptoms may respond to steroid therapy and a high protein diet, in spite of a negative work up for protein losing enteropathy.