Nusinersen for SMA: expanded access programme.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating motor neuron disorder causing progressive muscle weakness and respiratory insufficiency. We present the initial Australian experiences implementing the expanded access programme (EAP) to enable preapproval access to nusinersen, the first disease-modifying therapy, for SMA type 1. METHODS: An Australian multicentre, open-label EAP for nusinersen enrolled patients with infantile-onset SMA type 1 from November 2016 to September 2017. Standard-of-care medical therapy and treatment with intrathecal nusinersen were provided to all patients. Clinical and diagnostic characteristics, molecular genetics, treatment administered, and functional motor outcomes were assessed. RESULTS: A total of 20 patients with SMA type 1 met the inclusion criteria, of whom 16 consented and received nusinersen treatment. Median time to diagnosis from symptom onset was 5.0 months and was correlated with age of onset (r=0.54, P<0.05). Management shifts included proactive nutritional and pulmonary support in all newly diagnosed patients with increased complexity of decision making. Supplemental nutrition with or without nocturnal non-invasive ventilation was implemented during follow-up in new diagnoses with age of onset <3 months and 2 SMN2 copies. CONCLUSIONS: The nusinersen EAP highlights difficulties in achieving early diagnosis and/or prevention, the evolution of optimal clinical care in a time of uncertain prognostication, resource implications and ethical issues in clinical practice for SMA type 1. These challenges are broadly relevant to the realisation of all novel therapeutics in neurological disorders.

Effect of a multicomponent nutritional supplement on functional outcomes for Duchenne muscular dystrophy: A randomized controlled trial.

BACKGROUND & AIMS: Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular condition causing progressive muscle weakness and premature death. Whilst effective treatments such as gene therapy are developed, families often seek complementary therapies such as nutrition supplements to help their son maintain function; however, there is limited evidence supporting the use of nutritional supplements in DMD. This study aimed to compare the effect of a Standard nutritional supplement with an Enhanced nutritional supplement combining three nutriceuticals on functional outcomes in ambulatory boys with Duchenne muscular dystrophy (DMD). DESIGN: A 50-week double blinded, randomized, controlled crossover trial was conducted in four Australian neuromuscular centres. Primary outcome measures were 6-min walk distance (6MWD) and community ambulation (StepWatch™ Activity Monitoring). Secondary outcome measures included body composition and quality of life. Serum 25-hydroxyvitamin D was measured. RESULTS: Twenty-seven boys completed the intervention. Traditional crossover analysis demonstrated the Enhanced supplement compared to the Standard supplement was associated with a difference of +12 (95% CI: -16, 40) metres in 6MWD, +0.5 (95% CI: -53, 54) inactive minutes per day and -95 (95% CI: -887, 696) steps per day. A mixed effect model indicated a potentially clinically important effect of the Enhanced supplement on the 6MWD of +31 (95% CI: -19, 81) metres. Mean serum 25 hydroxyvitamin D levels at week 50 was 94 (95% CI: 84, 104) nmol/L. There was no observable effect of either supplement regime on body composition or quality of life. CONCLUSIONS: Whilst a positive effect of the Enhanced supplement on functional outcomes was observed, this finding was inconclusive due to the small sample size. The results do not support the use of combined nutritional supplements to improve body composition or quality of life in DMD. A dose of 2000 IU vitamin D was an adequate dose to raise serum 25-hydroxyvitamin D over 50 weeks. CLINICAL TRIAL REGISTRY: Registry #: ACTRN12610000462088, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12610000462088.