November 12, 2017 – Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve motor milestones and in death or the need for mechanical ventilation by 2 years of age.

In a study just published in the New England Journal of Medicine (N Engl J Med 2017; 377:1713-1722), a group of researchers studied functional replacement of the mutated gene encoding survival motor neuron 1 (SMN1) in this disease by means of a single-dose gene replacement therapeutic approach. Thus, in the study, fifteen patients with SMA1 received a single dose of intravenous adeno-associated virus serotype 9 carrying SMN complementary DNA encoding the missing SMN protein. Three of the patients received a low dose (6.7×10¹³ vg per kilogram of body weight), and 12 received a high dose (2.0×10¹⁴ vg per kilogram). The primary outcome was safety. The secondary outcome was the time until death or the need for permanent ventilatory assistance. In exploratory analyses, scores on the CHOP INTEND (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders) scale of motor function (ranging from 0 to 64, with higher scores indicating better function) in the two cohorts and motor milestones in the high-dose cohort with scores in studies of the natural history of the disease (historical cohorts) were compared.