Gain and loss of abilities in type II SMA: A 12-month natural history study.

The advent of clinical trials in spinal muscular atrophy (SMA) has highlighted the need to define patterns of progression using functional scales. It has recently been suggested that the analysis of abilities gained or lost applied to functional scales better reflects meaningful changes. We defined as "gain" a positive change between scores from 0 to either 1 or 2 and as "loss" a negative change from either 2 or 1 to 0. The aim of this study was to describe, over 12 months, which abilities on the Hammersmith Functional Motor Scale Expanded (HFMSE) were more frequently lost or gained in patients with SMA II. The cohort included 614 12-month assessments from 243 patients (age range: 30 months - 63 years; mean 9.94, SD ±7.91). The peak of abilities gained occurred before the age of 5 years while the highest number of lost abilities was found in the group 5-13 years. A correlation between the HFMSE baseline score and the ordinal number of the items was found for both lost (p<0.001) or gained (p<0.001) activities. No correlation was found with SMN2 copy number. These findings will have implications for clinical trial design and for the interpretation of real-world data using new therapeutic approaches.