Study Findings Offer More Understanding of Natural History of Type III SMA

By assessing longitudinal changes in functional status, researchers are offering a better understanding of the natural history of type III spinal muscular atrophy (SMA), a heterogenous condition that is less represented than other SMA subtypes.

The researchers relied on the Hammersmith Functional Motor Scale Expanded (HFMSE) to examine patterns among a large cohort of patients with type III SMA. HFMSE comprises of 33 items assessing the functional aspects of ambulant patients, with each item being scored on a 3-point scale ranging from 0-2.

The cohort included 182 patients, 136 of which had type IIIA—onset between ages 18 months and 3 years—and 46 of which had type IIIB—onset after the age of 3 years. Patients were followed for a minimum of 6 months and their ages ranged between 30 months and 30 years.

The researchers argue that the observations made throughout the study “will be of use as a reference for the interpretation of the real world data of pediatric and adult type III patients treated with commercially available drugs and, more generally, will help to better understand the natural history of this form of SMA, highlighting the need to prevent the progressive functional decline that, with few exceptions, occurs even in the type IIIB patients.”

HFMSE scores ranged between 4 and the maximum 66 points, with a mean score of 45.37, among the 123 patients who received multiple evaluations for at least 1 year. Just 7 patients reached the maximum of 66 points. These 123 patients accounted for 375 assessments, 51.2% of which had changes between plus or minus 2 points, 32.26% of which had a decrease of more than 2 points, and 16.53% of which had an increase of more than 2 points.

While age, SMA type, and walking status were significantly associated with changes in mean HFMSE score, sex and number of SMN2 copies were not.

“When we analyzed the whole cohort of type III patients there was relative stability with a modest functional improvement until the age of 7, followed by a steeper decline,” explained the researchers. “While both type IIIA and IIIB had a peak around this age, it should be noted that in type IIIB the scores remained relatively stable after the peak until age of 10 years while in IIIA there was in immediate decline.”

The researchers noted that this finding is different from what they’ve reported in type II patients, who reach peak functional achievement at approximately 5 years, which they say confirms previous observations of different trajectories between the progression of the 2 SMA subtypes.

Among the 123 patients, 11 lost their ability to walk without assistance (10 type IIIA and 1 type IIIB) throughout the study period. The mean age the patients experienced this at was 10.21 years, although the mean age was significantly higher for type IIIB patients than type IIIA patients (20.1 and 9.22, respectively).

Reference

Coratti G, Messina S, Lucibello S, et al. Clinical variability in spinal muscular atrophy type III. Ann Neurol. Published online September 14, 2020. doi:10.1002/ana.25900.