The severity of motor problems in children at the time of diagnosis with spinal muscular atrophy (SMA) type 2 may help to predict likely disease progression, including the start of scoliosis and required ventilation, according to an Italian observational study.
This is important because a better understanding SMA’s natural history — how it progresses in the absence of treatment — can help in understanding what disease-modifying treatments that now exist for this disease might realistically achieve, its researchers said.
Their study, “Long-term progression in type II spinal muscular atrophy: a retrospective observational study,” was published in the journal Neurology.
Children with type 2 SMA, also called intermediate SMA or chronic infantile SMA, typically show their first symptoms between 7 and 18 months of age. They may sit without support, but most won’t be able to stand or walk independently.
With the approval of Biogen‘s Spinraza (nusinersen) and Novartis’ Zolgensma (onasemnogene abeparvovec-xioi) for different forms of SMA, type 2 SMA patients are getting treatment. In the case of Spinraza, some for more than a year.
In a real-world setting, however, these patients have a much larger range of ages and functional abilities than those enrolled in clinical trials.
For this reason, it is important to understand the disease’s natural long-term progression — especially in children followed since their first years of life — to better assess changes over time and treatment responses, both positive and negative.
Researchers in Italy set out to analyze long-term progression in 73 children with SMA type 2, all being seen at a single center in Rome, using the Hammersmith Functional Motor Scale–Expanded (HFMSE) scale, a diagnostic tool specifically designed to assess motor function in SMA patients.
The HFMSE scale consists of 33 items evaluating a patient’s ability to perform various activities, like rolling over or rising from the floor, with higher HFMSE scores indicating better motor abilities.
The children had a mean age at admission of 6.8 years, and a mean follow-up of 4.6 years, ranging between 6 months and 12.9 years.
Their HFMSE mean total score at baseline (study start) ranged between 0 and 43 (a maximum HFMSE score is 66, meaning all activities are successfully completed).
Results found that overall progression of SMA type 2 is not linear, with patients showing improvements in motor function until around 5 years old, a steep decline between ages 5 and 13 (the start of puberty), and a period of stability or slower decline after that.
Total HFMSE scores decreased by 2.15 points each year in those between 5 and 13, which the team noted clearly indicates a progressive loss of function. Recent surveys also show that families consider the loss of a single point in HFMSE scores to be clinically meaningful.
By age 14, all these children had severe scoliosis with indication for spinal surgery, which likely affected their performance in activities determining later HFMSE scores — which never rose above 10 points after that age.
“Our results confirm that, despite the variability in changes and the possibility of improvement in the first years of life, all patients with type 2 SMA show a clear and progressive decline on the long-term follow-up, regardless of their scores at baseline,” the researchers wrote.
The team then focused on 28 children who were first assessed before age 5 and followed for at least five years. This group showed similar disease progression and HFMSE score decline between ages 5 and 13 years to those across this entire patient group.
Children were then divided in three subgroups according to their HFMSE scores at baseline: patients with scores higher than 22; scores between 11 and 22 (able to roll over completely and show better trunk control); and lower than 11 (unable to roll over completely).
Results showed that those patients with higher motor impairment (the lowest HFMSE scores) at the study’s start had the earliest progression to scoliosis, which was more delayed in the subgroups with better initial motor function (higher HFMSE scores).
Similarly, those with greater motor difficulties at baseline were about two times more likely to require noninvasive ventilation than those with better motor function.
These findings, the researchers said, may help in better interpreting responses to different types of treatments and in designing clinical trials, but more research is needed.