Until a few years ago, there were only symptomatic treatment options for children and adults with spinal muscular atrophy (SMA). This has changed. New evidence reinforces that nusinersen-treated adult 5q-SMA patients can effectively halt natural disease progression and even gain new motor function. In addition, improvements in bulbar and respiratory functions are also evident, which is particularly important for the quality of life of affected patients.
5q-associated spinal muscular atrophy (5q-SMA) results in progressive loss of motoneurons [1,2]. Treatment with nusinersen can slow down increasing muscle weakness and stabilize or even improve motor skills. Clinically significant therapeutic success can also be seen in adult patients with 5q-SMA type 2 or 3, as experts presented at a Biogen symposium at the virtual 93rd DGN Congress using several observational studies [3,4].
Natural course of the disease
In SMA with later onset (SMA types 2 and 3), there is progressive muscle weakness and loss of motor function in all age groups [1,2]. The progressive muscle weakness and concomitant loss of motor function is evident in the natural history of SMA in routine clinical practice, including the following:
- HFMSE*: Decrease of HFMSE score by 0.5 – 1.0 points per year[3].
- RULM**: Decrease of RULM score by 0.41 points per year [5].
- 6-MWD§: decrease in 6-minute walking distance by 20.8 meters (11-19 years) and 9.7 meters (≥20 years) per year, respectively [6].
Recently, the results of a long-term study (1989-2020) of 104 untreated SMA patients were published, reiterating the continuously decreasing muscle strength by dynamometer measurements [2]. Significant increases in muscle strength have been measured in childhood for both SMA type 2 and SMA type 3. However, after maximum muscle strength was reached, it decreased continuously, indicating that SMA types 2 and 3 are degenerative disease patterns with a delayed-onset disease symptomatology. These results justify the use of currently available therapies in adult SMA patients to stop the continuous loss of muscle strength and improve patients’ independence and quality of life [2].
In another study, patients were also found to have progressive bulbar dysfunction and decreased mouth opening in SMA patients, two parameters that have a particularly high impact on quality of life [7]. In essence, patients primarily describe a desire to maintain skills that contribute to being able to live independently. These include, for example, independent eating, independent personal hygiene, or operating a computer keyboard, skills that enable patients to access the labor market and interact with their social environment [8].
Nusinersen in everyday life
The goals of therapy with nusinersen include not only preservation, but also improvement of motor functions in order to preserve the social and financial independence of SMA patients and to enable a positive impact on quality of life. These therapeutic effects of nusinersen were also confirmed in a study of 124 adolescents and adults with 5q-SMA. In this, in addition to stabilization, improvement within several motor function scores was even demonstrated [3].
These findings are reinforced by a 14-month, independent, retrospective cohort study evaluating the efficacy and safety of nusinersen in adults (n = 116; median age 34 years) with genetically confirmed 5q-SMA type 2 or 3 at 18 neurological centers in Italy: on nusinersen, the HFMSE score (median increase) improved by 3 points (p = 0.0014) in sedentary patients and by 2 points (p = 0.00016) in ambulatory patients. In patients with 5q-SMA type 3, a significant improvement in RULM score was observed between study entry and month 14 (+0.5 points [range: -6 to 6]; p = 0.012). Median 6-minute walk distance improved by 20 meters ([range: -101 to 111]; p = 0.016). In the ambulatory patients with 5q-SMA type 3, a significant increase in FVC‡ value was observed after 14 months (+7% [range: +1 to 29]; p = 0.031 [9].
Participants in a recently published study reported overall subjective improvements in terms of greater range of motion in the fingers and hands; louder voice; improved jaw movement and speech, which went against the natural progression of progressive bulbar dysfunction, positively [7].
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