Study finds few cognitive changes after Spinraza treatment
Researchers evaluate the long-term cognitive performance of adults with SMA types 2 or 3
More than a year of treatment with Spinraza (nusinersen) did not result in clinically meaningful changes in cognition for adults with spinal muscular atrophy (SMA), according to a recent study.
While patients did not exhibit widespread cognitive deficits, abnormal performance in certain domains was observed. Scores across most cognitive domains did improve with treatment, but the scientists overall did not consider the gains to be clinically meaningful. The findings do, however, indicate that Spinraza does not negatively affect cognition, the scientists noted.
The study, “Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen,” was published in BMC Neurology.
SMA most often is caused by mutations in the SMN1 gene, leading to a lack of functional SMN protein that’s needed for the health of nerve cells involved in voluntary movement (motor neurons).
As such, progressive muscle weakness and wasting are the hallmark symptoms of SMA. Still, SMA is considered a multi-systemic disease that can be accompanied by a range of nonmotor symptoms.
Historically, research on cognitive function in SMA has taken a back seat to motor function studies. But scientists believe it is of interest given the fact that the SMN protein is found in areas of the brain that are important for cognition.
Available data in children with SMA have indicated that patients have largely normal, or even enhanced cognitive function, according to the authors. In adult patients, the cognitive trajectory is not exactly clear. Moreover, while ample evidence supports the benefits of disease-modifying SMA therapies such as Spinraza on motor function, their effects on cognition remain under-explored.
Study at hospital in Germany
In the study, researchers evaluated the long-term cognitive performance of 23 adults with SMA types 2 (nine people) or 3 (14 people), with a mean age of 38.1, who were seen at a single hospital in Germany and treated with Spinraza.
Motor and cognitive function were evaluated at a clinic visit just before starting treatment (baseline), and again 14 months after initiating Spinraza.
Cognitive function was evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), which was designed for people with amyotrophic lateral sclerosis (ALS).
ECAS assesses three ALS-specific domains — language, verbal function, and executive function ( a set of cognitive skills needed in every day life) — as well as two non-specific domains, namely, memory and visuospatial function. Given certain similarities between the two diseases, the scientists believed the ECAS was an appropriate way of measuring cognition in SMA, for which there is no validated cognitive assessment tool.
Baseline cognitive assessments largely revealed no major differences between patients with SMA type 2 or 3, except for language, for which those with SMA type 3 had lower scores.
While some patients exhibited an abnormal performance across certain ECAS domains, only three people — two with SMA type 2 and one with SMA type 3 — met the clinical cut-off for cognitive impairment based on total ECAS scores.
After 14 months on Spinraza, average scores across all ECAS domains except for visuospatial function improved significantly.
Still, some patients continued to show abnormal performance in some domains. Visuospatial function remained the most severely affected domain after treatment, with 17.4% of patients considered impaired.
Nevertheless, no patient was below the clinical cut-off for cognitive impairment with regard to total ECAS scores.
Gains in functional status
Participants experienced significant improvements in functional status and some indicators of motor function after Spinraza treatment, but motor function was generally not associated with cognitive function at baseline or after treatment.
The researchers noted that while absolute scores on ECAS domains were improved after treatment, this could be due to an increased familiarity with the test, which also is seen in healthy adults.
Overall, the scientists did not consider the observed gains to be clinically meaningful. Still, “[Spinraza] initiation treatment does not have a negative impact on cognition,” the team noted.
Additional studies involving more patients, a treatment-naive control group, and an SMA-specific cognitive assessment may help to strengthen the findings.
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