Spinraza Treatment May Help to Improve Arm Function in Adults
Among adults with spinal muscular atrophy (SMA) being treated with Spinraza (nusinersen), a decrease in levels of the inflammatory protein YKL-40 in the fluid around the brain is associated with improvements in arm and hand function, according to a new study.
“We conclude that YKL-40 in CSF [cerebrospinal fluid] correlated with clinical improvements during treatment and warrants further research,” the scientists wrote.
While stressing that additional study is needed, the team noted that adults with SMA given Spinraza over the course of about two years “showed an overall clinical stabilization as well as improvements in hand grip strength [and] hand motor function.”
The study, “Biochemical and clinical biomarkers in adult SMA 3–4 patients treated with nusinersen for 22 months,” was published in the Annals of Clinical and Translational Neurology. The work was funded in part by Biogen, which markets Spinraza.
Spinraza is the first disease-modifying therapy for SMA to become widely available. It works by boosting levels of the SMN protein that is deficient in SMA and is approved for patients with several types of the disease.
Investigating long-term effects of Spinraza in adults
Now, four scientists in Belgium reported on the outcomes of 16 adults with SMA who were treated with Spinraza for 22 months, or nearly two years.
“Long-term data of sustained therapeutic effect [of Spinraza] are lacking in adults with SMA as most studies are limited to 10–14 months of follow-up,” the researchers wrote. “Additionally, there are currently no biomarkers in serum or cerebrospinal fluid (CSF) that can serve as outcome measures of disease progression and consistently correlate with therapeutic response in adults with SMA.”
Among the patients, 14 had SMA type 3 and two had type 4 disease. The average age at symptom onset was 6.5 years, while the average age upon starting Spinraza treatment was 37.5 years. About two-thirds of the participants (62.5%) were male, and less than half (43.7%) were able to walk.
Over 22 months on Spinraza, measures of hand grip strength among these patients improved significantly — on average, by 54% in the right hand and 50% in the left.
Scores on the revised upper limb module (RULM), a standardized measure of arm function, also significantly improved, as did the medical research council (MRC) sum score and the peak expiratory flow (PEF) rating. The MRC sum score is an assessment of muscle function, and the PEF is a measure of lung function.
“This study demonstrated the prolonged therapeutic effect of [Spinraza] treatment in adults with SMA [types] 3–4, as evidenced by a sustained significant improvement of hand grip strength, hand motor function, MRC sum score, and PEF after 22 months of treatment,” the researchers wrote.
At each Spinraza treatment, samples of blood and cerebral spinal fluid — the liquid around the brain and spinal cord — were collected. The researchers analyzed levels of several biomarkers related to inflammation and neurodegeneration in these samples, and conducted statistical tests looking for associations with clinical outcomes.
The data showed that CSF levels of an inflammatory protein called CHIT1 increased significantly, while levels of a neurodegeneration marker called pNfH decreased significantly. However, neither of these markers showed significant associations with clinical outcomes.
Levels of another inflammatory protein in CSF, YKL-40, tended to decrease with Spinraza treatment, but the change over time was not statistically significant. The researchers noted that YKL-40 levels normally increase with age.
Additional analyses showed that decreases in YKL-40 levels were significantly linked with improvements in arm function as measured by RULM. On average, each 1,887 picogram per milliliter (pg/mL) decrease in YKL-40 predicted a one-point improvement in RULM scores.
“The association between clinical improvements in the RULM score and decreasing levels of YKL-40 suggests that this neuroinflammatory biomarker could play a role in the follow-up of adult SMA patients treated with” Spinraza, the researchers concluded.
Further, they wrote that “it could be hypothesized that the non-significant decrease in YKL-40 over time is an effect of [Spinraza] treatment, as normally concentrations increase significantly during the aging process.”
The team noted that this study is limited by its small sample size and the lack of any control group, stressing a need for further research to validate these findings.