Low cerebrospinal fluid levels of interleukin-8 (IL-8) appear to correlate with better outcomes in patients with spinal muscular atrophy (SMA) undergoing antisense oligonucleotide therapy, according to a recently published study in Neurotherapeutics.

These findings suggest that cerebrospinal fluid IL-8 could be a potential biomarker for treatment response.

Although gene-modulating therapies have proven to be successful in improving symptoms and quality of life in patients with SMA, the mechanisms that cause some patients to respond better to one form of molecular therapy instead of another remain unknown. The authors hypothesize that the utilization of fluid biomarkers could aid in understanding the variability of response to treatment. 

Continue Reading

It is currently impossible to measure survival motor neuron levels in either cerebrospinal fluid or blood. Several other molecules, mainly those implicated in inflammation and neuronal activity, have been proposed as potential biomarkers for treatment response in SMA. However, no studies have analyzed each one systematically. 

Read more about SMA guidelines

The authors aimed to identify proteins that correlated to clinical outcomes by analyzing cerebrospinal fluid samples of 13 children with SMA receiving molecular therapy in the form of nusinersen (Spinraza®) in the hope of detecting potential biomarkers. The main clinical outcome analyzed in the study was changes in baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores.

Notably, children who initiated treatment before 2 years of age had better outcomes than those who began treatment after 11 years of age. Therefore, age grouping has been used as a variable in all statistical analyses.

The assessment of time-dependent relationships of CHOP-INTEND scores and cerebrospinal fluid analyses determined that IL-8 level inversely correlated with CHOP-INTEND scores. This suggests that IL-8 could be used as a potential biomarker to assess response to treatment.

“Baseline CSF IL-8 levels should therefore be prospectively tested—among other fluid and physiologic markers—for stratifying children into better and worse responders when specialty services (e.g., pediatric EMG) are not available, as well as a pharmacodynamic biomarker in treatment trials of other neurodegenerative disorders including ALS,” the authors concluded.


Verma S, Perry K, Razdan R, et al. CSF IL-8 associated with response to gene therapy in a case series of spinal muscular atrophy. Neurotherapeutics. Published online October 26, 2022. doi:10.1007/s13311-022-01305-9