Biomarkers of therapeutic efficacy in adolescents and adults with 5q spinal muscular atrophy: a systematic review.

Background: The therapeutic landscape of spinal muscular atrophy (SMA) was dramatically transformed with the introduction of three disease-modifying therapies (DMTs). A systematic review was performed to assess available evidence regarding quantitative therapeutic biomarkers used in SMA patients older than 11 years under treatment with DMTs.

Methods: Latest literature search in MEDLINE, EMBASE, Cochrane databases and gray literature resources was performed in June 2021. Studies reporting only motor function or muscle strength scales or pulmonary function tests were excluded. Primary outcome was the change from baseline score of any serum, cerebrospinal fluid (CSF) or neurophysiologic biomarker examined.

Results: Database and gray literature search yielded a total of 8050 records. We identified 14 records published from 2019 until 2021 examining 18 putative serum, CSF or neurophysiologic biomarkers along with routine CSF parameters in 295 SMA nusinersen-treated type 2-4 patients older than 11 years of age. There is evidence based on real-world observational studies suggesting that serum creatinine, creatine kinase activity levels along with CSF Αβ42, glial fibrillary acidic protein concentration as well as ulnar compound motor action potential amplitude and single motor unit potential amplitude changes may depict therapeutic response in this population.

Conclusion: This systematic review explored for the first-time biomarkers used to monitor therapeutic efficacy in SMA adolescents and adults treated with DMTs. Research in this area is in its early stages, and our systematic review can facilitate selection of quantitative therapeutic biomarkers that may be used as surrogate measures of treatment efficacy in future trials.

Protocol Registration: PROSPERO CRD42021245516.