The advent of three approved SMN-upregulating therapeutics for spinal muscular atrophy has dramatically changed the natural history of the disease. There are, however, many uncertainties regarding timing of treatment initiation, response to treatment, and long-term outcomes.  The identification of biomarkers, medical indicators that can inform us as to disease status, treatment response, and/or provide information on likely health outcomes, for SMA is an important step to monitoring disease and understanding treatment to optimize care and outcomes for individuals affected by SMA.

Cure SMA recently convened a working group compromised of 12 SMA professionals with the aim of evaluating potential biomarkers for SMA and outlining further data needed to continue to validate the most promising candidate(s). The working group used a survey technique called the Delphi process to gain consensus and work toward selection of a biomarker for development. The Delphi process consisted of reinerative surveys and phone calls to discuss the questions posed.

Through the Delphi process, the working group decided to focus on neurofilament (NF) as their lead potential biomarker. Neurofilaments are proteins that are released into blood and the cerebrospinal fluid (CSF) when neurons degenerate and die. Higher levels of NF in the CSF in have been observed in infants with SMA (at baseline) than in children without SMA. Furthermore, nusinersen (Spinraza) treatment is associated with decline of NF levels indicating a positive treatment response. In fact, the levels of NF on certain days post treatment initiation seem to be predictive of obtainment of motor milestones like sitting or walking.  While more research and validation is needed, these early results suggest NF may serve as a biomarker of therapeutic response in SMA. Through robust discussion and surveying, the working group identified data elements they would like to collect to continue validation of NF in different patient populations. The working group recently concluded their discussions and a publication regarding these findings is expected in the future, which we hope will guide future research efforts in this area.

For more information on biomarkers and neurofilaments, please see this recently published article in Scientific American.

*This project is sponsored by Biogen and The Miller McNeil Woodruff Foundation