An American study carried out in 90 children under three with SMA evaluated the interest of quantifying circulating neurofilaments (NF) to detect the disease and assess the response to different therapies.
Its results show that:
- circulating NF levels are particularly high during the first months period of life in children with SMA and reflect neuronal damage;
- these high concentrations are inversely proportional to the number of copies of SMN2 and the amplitude of the compound muscle action potential (CMAP) of the ulnar nerve;
- initiation of nusinersen therapy is associated with a rapid decrease in circulating NF levels;
- the intervention of treatment as early as possible in the neonatal period ensures the best clinical results (especially for the cohort of children with 2 copies of SMN2);
- gene therapy with onasemnogene abeparvovec (Zolgensma®) would be unexpectedly associated with an increase in circulating NF levels (however the development and motor skills of six out of seven of these children are normal);
- elevated NF related to Zolgensma® treatment could reflect possible toxic effects of uncontrolled over-expression of SMN, causing acute neuronal damage;
- prior treatment with nusinersen appears to protect against the toxicity associated with Zolgensma® infusion.
The evaluation of the circulating NF level shows the interest of treating SMA before developing symptoms.
