Atrofia Muscolare Spinale: presentazione clinica, quadri radiologici, nuovi trattamenti e biomarcatori

Spinal Muscular Atrophy is an autosomal recessive disorder affecting 1:100,000 live births, in which survival motor neuron (SMN) protein deficiency leads to motor neuron degeneration and progressive muscle atrophy, weakness,and early mortality. Most of SMA patients harbor homozygous SMN1 deletions while SMN2 copy number predicts the clinical subtype (SMA-I, -II, -III-IV). Few (3-5%) SMA patients display small mutations point mutations on the second allele. The behavior of point mutations in SMN1/SMN2 is heterogenous and requires proper validation. In recent years the discovery of effective therapies has marked the history of Spinal Muscular Atrophy(SMA). The only currently approved drug is Nusinersen, which is an antisense oligonucleotide that binds to the SMN2 pre-mRNA downstream of exon 7,leading to the translation of a fully functional SMN protein. The treatment has opened up a new scenario with the creation of a new phenotypic spectrum. We have studied prospectively patients treated with nusinersen, by planning serial evaluations : neurological exam, muscle strength (MRC), motor functional scales, timed tests, muscle MRI, CMAP and MUNE. Monitoring long-term outcome measures will allow us to characterize the new phenotypes of the disease and to define the efficacy spectrum of Nusinersen in patients with different ages and degrees of motor impairment. Neurofilament chains (Nf) are sensitive, liquor-based marker that can identify patients with neurodegenerative diseases, aid in the prediction of their long-term outcomes, and be used for assessing effects of treatment. At present, little is known about serum Nf levels in patients with SMA. To that purpose, we have measured the levels of Nf during the treatment with Nusinersen .