Evaluation of the Telomere Length in Patients with Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by biallelic SMN1 gene loss, leading to motor neuron degeneration and progressive muscle weakness. The SMN protein is also implicated in telomerase biogenesis, suggesting a possible link between SMA and telomere regulation. This study aimed to investigate relative telomere length in pediatric SMA patients and evaluate, for the first time, the potential effects of gene replacement therapy with onasemnogene abeparvovec. Relative telomere length was measured in peripheral blood lymphocytes using quantitative real-time PCR in 58 patients and 58 age- and sex-matched healthy controls. Of the patients, 19 had received gene replacement therapy. SMA patients without this treatment exhibited significantly shorter telomeres compared with controls (p = 0.029), whereas no significant difference was observed between gene-treated patients and controls (p = 0.108). Direct comparison revealed longer telomeres in treated patients than in untreated ones (p = 0.012). These findings indicate that telomere attrition is present in SMA and may be mitigated by gene replacement. While the exact contribution of telomere biology to SMA pathogenesis remains to be clarified, telomere length may represent a biomarker for disease severity and treatment response, as well as a potential therapeutic target in this disorder.