Spinal Müsküler Atrofi ve Gen Tedavisinin Rolü
Synopsis
Spinal Muscular Atrophy (SMA) is an autosomal recessive inherited genetic disease characterized by lower motor neuron degeneration, muscle weakness, and progressive atrophy caused by a decrease in functional SMN protein levels resulting from homozygous deletions or mutations in the SMN1 gene. The disease, which has an incidence of approximately 1:11,000 in live births, is classified into Types 0, 1, 2, 3, and 4 according to the age of symptom onset and the maximum motor function levels achieved. Since the SMN2 gene can produce only a small portion of full-length functional protein, a higher number of SMN2 copies in a patient allows the disease phenotype to be milder. In addition, auxiliary genes such as NAIP, PLS3, CORO1C, and UBA1 also play regulatory roles in pathophysiology and prognosis. Currently, three main FDA-approved therapeutic approaches are available for SMA treatment. Nusinersen (Spinraza) is an antisense oligonucleotide administered via intrathecal injection that regulates SMN2 pre-mRNA splicing to increase full-length protein synthesis. Risdiplam (Evrysdi), taken orally, similarly functions as an SMN2 splicing modifier. Onasemnogene abeparvovec (Zolgensma) is a single-dose intravenous gene replacement therapy that delivers a functional SMN gene to motor neurons via AAV9 viral vectors. Adopting a multidisciplinary approach in cooperation with families is of great importance in disease management and treatment processes.
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