Spinal Muscular Atrophy: Recent Therapeutic Advances Offer Hope

Decoding the Genetic Basis of SMA

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized by degeneration of alpha motor neurons in the spinal cord. The disease is caused by mutations in the SMN1 gene, which encodes the survival motor neuron (SMN) protein. SMN protein is essential for the assembly and maintenance of motor neuron function.

Historically, SMA has been considered a monogenic disease caused by homozygous loss of function mutations in the SMN1 gene.

Recent studies using next-generation sequencing NGS technologies have revealed the presence of modifying SMN2 copy numbers as well as genetic variants in other genes. These variants can account for the clinical heterogeneity of SMA.

Therapeutic Advances in SMA

Recent therapeutic advances have given hope to families and patients by compensating for the deficiency in SMN protein. These therapies include:

Nusinersen (Spinraza)

This is an antisense oligonucleotide that increases SMN2 gene expression, leading to increased production of SMN protein. Nusinersen has been shown to improve motor function in infants and adults with SMA.

Onasemnogene abeparvovec-xioi (Zolgensma)

This is a gene therapy that replaces the defective SMN1 gene with a functional copy. Zolgensma has been shown to be effective in treating infants with SMA.

Risdiplam (Evrysdi)

This is a small molecule that increases SMN2 gene expression, leading to increased production of SMN protein. Risdiplam has been shown to improve motor function in infants, children, and adults with SMA.

Conclusion

Recent therapeutic advances have significantly improved the outlook for patients with SMA. These therapies have the potential to prevent or delay the onset of symptoms, improve motor function, and increase life expectancy.