Management and Therapeutic Strategies for Spinal Muscular Atrophy

Abstract

Spinal muscular atrophy is an autosomal recessive neuromuscular disorder characterized by progressive muscle weakness and atrophy. It is one of the most common single-gene disorders with an incidence rate of approximately 1 in 10,000 live births. The clinical manifestations are progressive hypotonia and muscle weakness due to the degeneration of alpha neurons in the anterior horn cells of the spinal cord and motor nuclei in the lower brain stem. Depending on the severity of the symptoms, SMA has five subtypes. Supportive measures can be offered for respiratory, gastrointestinal, and musculoskeletal complications. Carrier testing for all couples is recommended and this can be done by Multiplex Ligation-dependent Probe Amplification (MLPA). Prenatal diagnosis can be offered to carrier couples. Therapies must be given within the newborn period for maximum benefit and before the loss of motor neurons. It is achieved by identifying the SMA babies through Newborn screening. Several new FDA-approved drugs can reduce the progression of symptoms in SMA. However, they cannot offer a definite cure. Clinical follow-up and Neurological assessment demonstrate that SMA children can attain developmental milestones after receiving treatment, which is never normally attained in untreated cases. In utero SMA treatment with Zolgensma would enhance the survival rate and favorable neurological outcomes in the future. Base editing and Gene editing with CRISPR-Cas technologies to target the mutations and restore functional and stable SMN protein levels are the future hopes for a permanent cure of SMA.