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Spinal muscular atrophy: Molecular mechanism of pathogenesis, diagnosis, therapeutics, and clinical trials in the Indian context

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Abstract

Spinal muscular atrophy (SMA) is a neuromuscular, rare genetic disorder caused due to loss-of-function mutations in the survival motor neuron-1 (SMN1) gene, leading to deficiency of the SMN protein. The severity of the disease phenotype is inversely proportional to the copy number of another gene, SMN2, that differs from SMN1 by a few nucleotides. The current diagnostic methods for SMA include symptom-based diagnosis, biochemical methods like detection of serum creatine kinase, and molecular detection of disease-causing mutations using polymerase chain reaction (PCR), multiplex ligation-dependent probe amplification (MLPA), and exome or next-generation sequencing (NGS). Along with detection of the disease-causing mutation in the SMN1 gene, it is crucial to identify the copy number of the SMN2 gene, which is a disease modifier. Therapeutic options like gene therapy, antisense therapy, and small molecules are available for SMA, but, the costs are prohibitively high. This review discusses the prevalence, diagnosis, available therapeutic options for SMA, and their clinical trials in the Indian context, and highlights the need for measures to make indigenous diagnostic and therapeutic interventions.

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Notes

  1. Without considering the effect of SMN2 on the phenotype and the 2/0 genotypes, explained in the following sections.

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Acknowledgements

The authors thank Dr. Rakesh K Mishra and Dr. Alok Bhattacharya for their directions and insightful inputs.

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  1. Tata Institute for Genetics and Society, Bengaluru, India

    Ashutosh Aasdev, Sreelekshmi R S, V Rajesh Iyer & Shivranjani C Moharir

  2. WNS Triange, WNS Global, Bengaluru, India

    Ashutosh Aasdev

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  1. Ashutosh Aasdev
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  2. Sreelekshmi R S
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  3. V Rajesh Iyer
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Correspondence to Shivranjani C Moharir.

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Corresponding editor: Alok Bhattacharya

This article is part of the Topical Collection: The Rare Genetic Disease Research Landscape in India.

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Aasdev, A., Sreelekshmi, R.S., Iyer, V.R. et al. Spinal muscular atrophy: Molecular mechanism of pathogenesis, diagnosis, therapeutics, and clinical trials in the Indian context. J Biosci 49, 36 (2024). https://doi.org/10.1007/s12038-023-00412-9

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