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# Spinal muscular atrophy (SMA) therapies

Drugs that raise the SMN protein that motor neurons lack in SMA: by changing SMN2 splicing or by adding a working SMN1 gene.

Updated Nov 1, 2026

## What they are

Spinal muscular atrophy is caused by loss of both copies of the SMN1 gene; the nearly identical SMN2 gene makes only a little full-length SMN protein, and its copy number modifies severity. Nusinersen (intrathecal antisense oligonucleotide) and risdiplam (oral small molecule) make SMN2 produce more full-length protein; onasemnogene abeparvovec is a one-time gene therapy that delivers a functional SMN gene.

## Mechanism of action

Most SMN2 transcripts skip exon 7, giving a short, unstable protein. Splicing modifiers shift SMN2 splicing towards exon 7 inclusion, so more functional SMN is made. Gene therapy instead uses an adeno-associated virus vector to deliver a full copy of the human SMN gene into motor neurons. In both cases more SMN protein keeps motor neurons alive.

Target: SMN protein supply: SMN2 pre-mRNA splicing, or SMN1 gene replacement

## Key points

- SMA: both SMN1 copies lost; more SMN2 copies usually means milder, later disease.
- Nusinersen: antisense oligonucleotide given by lumbar puncture; blocks the ISS-N1 silencer in SMN2 intron 7 and promotes exon 7 inclusion.
- Risdiplam: first oral SMA drug, an SMN2 splicing modifier; may harm the fetus, and it raises levels of MATE transporter substrates.
- Onasemnogene abeparvovec: single intravenous AAV gene therapy for children under two years; boxed warning for acute serious liver injury, so corticosteroids and liver tests surround it.

## Drugs in this class

- [**Nusinersen** Antisense oligonucleotide injected by lumbar puncture for spinal muscular atrophy. It makes SMN2 produce more… SMN2 pre-mRNA (intronic splicing silencer ISS-N1 in intron 7)](https://durgical.com/en/pharmacology/nusinersen/)
- [**Risdiplam** First oral drug for spinal muscular atrophy: a small molecule that modifies SMN2 splicing to raise full-length SMN… SMN2 pre-mRNA splicing](https://durgical.com/en/pharmacology/risdiplam/)
- [**Onasemnogene abeparvovec** One-time intravenous gene therapy for spinal muscular atrophy in children under two. An AAV vector delivers a working… Survival motor neuron (SMN) protein, by replacement of the SMN1 gene](https://durgical.com/en/pharmacology/onasemnogene-abeparvovec/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which gene is lost in spinal muscular atrophy, and which gene modifies severity?

SMN1 is lost on both copies; the SMN2 copy number modifies severity.

## What do nusinersen and risdiplam have in common?

Both change SMN2 splicing so that exon 7 is included and more full-length SMN protein is made.

## How does onasemnogene abeparvovec differ from the splicing modifiers?

It is a one-time AAV gene therapy that delivers a functional SMN gene instead of modifying SMN2.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Spinal muscular atrophy: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy/) (MedlinePlus Genetics (U.S. National Library of Medicine), 2018); [Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy](https://pmc.ncbi.nlm.nih.gov/articles/PMC7105407/) (Yonsei Medical Journal, via PubMed Central, 2020); [FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality](https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease) (U.S. Food and Drug Administration, 2019); [FDA Approves Oral Treatment for Spinal Muscular Atrophy](https://www.fda.gov/news-events/press-announcements/fda-approves-oral-treatment-spinal-muscular-atrophy) (U.S. Food and Drug Administration, 2020).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/spinal-muscular-atrophy-therapies/