What is spinal muscular atrophy?

Spinal muscular atrophy is a hereditary neurodegenerative disease — caused by deletion of the SMN1 gene, resulting in insufficient SMN protein and progressive degeneration of spinal cord motor neurons. Without treatment, the most severe form (SMA type 1) was the most common genetic cause of infant death, with children never achieving independent sitting and dying from respiratory failure by age 2. Three approved treatments (nusinersen, risdiplam, zolgensma) have transformed SMA from a fatal disease to a manageable — and in some cases near-normal — condition.

What are the SMA types?

SMA is classified by age of onset and motor milestones achieved: Type 1 (Werdnig-Hoffmann, approximately 60% of SMA): onset before 6 months; never sits independently; respiratory failure by age 2 without treatment; most common and severe. Type 2 (Dubowitz, approximately 27%): onset 6-18 months; sits but never walks independently; respiratory support often needed. Type 3 (Kugelberg-Welander, approximately 12%): onset after 18 months; walks independently at some point; variable later course. Type 4 (approximately 1%): adult onset; mild weakness; normal lifespan.

Why is newborn screening so important?

The window for maximum treatment benefit is extremely narrow — particularly for SMA type 1, where every day without treatment means irreversible motor neuron loss. Pre-symptomatic treatment (before any muscle weakness develops) with nusinersen, risdiplam or zolgensma achieves outcomes indistinguishable from unaffected children in many cases — sitting, standing, walking. Symptomatic infants still benefit substantially from treatment (dramatically extended survival, improved function) but rarely achieve the same outcomes as pre-symptomatically treated infants. This makes SMA one of the strongest arguments for expanding newborn screening programmes.

How does zolgensma work?

Onasemnogene abeparvovec (Zolgensma) is an AAV9 gene therapy — a one-time IV infusion delivering a functional copy of the SMN1 gene packaged in an adeno-associated virus (AAV9) that efficiently crosses the blood-brain barrier and infects spinal cord motor neurons. Once inside motor neurons, the functional SMN1 gene produces normal SMN protein permanently (in theory — long-term durability data are maturing). Approved for SMA patients under age 2 (motor neurons are more amenable to rescue in the youngest infants). The $2.125M price (at FDA approval) made it the most expensive single-dose drug in history.

Why does SMA treatment access matter so much?

SMA type 1 has a critical window — the younger the child is when treatment starts, the better the outcome. In high-income countries, newborn screening identifies SMA within days; treatment starts within weeks. In LMICs, where no SMA newborn screening exists, children typically present clinically (with established weakness) — much later. Even then, the $2.125M zolgensma, $750K+ annual nusinersen, or $340K annual risdiplam are far beyond healthcare budgets. Most SMA children in LMICs receive supportive care only and die within 2 years. This is one of the starkest treatment access inequities in medicine.

What is the SMN2 gene and why does it matter?

SMN2 is a nearly identical paralogous copy of SMN1 — found on the same chromosome. Due to a single nucleotide difference in exon 7, SMN2 pre-mRNA is predominantly mis-spliced — producing approximately 90% truncated, non-functional SMN protein and only approximately 10% full-length SMN protein. The more SMN2 copies a person has, the more full-length SMN protein they produce, and the milder the SMA. Nusinersen and risdiplam work by correcting SMN2 splicing to increase the proportion of full-length SMN protein produced from SMN2.

How does GMJ News cover SMA?

GMJ News covers WHO SMA data, the nusinersen/risdiplam/zolgensma transformations, newborn screening evidence, the $2.125M zolgensma access crisis, pre-symptomatic treatment outcomes, and the SMA1 treatment window. SMA illustrates both the potential of gene therapy and the global health equity crisis in rare disease treatment access.

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Spinal Muscular Atrophy

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

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Spinal muscular atrophy (SMA) — the most severe genetic cause of infant death — affects approximately 1 in 6,000-10,000 births and was uniformly fatal in its most severe form (SMA type 1) within the first two years of life; it has been transformed into a treatable condition by three landmark treatments approved between 2016-2020: nusinersen (Spinraza, intrathecal ASO), onasemnogene abeparvovec (Zolgensma, single-dose gene therapy — at $2.125M the most expensive drug in history at approval), and risdiplam (Evrysdi, oral daily medication) (WHO). Newborn screening for SMA — enabling treatment before symptom onset — has become one of the most compelling cases for universal newborn genetic screening programmes.

Key messages

From fatal to treatable — three drugs 2016-2020

Spinal muscular atrophy has been transformed from the most common fatal genetic disease of infants to a manageable condition by three landmark treatments in just 4 years: nusinersen (2016), zolgensma (2019, $2.125M — most expensive drug at approval), and risdiplam (2020) (WHO).

SMA newborn screening — treat before symptoms

Pre-symptomatic treatment through newborn screening dramatically improves SMA outcomes — infants treated before neuromuscular deterioration begins achieve near-normal milestones. Many countries now include SMA in newborn screening panels.

SMN1 gene deletion

SMA is caused by deletion or mutation in the SMN1 (Survival Motor Neuron 1) gene on chromosome 5q — reducing SMN protein production. Without sufficient SMN protein, lower motor neurons in the spinal cord degenerate progressively.

SMA types 1-4 by severity

SMA type 1 (most severe, onset <6 months): never sits without support; ventilatory failure by 2 years without treatment. SMA type 2: never walks independently. SMA type 3: walks initially, may lose ambulation. SMA type 4 (adult onset): mild functional impairment.

Three treatment mechanisms

Nusinersen (Spinraza): intrathecal ASO increasing SMN2 exon 7 inclusion → more full-length SMN protein. Risdiplam (Evrysdi): oral small molecule also increasing SMN2 splicing. Zolgensma: AAV9 gene therapy delivering functional SMN1 copy into spinal cord motor neurons — one-time, potentially life-long correction.

Access inequality — $2M drug vs $100 treatment

The three approved SMA treatments cost $100,000-2,125,000 per patient — inaccessible to the majority of SMA patients in LMICs. Gene therapy (zolgensma) must be given by age 2 in SMA1 — a brief window that closes before most LMIC children are diagnosed.

Key statistics

~1 in 6-10K

live births affected globally

WHO

~1 in 50

people carry the SMN1 deletion (carrier frequency)

WHO

$2.125M

cost of zolgensma at 2019 FDA approval (most expensive drug)

Novartis/FDA

genetic cause of infant death before treatment era

WHO

distinct drug classes approved 2016-2020

FDA/EMA

Near-normal

milestones achievable with pre-symptomatic treatment

NEJM/research

SMA type distribution by age of onset and motor milestone

Source: WHO/SMA research. Type 1 most common and most severe; Type 4 rare and mild.

Glossary of key terms

SMN1 and SMN2 genes
WHO/ResearchSMN1 (Survival Motor Neuron 1): the gene whose deletion causes SMA. SMN2: a nearly identical paralogous gene — produces mainly truncated, non-functional SMN protein (approximately 90%) but some full-length SMN (approximately 10%). SMN2 copy number modifies SMA severity — more copies = milder disease. All SMA treatments aim to increase functional SMN protein from SMN2.

Nusinersen (Spinraza)
Biogen/FDA 2016An antisense oligonucleotide (ASO) — modifies SMN2 pre-mRNA splicing to include exon 7, producing more full-length functional SMN protein. Administered intrathecally (into spinal fluid) every 4 months for life after initial loading doses. FDA approved December 2016 — the first SMA treatment. Cost approximately $750,000-1M/year (year 1 highest).

Onasemnogene abeparvovec (Zolgensma)
AveXis/Novartis/FDA 2019An AAV9 gene therapy delivering a functional copy of the SMN1 gene into spinal cord motor neurons — a one-time IV infusion. FDA approved May 2019 for SMA patients under age 2. List price: $2.125 million — the most expensive drug ever approved at the time. Intended as a one-time cure; long-term durability data maturing.

Risdiplam (Evrysdi)
Roche/FDA 2020A small molecule SMN2 splicing modifier — taken as an oral liquid daily at home. FDA approved August 2020 for SMA in adults and children ≥2 months. Pharmacologically similar mechanism to nusinersen but orally available and reaching CNS systemically. Annual cost approximately $340,000 (less than nusinersen).

AAV9 gene therapy
ResearchAdeno-associated virus serotype 9 (AAV9) — used as the delivery vector for zolgensma because AAV9 efficiently crosses the blood-brain barrier (when given IV) and transduces spinal cord motor neurons. AAV9 gene therapy has transformed multiple neuromuscular diseases.

SMA newborn screening
WHO/ACMGTesting for SMN1 deletion/mutation from the routine heel-prick blood spot within days of birth — identifying SMA before neuromuscular deterioration begins. Pre-symptomatic treatment in SMA type 1 (when started before approximately 6 weeks of age) achieves sitting, standing and even walking in the majority — outcomes impossible in symptomatic infants.

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Spinal Muscular Atrophy

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