What is spinal muscular atrophy?

Spinal muscular atrophy (SMA) is a genetic condition that causes progressive weakness of muscles used for movement. The cause is loss of motor neurons (the nerve cells in the spinal cord that send signals to muscles). Without these signals, muscles do not work properly and gradually waste. SMA covers a wide spectrum from severe infant-onset disease to milder adult-onset disease.

The genetics. SMA is caused by a problem with a gene called SMN1, which makes a protein called SMN (survival motor neuron) that motor neurons need to function. Most patients with SMA have lost both copies of the SMN1 gene. Most people have one or more copies of a similar but less effective backup gene called SMN2; the number of SMN2 copies a person has helps determine the severity of their SMA.

The traditional outlook. Before 2016, there was no specific therapy for SMA. The most severe form (type 1, presenting in infancy) was typically fatal in the first two years of life. Less severe forms caused progressive disability. Care was supportive: respiratory support, nutritional support, physiotherapy, and management of complications.

The modern therapy. Three disease-modifying treatments have transformed the picture.

Nusinersen is given as injections into the spinal fluid, with loading doses followed by maintenance doses every four months. It increases the production of SMN protein from the SMN2 backup gene.

Onasemnogene abeparvovec is a one-time intravenous gene therapy that delivers a working copy of the SMN1 gene using a viral carrier. It is typically given to young children with weight-based dosing.

Risdiplam is a daily oral medicine that, like nusinersen, boosts SMN protein production from SMN2.

Newborn screening. SMA is now part of the standard newborn screening panel in most US states and in many other jurisdictions. Babies identified before symptoms appear can start treatment in the first weeks of life and typically achieve far better motor function than babies treated after symptoms develop.

The combination question. Gene therapy provides one-time SMN protein production from a delivered gene; the long-term durability of this benefit is being studied. Combination strategies (gene therapy plus chronic SMN-modifier therapy) are being investigated to extend lifetime benefit in patients who may not produce enough SMN protein from gene therapy alone.

What to expect. With early diagnosis through newborn screening and prompt treatment, most infants with SMA can achieve motor milestones close to typical development. For people diagnosed and treated symptomatically, modern therapy stabilises or improves muscle function and substantially improves outlook compared to the pre-2016 era.