Spinal muscular atrophy (SMA) is a genetic disease that destroys the nerve cells responsible for controlling voluntary muscle movement. It affects roughly 1 in 5,000 newborns worldwide, making it one of the leading genetic causes of infant death. The disease ranges from a severe form that appears before birth to a mild adult-onset version, and three FDA-approved treatments have dramatically changed the outlook for many people diagnosed with it.
How SMA Damages Motor Neurons
SMA traces back to a single gene: SMN1, which stands for “survival motor neuron.” This gene produces a protein that motor neurons, the nerve cells running from the spinal cord to muscles, need to function and survive. In SMA, both copies of the SMN1 gene (one from each parent) are either deleted or mutated, so the body can’t produce enough of this critical protein.
Humans carry a near-identical backup gene called SMN2. The two genes differ by just a single letter in their genetic code, but that tiny change has an outsized effect: it causes SMN2 to produce a shortened, unstable version of the protein most of the time. A small fraction of SMN2’s output is the full-length, functional protein. That trickle is enough to keep a person alive but not enough to fully protect motor neurons from breaking down.
The number of SMN2 copies a person carries matters enormously. Someone with two copies produces less functional protein and typically has more severe disease. Someone with four or five copies produces more, and their symptoms tend to be milder. This copy-number variation is why SMA presents on a spectrum rather than as a single disease.
Without adequate SMN protein, motor neurons deteriorate in several ways. The junctions where nerves connect to muscles malfunction: nerve endings accumulate structural tangles, carry fewer chemical signals, and fail to properly communicate with muscle fibers. The neurons also lose incoming signals from sensory nerves and neighboring spinal cord cells. Over time, the motor neurons die, and the muscles they once controlled weaken and atrophy.
Types of SMA
SMA is classified into five types based on when symptoms first appear and the highest physical milestone a person achieves.
Type 0 (Congenital)
The rarest and most severe form. Reduced fetal movement is often noticeable during pregnancy, and infants are born with profound muscle weakness and respiratory failure. Most do not survive beyond the first month of life.
Type 1 (Severe Infantile)
About 60% of all SMA cases are type 1, also called Werdnig-Hoffmann disease. Symptoms appear within the first six months of life and include poor head control, very low muscle tone, difficulty swallowing, and weak breathing. Parents may notice quivering of the tongue (called fasciculations) and a feeble cry. Without treatment, children with type 1 rarely survive past age two.
Type 2 (Intermediate)
Symptoms develop between 6 and 18 months. Children with type 2 can learn to sit independently but never walk. Muscle weakness tends to affect the legs more than the arms, and involuntary muscle twitching and reduced reflexes are common. Breathing problems develop over time, and scoliosis is a frequent complication.
Type 3 (Juvenile)
Type 3 appears in childhood, typically after 18 months. Children learn to walk but may lose that ability later as weakness in the hips, thighs, and shoulders progresses. Breathing and swallowing problems are rare, and life expectancy is generally not reduced.
Type 4 (Adult)
The mildest form, appearing after age 21. The main symptom is gradual leg weakness. Most people with type 4 remain mobile throughout their lives, and it does not typically shorten lifespan.
Inheritance and Carrier Risk
SMA follows an autosomal recessive pattern, meaning a child must inherit a faulty SMN1 gene from both parents to develop the disease. In over 98% of cases, both parents are carriers: they each have one working copy and one defective copy, so they show no symptoms themselves.
When two carriers have a child, each pregnancy carries a 25% chance the child will have SMA, a 50% chance the child will be a carrier without symptoms, and a 25% chance the child will inherit two normal copies. In rare instances, a new mutation arises spontaneously in the egg or sperm, meaning only one parent is actually a carrier.
Newborn Screening and Diagnosis
All 50 U.S. states and Washington, D.C. now include SMA in their routine newborn screening panels. This is a significant milestone because the disease responds far better to treatment when caught before symptoms appear. A simple blood spot taken at birth can detect the SMN1 deletion, and a positive screen is followed by confirmatory genetic testing that also counts SMN2 copies to help predict severity.
Before universal screening, many infants were diagnosed only after parents noticed developmental delays, like failure to hold up the head, roll over, or sit. That delay cost precious time. Motor neurons lost before treatment begins cannot be recovered.
FDA-Approved Treatments
Three therapies are currently approved for SMA, each working through a different mechanism and route of delivery.
The first, nusinersen (sold as Spinraza), is injected directly into the spinal canal. It works by coaxing the SMN2 gene to include the normally skipped segment of its genetic code, boosting production of full-length, functional protein. Treatment begins with four loading doses over the first two months, followed by a maintenance injection every four months for the rest of the patient’s life.
The second, risdiplam (Evrysdi), works on the same principle of increasing functional protein from SMN2 but comes as a daily oral liquid or tablet. This makes it the most convenient option for long-term use, particularly for older children and adults.
The third, onasemnogene abeparvovec (Zolgensma), is a gene therapy delivered as a single intravenous infusion. It uses a harmless virus to deliver a working copy of the SMN1 gene directly into cells. Because the new gene is designed to persist, a single dose is intended to last a lifetime. It is approved for pediatric patients.
Clinical trials in young children with type 1 SMA have shown that these treatments reduce the need for breathing support and improve motor skills. The consistent finding across all three therapies is that earlier treatment produces better results. Infants treated before symptoms appear, identified through newborn screening, have achieved motor milestones like sitting and even walking that were previously unthinkable for their disease type.
Ongoing Physical and Respiratory Care
Medication addresses the root cause, but SMA also requires hands-on management of the muscles, joints, and lungs that are already affected.
Respiratory support is especially important for types 1 and 2. Many children use a bilevel positive airway pressure (BiPAP) machine during sleep to keep airways open and prevent dangerous drops in oxygen. Mechanical cough-assist devices help clear mucus from the lungs, reducing the risk of pneumonia. These proactive measures have been shown to extend survival and improve quality of life, sometimes allowing children to avoid a tracheostomy entirely.
Physical therapy focuses on stretching, positioning, weight-bearing exercises, and breathing exercises tailored to the individual. Starting rehabilitation early helps preserve existing motor and respiratory function, prevents joint contractures (where muscles shorten and stiffen around a joint), and delays or reduces the severity of scoliosis. For children with type 2, bracing or spinal surgery may eventually be needed to manage curvature of the spine.
Nutritional support matters too. Swallowing difficulties in types 1 and 2 can lead to poor weight gain and aspiration, where food enters the airway. Some children benefit from modified food textures or, in more severe cases, feeding tubes to ensure adequate nutrition.
Muscle-Targeting Therapies in Development
Current treatments all focus on increasing SMN protein levels, but a newer approach aims to strengthen muscles directly. A drug called apitegromab blocks a natural protein that limits muscle growth. In a trial across 48 hospitals in Europe and the U.S. involving 188 patients aged 2 to 21 with type 2 or type 3 SMA, children aged 2 to 12 who received the drug showed statistically significant improvement in motor scores compared to placebo. All participants were already on standard SMN-boosting therapy, suggesting the two approaches could complement each other. The drug is being developed as an injection given under the skin, though commercial availability is still several years away.