Spinal muscular atrophy is a rare genetic condition that weakens muscles over time, but recent breakthroughs in treatment are transforming the lives of those affected, offering new possibilities where there were once few options.

New Hope in Managing Muscle Weakness

Spinal muscular atrophy, commonly known as SMA, is a genetic disorder that affects the nerves controlling voluntary muscle movement. The condition arises when special nerve cells in the spinal cord called motor neurons gradually break down and stop working properly. Without these nerve cells, the signals that the brain sends to muscles cannot reach their destination, resulting in muscles that become weak and eventually waste away over time.^[1]

The treatment of SMA has undergone a revolutionary transformation in recent years. For decades, families affected by this condition had access only to supportive care aimed at managing symptoms and preventing complications. Today, the landscape has dramatically changed. Medical science has developed targeted treatments that address the underlying genetic cause of SMA, not just its symptoms. These treatments aim to slow disease progression, maintain or improve muscle function, and enhance quality of life for individuals across all types of SMA.^[5]

Treatment decisions depend on several factors, including the type of SMA diagnosed, the age when symptoms first appeared, the severity of muscle weakness, and the individual’s overall health status. Some people with SMA are diagnosed as infants, while others may not experience symptoms until adulthood. Because SMA presents differently in each person, healthcare teams customize treatment plans to match individual needs and circumstances.^[2]

The goal of treatment is not only to address the progressive muscle weakness but also to support breathing, nutrition, mobility, and overall wellbeing. Medical societies and expert panels have established clinical guidelines to help healthcare providers deliver comprehensive care. At the same time, researchers continue to investigate new therapies through clinical trials, expanding treatment options and improving outcomes for people living with SMA.^[4]

Standard Treatment Approaches

Until recently, standard treatment for spinal muscular atrophy focused entirely on managing symptoms and preventing complications rather than addressing the underlying genetic cause. This supportive care remains an essential component of comprehensive SMA management, working alongside newer disease-modifying therapies to provide the best possible outcomes.^[15]

Respiratory care represents one of the most critical aspects of SMA treatment. Because the muscles involved in breathing can weaken significantly, people with SMA often need respiratory support. This may include devices to assist coughing, breathing exercises, and in more severe cases, mechanical ventilation to help with breathing during sleep or throughout the day. Regular monitoring by respiratory specialists helps identify problems early and adjust support as needed.^[1]

Nutritional support is equally important because weakened muscles can affect swallowing and eating. Some individuals with SMA require modified diets with softer foods or liquids that are easier to swallow safely. A speech pathologist can evaluate swallowing function and the risk of aspiration, which occurs when food or liquid enters the airways instead of the stomach. When swallowing becomes too difficult or dangerous, a feeding tube may be recommended to ensure adequate nutrition and prevent complications.^[7]

Physical therapy and rehabilitation play a vital role in maintaining muscle strength, preventing joint stiffness, and preserving mobility. Therapists design individualized exercise programs that help people with SMA maintain the highest possible level of function without overworking weakened muscles. These programs often include stretching exercises to prevent joints from becoming fixed in one position, strengthening exercises for muscles that still have function, and mobility training.^[19]

Orthopedic management addresses bone and joint issues that commonly develop in SMA. The most frequent concern is scoliosis, an abnormal sideways curvature of the spine. Scoliosis can affect comfort, sitting balance, arm function, and most critically, breathing capacity. Treatment may include supportive bracing to slow curve progression or, in more severe cases, surgical correction to stabilize the spine. Other orthopedic interventions may address joint contractures or hip problems.^[19]

Assistive devices and mobility equipment help people with SMA maintain independence and participate in daily activities. Depending on the level of muscle weakness, this may include walkers, manual or powered wheelchairs, standing frames, or supportive seating systems. Occupational therapists work with individuals to identify equipment that supports their specific needs and goals.^[4]

The duration of supportive care is lifelong, as SMA is a chronic condition requiring ongoing management. The specific types of support and their intensity may change over time as the disease progresses or stabilizes, and as new disease-modifying treatments potentially alter the natural course of the condition. Families and individuals with SMA benefit from education about the condition and training in care techniques to maximize independence and quality of life.^[18]

Disease-Modifying Therapies Currently Approved

The landscape of SMA treatment changed dramatically starting in 2016 when the first disease-modifying therapy received regulatory approval. These medications target the genetic root cause of the disease rather than simply managing symptoms. Three such therapies are now approved and available in multiple countries, representing different approaches to increasing the production of the SMN protein, which motor neurons need to survive.^[13]

Nusinersen (Spinraza)

Nusinersen, marketed under the brand name Spinraza, was the first disease-modifying therapy approved for SMA. This medication works by modifying the SMN2 gene, a backup gene that produces small amounts of SMN protein. Nusinersen changes how the SMN2 gene is processed, allowing it to produce more functional SMN protein that motor neurons need to survive and work properly.^[15]

The medication is administered through intrathecal injection, which means it is injected directly into the fluid-filled space surrounding the spinal cord. This delivery method ensures the drug reaches the motor neurons in the spinal cord where it is needed most. The treatment begins with a loading phase consisting of four doses given over two months, followed by maintenance doses every four months for the remainder of the person’s life.^[5]

Nusinersen is approved for use in children and adults with SMA of all types, making it the broadest treatment option in terms of patient eligibility. The approval was based on two major clinical trials called ENDEAR and CHERISH. The ENDEAR trial enrolled infants with SMA aged seven months or younger and demonstrated significant improvements in survival and achievement of motor milestones compared to those who did not receive treatment. The CHERISH trial included children between two and twelve years old and showed improvements in motor function.^[15]

Common side effects of nusinersen include headache, back pain, and complications related to the injection procedure itself, such as discomfort at the injection site. Because the drug is administered into the spinal canal, there is a small risk of infection or bleeding, though these complications are rare when performed by experienced healthcare providers.^[6]

Onasemnogene Abeparvovec (Zolgensma)

Onasemnogene abeparvovec, sold as Zolgensma, represents a fundamentally different approach to treating SMA. This is a gene therapy, meaning it delivers a working copy of the SMN1 gene directly into the patient’s cells. The therapy uses a modified virus as a delivery vehicle to carry the functional gene into motor neurons, where it can begin producing the SMN protein that is missing or defective in people with SMA.^[12]

Zolgensma is administered as a single intravenous infusion, delivered through a vein over approximately one hour. This one-time treatment is intended to provide lasting benefit by establishing ongoing production of SMN protein from the newly delivered gene. The therapy is currently approved for children younger than two years of age who have genetic confirmation of SMA with certain genetic characteristics.^[15]

Clinical studies of Zolgensma have shown that treated infants achieve motor milestones such as sitting independently and walking that would not be expected in the natural course of severe SMA. Many treated children require less respiratory support and feeding assistance than historically seen in untreated SMA. The therapy has been most effective when given to infants before significant motor neuron loss has occurred, highlighting the importance of early diagnosis.^[16]

Because Zolgensma delivers genetic material, it can trigger immune system responses. To manage this, children receiving the therapy are given corticosteroid medications before and after the infusion to suppress the immune reaction. Side effects can include elevated liver enzymes, requiring monitoring of liver function through blood tests for several months after treatment. Some children experience vomiting or fever following the infusion. The most serious potential side effect is liver damage, which is why careful monitoring is essential.^[12]

Risdiplam (Evrysdi)

Risdiplam, marketed as Evrysdi, offers yet another mechanism for increasing SMN protein production. Like nusinersen, it targets the SMN2 gene, but risdiplam is a small molecule drug taken orally as a liquid medicine rather than requiring injections. This makes it the first SMA treatment that can be taken at home without medical procedures.^[5]

Risdiplam modifies how the SMN2 gene is processed throughout the body, increasing the amount of functional SMN protein produced not only in motor neurons but in other tissues as well. The medication is taken once daily, mixed with food or liquid for infants and young children, or taken directly from a syringe for those who can swallow it. Treatment continues daily for the long term.^[6]

This therapy is approved for individuals aged two months and older with SMA of all types. Clinical trials demonstrated improvements in motor function in both infants and older children treated with risdiplam. In the FIREFISH trial, which studied infants with Type 1 SMA, most treated babies achieved the ability to sit without support, something rarely seen in the natural course of this severe form. The SUNFISH trial in older children and adults showed slower decline or improvement in motor function.^[13]

Common side effects of risdiplam include fever, diarrhea, rash, mouth sores, and upper respiratory infections. Because the drug affects cells throughout the body, not just the nervous system, ongoing monitoring is recommended. The long-term effects are still being studied as the medication has been available for a shorter time than nusinersen.^[5]

Experimental Treatments in Clinical Trials

While three disease-modifying therapies are now approved and available, research continues actively to develop additional treatment approaches and refine existing ones. Clinical trials are ongoing worldwide to test new molecules, evaluate approved therapies in different patient populations, and explore combination approaches that might provide even greater benefit.^[13]

Understanding Clinical Trial Phases

New treatments progress through several phases of testing before they can be approved for general use. Phase I trials are small studies focused primarily on safety, determining what dose can be given safely and identifying potential side effects. Phase II trials expand to include more participants and begin evaluating whether the treatment appears effective while continuing to monitor safety. Phase III trials are large studies that compare the new treatment against standard care or placebo to definitively establish effectiveness and safety. Some clinical trials for already-approved SMA treatments continue as Phase IV studies, gathering additional information about long-term outcomes and use in specific populations.^[13]

Ongoing Research Directions

Researchers are investigating several promising approaches to SMA treatment that work through different mechanisms than currently approved therapies. One area of active research involves developing additional ways to increase SMN protein production or stability. Scientists are testing compounds that activate the SMN2 gene more strongly or prevent the SMN protein from breaking down once it is produced, potentially extending its activity in motor neurons.^[6]

Another research direction focuses on neuroprotection, which means protecting motor neurons from damage and death even when SMN protein levels remain low. These experimental therapies target the downstream effects of SMN deficiency, attempting to keep motor neurons alive and functioning through alternative pathways. While these approaches would not address the genetic root cause, they could provide additional benefit when combined with SMN-increasing therapies.^[6]

Muscle restoration strategies represent yet another avenue of investigation. Rather than focusing on motor neurons, these experimental treatments aim to strengthen muscles directly or prevent muscle wasting. Approaches being studied include drugs that promote muscle growth, reduce muscle breakdown, or improve the connection between nerves and muscles. If successful, these could complement treatments that protect motor neurons.^[6]

Gene therapy research continues beyond Zolgensma, with scientists exploring different viral vectors or delivery methods that might allow treatment of older children and adults who currently exceed age restrictions for the approved gene therapy. Researchers are also investigating gene editing technologies that could potentially correct the genetic defect directly in a person’s own cells rather than adding a new gene.^[6]

Several clinical trials are evaluating the three approved therapies in patient populations not included in the original pivotal studies. For example, studies are examining outcomes when treatment begins before birth, during pregnancy, or in adults with milder SMA types who were not represented in early trials. These studies help expand understanding of who benefits most from treatment and when it should ideally begin.^[13]

Trial Locations and Participation

Clinical trials for SMA treatments are conducted at specialized research centers around the world, including locations in the United States, Europe, and other regions. Trials are typically conducted at major medical centers with expertise in neuromuscular disease and experience caring for people with SMA. Eligibility requirements vary depending on the specific trial but generally include factors such as confirmed genetic diagnosis of SMA, age range, level of motor function, and sometimes specific genetic characteristics like the number of SMN2 gene copies.^[13]

People interested in participating in clinical trials can find information through several sources including their SMA care team, patient advocacy organizations such as the Muscular Dystrophy Association, and online clinical trial registries that list currently enrolling studies. Participation in a clinical trial means receiving experimental treatment that is not yet proven effective, along with close monitoring and frequent assessments. Potential participants should understand both the possible benefits and risks before enrolling.^[10]

Preliminary Results from Recent Studies

Early results from some ongoing clinical trials have shown promise. Studies combining different treatment approaches, such as using nusinersen in individuals already treated with gene therapy, are exploring whether multiple therapies together might provide greater benefit than either alone. Some preliminary data suggest that early combination approaches may improve motor outcomes beyond what single therapies achieve.^[13]

Trials of approved therapies in populations beyond their original approval, such as using risdiplam in adults or nusinersen in older individuals, have generally shown favorable safety profiles and some evidence of benefit in maintaining or improving function. These findings are helping to expand treatment options for people who previously had limited choices.^[13]

Research into biomarkers—measurable indicators of disease activity or treatment response—is also progressing. Scientists are working to identify blood tests, muscle measurements, or other markers that could help predict who will respond best to which treatment, potentially allowing more personalized treatment selection in the future.^[13]

Most Common Treatment Methods

• Gene-Targeted Therapies
  • Nusinersen (Spinraza) – modifies SMN2 gene processing through intrathecal injections given every four months after an initial loading period
  • Risdiplam (Evrysdi) – oral medication taken daily that modifies SMN2 gene processing throughout the body
  • Onasemnogene abeparvovec (Zolgensma) – one-time gene therapy delivered intravenously to provide a working copy of the SMN1 gene
• Respiratory Support
  • Mechanical ventilation devices to assist breathing during sleep or throughout the day
  • Cough assist devices to help clear airways and prevent respiratory infections
  • Breathing exercises and respiratory therapy to maintain lung function
  • Regular monitoring by pulmonologists to detect and treat breathing complications early
• Nutritional Management
  • Modified diet textures and consistencies for safe swallowing
  • Feeding tubes when swallowing becomes unsafe or inadequate for nutrition
  • Evaluation by speech pathologists for swallowing function assessment
  • Nutritional counseling by registered dietitians to optimize caloric and nutrient intake
• Physical and Occupational Therapy
  • Individualized exercise programs to maintain muscle strength without overworking weakened muscles
  • Stretching and range of motion exercises to prevent joint contractures
  • Mobility training and gait therapy for those able to walk
  • Assistive device training including wheelchairs, walkers, and adaptive equipment
• Orthopedic Interventions
  • Spinal bracing to slow progression of scoliosis and maintain sitting balance
  • Surgical correction of severe spinal curvature to protect lung function
  • Management of hip subluxation or dislocation through positioning or surgery
  • Treatment of joint contractures through splinting, casting, or surgical release