Spinal muscular atrophy treatment options

Last updated Feb. 2, 2023, by Marisa Wexler, MS
Fact-checked by Ana de Barros, PhD

There are several treatment options available for spinal muscular atrophy (SMA), a rare genetic condition characterized by progressive muscle weakness and wasting. The disease mainly affects motor function, but many patients also may experience breathing, swallowing, and speech difficulties, along with bone defects and other symptoms.

The age of onset, occurrence, and severity of SMA symptoms vary across, and even within, the different types of the disease. Its five main types — 0, 1, 2, 3, and 4, classified from the most severe form to the mildest — are caused by no to low levels of a protein called survival motor neuron (SMN), due to mutations in the SMN1 gene.

While no available SMA treatment can cure the disorder, disease-modifying therapies (DMTs), or those targeting the underlying cause of the disease, have the potential to slow or halt SMA progression.

It is well-established that initiating treatment at the earliest time possible, preferably before symptom onset, is key for achieving best outcomes and reducing the overall SMA treatment cost.

The type of treatments a patient may need depends on the severity of symptoms and should be determined together with a team of healthcare professionals. Latest standard of care recommendations for SMA emphasize the importance of a multidisciplinary approach, involving several healthcare specialists, including neurologists, pulmonologists, dietitians, orthopedists, and physical therapists.

Drug therapies

There has been huge development in SMA treatment options in the last decade.

Three disease-modifying therapies are available for SMA. They all have been shown to help infants achieve otherwise unattainable motor milestones, and to improve or maintain motor, breathing, and swallowing skills in older patients.

While all three DMTs work to increase the levels of the SMN protein, they do so through different mechanisms and involve distinct routes of administration.

Evrysdi

Evrysdi (risdiplam) is the first at-home and oral treatment approved for all main types of SMA. In the U.S., the therapy is available for patients of all ages, while in other regions, its indication is limited to those 2 months and older.

A flavored liquid, Evrysdi is taken once a day by mouth or via a feeding tube. It comprises a small molecule designed to increase the production of working SMN protein by the “backup” SMN2 gene, which in normal conditions can only produce up to 15% of functional SMN. A higher number of SMN2 copies is associated with milder SMA types.

Roche and its subsidiary Genentech, which developed Evrysdi in collaboration with PTC Therapeutics and the SMA Foundation, are marketing it.

Spinraza

Spinraza (nusinersen), by Biogen, was the first disease-modifying therapy approved for all main SMA types. It is indicated for children and adults, and is administered directly into the spinal canal, which is filled with cerebrospinal fluid, the liquid surrounding the brain and spinal cord.

Given every four months, the treatment boosts the ability of the SMN2 gene to produce more working SMN protein.

Zolgensma

Zolgensma (onasemnogene abeparvovec-xioi) is a one-time gene therapy approved in the U.S. to treat all main types of SMA in children up to age 2.

The Novartis gene therapy also is available in other markets, though the specific type(s) and age ranges for treatment vary across regions. In Europe, use of Zolgensma is limited to children with up to three SMN2 gene copies and weighing up to 21 kilograms (about 46 pounds). It could cover children up to age 5 with types 0 to 3.

Administered directly into the bloodstream (intravenously) through a single infusion, Zolgensma uses a modified and harmless virus to deliver a healthy copy of the SMN1 gene to cells. While the gene is not introduced into the patient’s DNA, it is expected to be maintained inside cells that do not divide into new cells, such as the nerve cells that regulate voluntary movement and progressively die without SMN.

Experimental treatments

A number of experimental therapies are being developed for the main types of SMA. These range from potentially new DMTs, such as Biogen’s Spinraza-like therapy BIIB115, to add-on treatments focused on alleviating SMA symptoms.

For targeting disease symptoms, several investigational muscle-directed therapies are under development, which could complement existing DMTs. These include:

• Scholar Rock’s apitegromab
• reldesemtiv, from Cytokinetics
• Roche’s GYM329 (RO7204239).

Symptom management and supportive therapies

There are a number of symptom management and supportive interventions people with SMA can use, in addition to DMTs, to maximize their ability to function in daily life. While DMTs address the root cause of SMA, these supportive therapies also can help in managing disease symptoms day to day.

Physiotherapy

Given the known beneficial effects of exercise in maintaining muscle health, SMA patients are often recommended to incorporate physical activity into their daily routine. A physiotherapist can help create an exercise program that’s tailored for the patient’s capacity and needs, as well as offer guidance about mobility devices or other adaptive equipment.

Consisting of exercises and stretching, physiotherapy, or physical therapy, may help maintain and improve muscle strength, range of motion, posture, and flexibility in people with SMA. Besides leg/arm movement, rehabilitative therapies may focus on exercises to improve breathing, coughing (for clearing the chest), chewing, and swallowing.

Respiratory support

SMA can weaken the muscles supporting the chest wall, ultimately leading to breathing difficulties and inefficient coughing and clearance of lung secretions — which increase the risk of lung infections.

Patients with breathing difficulties should be followed by a pulmonologist to monitor the condition and guide treatment. Such treatment may involve medication or specialized equipment. Respiratory support can be either noninvasive or invasive.

Noninvasive ventilation uses a mouth and/or nose mask connected to a bi-level positive pressure, or BiPAP, machine. Cough assist machines also may be used at home to clear mucus and other secretions in the respiratory tract. In invasive respiratory support, a tube is inserted either from the mouth or through a small incision in the neck.

Scoliosis treatment and bone health

The muscle weakness that characterizes SMA also can cause bone and joint problems. Among them are scoliosis, an abnormal and progressive sideways curvature of the spine, hip dislocation, joint contractures, and weak and fracture-prone bones.

Strategies to manage scoliosis include upper back and/or neck braces to help support the ribs and spine, and surgery to correct spinal deformities and improve both mobility and breathing. Supplements of vitamin D, which promotes calcium absorption, also may be prescribed to patients to improve bone health.

Nutrition

SMA patients, especially those with more severe types, may experience nutritional problems. This is due not only to weakness of the muscles that control chewing and swallowing, but also to gastrointestinal and metabolic issues.

Nutritional deficiencies may affect growth in children and further worsen muscle health. As such, food consistency should be optimized and long fasting periods avoided.

Conversely, reduced mobility may lead to weight gain. In these cases, patients are advised to consult with a nutritionist or other dietary specialist familiar with the nutritional needs of SMA patients to optimize their diet and energy intake. Diet also may be modified to help reduce some gastrointestinal symptoms.

For individuals with more severe muscle weakness, a feeding tube may be used to ensure the patient can get adequate nutrition. This involves delivering nutrients via a tube either passed through the nose or mouth into the stomach, or surgically fitted into the stomach through an opening made in the abdomen.

Whole-body vibration therapy

Called WBV for short, whole-body vibration therapy consists of promoting reflex-based, involuntary muscle contractions through a vibrating platform.

During a session of WBV, the person sits or lies on a vibrating platform that sends energy to the body, forcing muscles to contract and relax dozens of times per second.

This intervention may be combined with rehabilitative therapies to strengthen neuromuscular connections and ultimately improve motor function and mobility. Such strategies also may reduce bone loss in people with SMA.

Speech therapy

Speech therapy can help SMA patients overcome problems with speech and swallowing that develop due to weakness in the tongue, throat, and respiratory muscles.

Such therapy should be tailored for each patient, and may involve exercises to strengthen the muscles involved in speech and swallowing. The aim of speech therapy is to improve vocalization and speech quality in coordination with breathing.

Speech therapists also may recommend the use of aids and devices to help patients communicate more effectively.

Occupational therapy

The goal of occupational therapy in SMA is to develop strategies that maintain or increase patients’ independence in specific everyday tasks, such as dressing, bathing, handling utensils, or writing.

This may involve using specialized assistive equipment like standers and braces for the arms and legs, orthotics (shoe inserts to improve walking ability), adaptive strollers and wheelchairs, and speech synthesizers.

Occupational therapists also may recommend modifications to improve accessibility at home, work, and in school. Among possible modifications are ramps, mechanical lifts, shower chairs, and widening of doorways for wheelchair access.

Emotional support

An SMA diagnosis can take a toll on the mental health of patients and their families. Children and adults with SMA may experience developmental and emotional problems, such as anxiety and depression, difficulties in coping with stresses, low self-esteem and self-confidence, and social isolation.

Psychologists, as well as in-person and online support groups, can help to provide counseling and guidance to manage these psychological and social problems. Coping mechanisms that may help SMA patients include building connections with friends and family, maintaining optimism, practicing mindfulness, eating well, and exercising.

Does SMA treatment increase life expectancy?

In terms of life expectancy, which varies between SMA types, data collected so far support the beneficial effects of DMTs for children with the severe SMA type 1. Without treatment, these children would not live past age 2, but most of those starting DMT early on have so far survived into childhood, and some have shown typical motor development.

Because type 2 patients may survive into adulthood without treatment, and those with type 3 or 4 have generally normal life expectancies, there isn’t enough data yet to assess how much DMTs have prolonged the lives of these patients.

Longer-term findings are needed to draw strong conclusions about the efficacy of DMTs at extending the lives of people with any type of SMA.

SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.