Spinal muscular atrophy treatment options
Medically reviewed by Natalie Katz, MD
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. The five main types — 0, 1, 2, 3, and 4, classified from the most severe form to the mildest — are caused by 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 starting treatment as early as 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. The 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 past 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.
Evrysdi is taken once a day, either as a flavored liquid by mouth or via feeding tube or as oral tablets. It is 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 protein. 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.
There are some concerns that Evrysdi can affect male fertility based on animal studies. Males interested in taking Evrysdi are encouraged to discuss this with their doctor.
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 (after an initial series of loading doses), the treatment boosts the ability of the SMN2 gene to produce more working SMN protein, similar to Evrysdi.
Laboratory evaluation is required before each injection to ensure proper healing following the injection.
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.
Administered intravenously (into the vein) through a single infusion, Zolgensma uses a modified and harmless viral shell 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 motor neurons 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
- Biohaven’s taldefgrobep alfa
- Roche’s GYM329 (RG6237).
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 into the lungs 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, well-fitting supports for the trunk and legs if using a wheelchair, and surgery to correct spinal deformities and improve breathing. Supplements of vitamin D and calcium may be prescribed to patients to improve bone health. In cases of very poor bone health or multiple broken bones, additional medications, called bisphosphonates, can be prescribed to further 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. As such, food consistency should be optimized and long fasting periods avoided.
Nutritional deficiencies may affect growth in children and further worsen muscle health. 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.
Occasionally, medications can be used to try and stimulate the appetite to increase calorie intake. Nutritional supplements such as shakes or high-calorie food additives can also be used to meet nutritional needs.
Whole-body vibration therapy
Whole-body vibration therapy (WBV) 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 stress, 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 a 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 type 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.
FAQs about SMA treatment
Gene therapy for spinal muscular atrophy (SMA) — currently limited to Zolgensma — involves using a modified virus to deliver a healthy copy of SMN1, the faulty gene in SMA, to patients. This is expected to significantly slow the progressive muscle weakness that characterizes the disease.
Among several therapeutic approaches now available, disease-modifying therapies (DMTs) show the greatest effects in terms of symptom reduction in spinal muscular atrophy (SMA). DMTs are able to slow or even halt disease progression. The therapies can help infants with SMA achieve otherwise unattainable motor milestones, and help older patients improve or maintain motor, breathing, and swallowing skills.
The cost of spinal muscular atrophy or SMA treatment is high, and depending on the insurance plan, some companies may provide coverage for disease-modifying therapies, while others won’t. Patients or caregivers should talk to their healthcare team and insurance providers about access to SMA treatments. Due to the Affordable Care Act in the U.S., denials or restrictions in health insurance, or higher premium rates because of a preexisting condition such as SMA, are prohibited.
Treatment for spinal muscular atrophy (SMA) is generally the same for children and adults, but doses of certain treatments may differ depending on age or weight. In addition, the use of Zolgensma, one of the three disease-modifying therapies available for SMA, is limited to children.
To date, no studies have directly compared the effects of disease-modifying therapies for spinal muscular atrophy (SMA). As such, no strong conclusions can be drawn about which treatment may be more effective. Evidence suggests that starting treatment early, especially prior to symptom onset, is more critical than DMT choice in achieving the best outcomes. SMA patients and/or their parents should talk to their healthcare team about eligibility for SMA treatments, and the potential risks and benefits of each therapy.
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