Patient Guide to Spinal Muscular Atrophy

Spinal Muscular Atrophy: Treatment

New treatments for spinal muscular atrophy (SMA), such as risdiplam, offer hope for many people with this disease.

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When you learn your child has or will be born with spinal muscular atrophy (SMA), you’re not going to just accept it. You’re going to fight, and now you can fight with more effective weapons than ever before.

When you learn your child has or will be born with spinal muscular atrophy (SMA), you’re not going to just accept it. You’re going to fight, and now you can fight with more effective weapons than ever before.

SMA treatmentYou can deploy powerful new weapons in the fight against SMA.

New treatments for spinal muscular atrophy offer hope for many people with this disease. These treatments are the first that target the underlying cause of SMA disease, and may be able to prevent the disease from developing or getting worse:

  1. Nusinersen (Spinraza) is approved for of all types of SMA.1
  2. Onasemnogene abeparvovec-xioi (Zolgensma) is a gene therapy approved for children up to age 2 years.2

Another agent—risdiplam—is awaiting approval by the U.S. Food and Drug Administration.3

“It is a privilege and extremely gratifying to be able to participate in these life-changing treatments and see a disease that was formerly deadly convert into a disease that people can live with and thrive with,” said Claudia A. Chiriboga, MD, MPH, Professor of Neurology and Pediatrics at Columbia University Medical Center in New York, NY. “Before December 2016, there was nothing on the horizon for SMA treatment. Now, we have two, and possibly soon three SMN-modifying treatments that are likely to be life altering for many people with SMA.”

It is important to start these treatments as soon as possible after SMA disease diagnosis. This section provides more information on these treatments as well as supportive therapies, but as always, talk to your doctor to see which treatment is right for you or your child.

To understand how the new treatments work, here is a quick reminder of what causes SMA:

  • SMA is caused by defects (mutations or deletions) in the SMN1 and SMN2 genes, causing these genes to produce low levels of survival motor neuron (SMN) protein.
  • SMN protein helps keep motor neurons (nerves responsible for movement) in the brain and spinal cord healthy.
  • Without enough SMN proteins, motor neurons die and muscles become weak.

Nusinersen

Nusinersen was approved in 2016 for all types of SMA. The drug targets the SMN2 gene to increase production of SMN proteins. Nusinersen is injected into the fluid surrounding the spinal cord and is first given as four injections over two months, followed by one injection every four months for life.1 Nusinersen may be most effective when given early, especially in babies and children.

Nusinersen was approved by the US Food and Drug Administration (FDA) based on findings from a clinical trial in which 51% of babies with symptoms of SMA type 1 treated with this drug showed significant improvement in motor function, including:

  • Head control
  • Rolling
  • Kicking
  • Crawling
  • Standing
  • Walking

…compared with none of the babies given placebo (no drug). The babies were all 7 months of age or less at the time of their first treatment.

Nusinersen also showed benefit in a study involving older children ages 2 to 9 years who showed symptoms after 6 months of age, the majority of whom had SMA type 2.

“Improving function at any level and offering the hope of stabilizing the disease is in itself life altering for many of our patients,” Dr. Chiriboga notes. If a treatment can preserve a person’s ability to swallow or use their arms, the benefit may outweigh the risk. Maintaining arm control may allow people to use a keyboard and continue to go to school or work, she says. 

The medication is considered safe and well-tolerated, with side effects mostly being related to how the drug is given, according to Dr. Chiriboga. A needle is placed into the spinal canal, and can leave a tiny hole that allows spinal fluid to leak out, which in turn can lead to severe headaches.1

The injection may be hard to perform in people with severe scoliosis or who have undergone scoliosis surgery, Dr. Chiriboga notes. Respiratory tract infections and constipation also may occur in babies.1 Additionally, there is an increased risk of bleeding and kidney problems.1 Talk to your doctor about these potential side effects and how to look out for them.

Onasemnogene

Gene therapy with onasemnogene abeparvovec-xioi was approved in 2019 for the treatment of SMA in babies and children younger than 2. Onasemnogene works by replacing the defective or missing SMN1 gene with a working copy. The treatment is given by a one-time intravenous infusion (injection into a vein), and can be given before symptoms start.   

FDA approval of onasemnogene was based on two clinical trials involving babies who showed symptoms of SMA before 6 months of age. In the first study, all 15 of those given onasemnogene were alive and did not need mechanical ventilation to help them breathe when they were at least 20 months of age.

Spinal muscular atrophy treatment gene therapyOnasemnogene is gene therapy.

In comparison, only 8% of babies who are left untreated survive at this age. Many of the children given gene therapy were able to sit, roll, crawl, and eat oral foods and speak, and two could walk. These benefits were still found at 5 years following treatment.4

Similar findings were noted in the second clinical trial, in which nearly all of the children were alive and did not need mechanical ventilation at 14 months after receiving treatment, and more than half were able to sit for at least 30 seconds without help at 18 months of age.4

“Onasemnogene is very effective in symptomatic infants who are treated early in their disease,” Dr. Chiriboga says. Even better results have been found in babies treated before they have symptoms, she adds.4 Researchers are also testing whether gene therapy is beneficial when given in older children (up to age 5) age who can sit but not stand or walk.

Initially, the treatment may cause temporary injury to the liver that may require use of steroids. Bleeding is also a risk with gene therapy.2 Additionally, a marker of heart damage sometimes temporarily rises in people receiving gene therapy. While it is unclear what exactly this increase means, it does require monitoring.2

Since gene therapy is given once and then stays in your body, there is no way to alter the treatment if long-term side effects occur, Dr. Chiriboga notes. However, in babies who, based on SMN2 copy number, are likely to develop severe disease, “any unforeseen complications are worthwhile because the benefit is extraordinary,” she says.

Risdiplam

Risdiplam works by promoting production of SMN protein from the SMN2 gene. Risdiplam is currently awaiting FDA approval. 

A clinical trial of risdiplam found an “excellent response” when given to children ages 1 to 7 months with symptoms of SMA type 1, which is especially noteworthy as these infants were on average older at study entry than infants included in other studies, Dr. Chiriboga says.3 The survival rate was 93% after 1 year of treatment, and about one-third of children were able to sit without help for at least 5 seconds.3

“After 12 months of treatment, many risdiplam-treated infants were sitting with and without support. Importantly, nearly all (about 95%) of the children maintained their ability to swallow, and 90% of them were able to feed orally, which is really striking,” Dr. Chiriboga says.3

A second trial found benefit after 1 year of treatment in patients 2 to 25 years of age with SMA type 2 or 3 compared with placebo.5 As expected, the benefits were greatest in younger people; however, disease stabilization (symptoms did not worsen) was found in people ages 18 to 25 years. Risdiplam also is being studied in people with SMA ages 6 months to 60 years who previously used other SMA treatments.6

The most common side effects of risdiplam in these trials were upper respiratory tract infection, pneumonia, fever, constipation, and cold symptoms.5,6 In some cases, pneumonia can be severe, and in rare cases, people developed lung infection, respiratory failure, and decreased muscle tone.5,6

Risdiplam will be an important option for adults, many of whom have not decided to treat with nusinersen because it has not been studied in adults or because they are not given the option by their insurance provider or physician, Dr. Chiriboga notes. The ease of an oral agent is also beneficial, she says.

Supportive Therapies

Spinal muscular atrophy treatments care planAn SMA care plan

Supportive therapies help preserve muscle strength, level of functioning, and ability to swallow and breathe in people of all ages with SMA. Your doctor will work with you to build a team of specialists involved in various areas of SMA care. These specialists will work together—and with you and your family—to offer the best opportunity to achieve long-term good outcomes and quality of life.

  • Lung care: Pulmonologists can help patients exercise their lungs to improve breathing and clear their airways. In people with breathing problems, devices that help with breathing may be used, including noninvasive positive pressure ventilation.
  • Physical therapy/occupational therapy: Therapists will teach people with SMA and their families stretching and exercises to help maintain muscle strength and flexibility. Physical therapists primarily work with the legs and feet, while occupational therapists help with fine motor skills in the arms and hands.
  • Orthopedic care: These specialists address musculoskeletal issues caused by SMA, such as contractures, hip dislocation, and scoliosis, using bracing and stretches among other therapies.
  • Spine care: Bracing may stop scoliosis (curving of the spine) from getting worse, but some people need spine surgery to keep the spine straight to make it easier to breathe and sit as well as to improve their quality of life.
  • Nutrition: A dietician or gastrointestinal (GI) specialist can make sure a person with SMA is getting enough nutrients, and can help with gastric reflux and constipation. In babies with SMA who have swallowing problems, eating too little can lead to poor growth. On the other hand, maintaining a healthy weight is hard in people with SMA who can’t sit or walk, and added weight can make it even harder to move. If swallowing food is no longer a safe option, a GI specialist may recommend delivering nutrients directly to the stomach using a gastrostomy tube.   
  • Lifestyle considerations: Bracing and supports may be used to help keep a good posture for breathing and eating. Wheelchair accommodations for the house and car, as well as devices to help move around in daily life—including getting out of bed and going to the bathroom—are helpful. These include a Hoyer lift, custom bed, bath chairs, standers, and special strollers. Eye tracking devices may help people communicate if they cannot speak or use a keyboard.

Where to Get Treatment

“Ideally, neuromuscular centers are most advantageous for offering SMA care, as providers are updated on the latest treatments and can provide a variety of rehabilitation services in one place so treatment is not fragmented,” Dr. Chiriboga notes. These centers also limit the burden on caregivers and patients in terms of travel and taking time off of work, and especially in people with mobility issues. In addition to treatment from a neurologist, these centers provide genetic counseling, physical/occupational therapy, pulmonology, orthopedic care, respiratory care, and nutritional care.

If you do not live near a neuromuscular center, find a neuromuscular specialist or neurologist experienced in SMA who can begin treatment immediately. This provider can direct you to other local health care practitioners who provide over services needed to help people with SMA live with the best quality of life.

Updated on: 10/19/20
Khoi D. Than, MD
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Spinal Muscular Atrophy: What You Need to Know

Spinal muscular atrophy (SMA) is an inherited disease that causes weakness and wasting (break down) in muscles that control movement and breathing. Learn the causes, symptoms, and new treatments for SMA.
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