Spinal Muscular Atrophy (SMA)

Spinal muscular atrophy (SMA) is a rare hereditary genetic condition in which muscles throughout the body are weakened because nerve cells in the spinal cord and brainstem do not work properly. SMA is the number one genetic cause of infant mortality.

There are four types of SMA:

• Type 1 is the most common and severe form of SMA. It’s sometimes called Werdnig-Hoffmann disease or infantile-onset SMA. Children with type 1 have limited movement, can’t sit without support, and have trouble breathing, feeding, and swallowing. Symptoms begin at birth or within the first six months of life. Many children with type 1 do not live past age 2.
• Type 2 is an intermediate form of SMA. Children with this type may sit without support at some point but cannot walk on their own. Symptoms typically start between 6 and 18 months of age. Depending on the severity of symptoms, children with type 2 may have a normal life span.
• Type 3 is a milder form of SMA. It’s also known as Kugelberg-Welander disease and resembles muscular dystrophy. While children with type 3 usually are able to walk, most have some difficulty walking. Some may eventually need to use a wheelchair. Symptoms usually appear around 18 months of age or in early childhood. Children with this type of SMA generally have an almost normal life expectancy.
• Type 4 is very rare. It usually starts in young adulthood, and causes mild motor impairment.

Symptoms of spinal muscular atrophy (SMA) vary greatly depending on the type. Children with the more serious form of SMA (Type 1) usually have more severe symptoms that are noticeable within the first six months of life. Those with milder forms have less severe symptoms that may not be noticeable until the child is 18 months or older.

Symptoms of SMA may include:

• Muscle weakness and decreased muscle tone
• Limited mobility
• Breathing problems
• Problems eating and swallowing
• Delayed gross motor skills
• Spontaneous tongue movements
• Scoliosis (curvature of the spine)

SMA is an autosomal recessive disease. This means that (most of the time) both parents must carry the genetic mutation for a child to have the condition.

The gene affected in SMA is the “survival of motor neuron” gene (SMN1 and SMN2). In 95 percent of SMA cases, both copies of the SMN1 gene are missing. All people with SMA have a number of copies of the SMN2 gene. But the SMN2 gene produces only a small amount of functional SMN protein; the more copies of the SMN2 gene a child has, the milder the disease.

If someone in your family has SMA, your chance of being an SMA carrier significantly increases. When both parents are carriers, there is a 1 in 4 (25 percent) chance with each pregnancy that they will have a child with SMA.

SMA is sometimes difficult to diagnose, as symptoms can resemble other conditions or medical problems. Doctors usually diagnose SMA after a child has muscle weakness and decreased muscle tone.

If your clinician suspects SMA, they may use the following tests to diagnose the condition:

• Genetic blood tests, which can confirm the diagnosis of SMA
• An electromyography (EMG) test that measures the electrical activity of a muscle or a group of muscles (in some cases)
• A creatine kinase (CPK) test (to distinguish from other types of neuromuscular diseases, if necessary)

As yet, there is no complete cure for SMA. However, the discovery of the genetic cause of SMA has led to the development of several treatment options that affect the genes involved in SMA — a gene replacement therapy called Zolgensma, and two drugs, called nusinersen (Spinraza) and risdiplam (Evyrsdi). All three treatments were tested in clinical trials at Boston Children’s Hospital and elsewhere prior to their approval by the U.S. Food and Drug Administration (FDA).

You and your child’s care team will decide together the most appropriate treatment plan based on several factors:

• Your child’s age, health, and medical needs
• SMA type
• Extent and type of symptoms
• Ability of your child to tolerate procedures and treatments
• Family preferences

Gene therapy for SMA (Zolgensma®)

Boston Children’s is one of the first pediatric hospitals in the nation to offer an FDA-approved gene therapy for the treatment of spinal muscular atrophy in children less than 2 years of age. Known by the brand name Zolgensma®, this gene therapy prevents further motor neuron and muscle degeneration by replacing the defective or missing SMN1 gene.

Known formerly as AVXS-101, this one-time gene therapy treatment replaces the defective or missing gene (SMN1), which is responsible for making the survival motor neuron (SMN) protein. Providing a functional copy of SMN1 prevents motor neurons and muscles from degenerating further.

Before receiving the gene therapy, children first have blood tests to make sure patients qualify for the treatment. Zolgensma® is given through an intravenous (IV) infusion at our treatment center. The infusion takes about one hour.

For more information about SMA gene therapy or to refer a patient, contact the Spinal Muscular Atrophy Program at 617-919-6814.

Risdiplam (Evrysdi)

Since 2016, Boston Children’s Spinal Muscular Atrophy Program has been actively involved in the key clinical trials for risdiplam (brand name Evrysdi), the first oral drug treatment for SMA. Risdiplam is the third treatment for SMA and was FDA approved in 2020 for use in children 2 months and older.

Our team is among the researchers involved in the ongoing FIREFISH trial, which provided some of the clinical information leading to ridsiplam’s FDA approval. This trial, and others we participate in, will continue to investigate risdiplam in participants for several years.

Nusinersen (Spinraza)

Our program was also involved in clinical trials of nusinersen (brand name Spinraza), the first drug treatment for SMA. We were the first hospital in the world to enroll an infant with type 1 SMA in the phase 3 ENDEAR trial in 2014.

Due to the success of clinical trials, the FDA approved the use of nusinersen for SMA in children and adults in 2016, and we began offering the drug to all eligible SMA patients. Our multispecialty SMA team helped to develop standardized ways to measure patients’ SMA symptoms and the changes in these symptoms over time. These results are being used to measure the effectiveness of nusinersen and other treatments.

The Spinal Muscular Atrophy Program at Boston Children’s Hospital brings together a team of experts from different specialties experienced in caring for children with SMA. We hold a dedicated SMA clinic once or twice a month so that your child can receive all of their SMA-related care in a single visit. This approach means that our various specialists can all work closely with your family to make sure your child’s care is well coordinated. Our program offers several therapy choices, including gene therapy, for SMA.