What to know about SMA gene therapy

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SMA damages motor neurons in the brain and spinal cord. This can affect movement, breathing, growth, and development.

Damage to the SMN1 gene, which makes the survival motor neuron protein, causes SMA. SMA is an inherited disorder and is autosomal recessive. This means that a person must inherit two copies of the abnormal gene — one from each parent — to develop symptoms.

Gene therapy attempts to replace the affected SMN1 gene with a working copy. This can prevent further damage to motor neurons, stopping the progression of SMA.

In some infants, this treatment can be lifesaving. It can also prevent future mobility difficulties or stop existing disabilities from getting worse.

Gene therapy may mean that infants hit developmental milestones in, or close to, typical time frames.

In people who respond to gene therapy, the treatment can help by stopping:

• the development of new symptoms
• the worsening of existing symptoms
• the progression of the condition

Researchers have not tested gene therapy in children with advanced SMA and have not shown that gene therapy can reverse existing SMA symptoms.

However, the benefits of treatment can include:

• more typical development
• longer survival, including a reduction in premature death
• development of motor skills that a person might not have otherwise

A 2017 clinical trial involving 15 infants with SMA who were unable to sit independently found that gene therapy enabled 11 of the infants to sit by themselves. Additionally, all participants were alive at 20 months in comparison with an expected survival rate of 8%.

However, side effects can occur. In a 2021 study, all participating infants experienced elevated liver enzymes but remained asymptomatic. One participant experienced vomiting.

Only one form of gene therapy for SMA is currently available. Onasemnogene abeparvovec-xioi is a Novartis drug only available under the brand name Zolgensma.

The Food and Drug Administration (FDA) has only approved this gene therapy for children under the age of 2 years. Healthcare professionals will give this therapy as a single dose IV infusion. Children may need to take oral corticosteroids before and after the treatment.

The FDA has approved Zolgensma for children under the age of 2 years. To be eligible for the treatment, a child must meet certain criteria. These include:

• having genetically confirmed SMA
• being under the age of 2 years
• having sufficiently low levels of AAV9 antibodies
• having no known risk factors that make gene therapy unsafe

Zolgensma uses a modified adenovirus as a highly efficient vector to deliver a functioning copy of the SMN1 protein-coding gene directly into cells of the brain and spinal cord.

Research into additional therapies for SMA is ongoing.

The drug risdiplam (Evrysdi), which is the first oral SMA treatment, has gained approval in the United States and some European countries. The drug triggers the production of more SMN2 protein in the body. This protein is similar to SMN1 and can help prevent some of the damage a faulty SMN1 gene causes.

Another non-gene therapy treatment available for SMA is nusinersen (Spinraza). This injectable drug promotes typical SMN2 production and increases the amount of functional SMN protein that the body produces.

Researchers are also testing and developing other potential disease-modifying agents that might slow or reverse some of the effects of the faulty SMN1 gene.

Zolgensema is reportedly the most expensive drug in the world, costing $2.125 million for a single injection.

Other treatments are also costly, with nusinersen costing $118,000 per vial and about $708,000 for the first year of treatment.

Insurance

Some private insurance companies may cover part or all of the cost if a person meets their criteria. Different states’ Medicare policies may also cover part or all of the cost.

However, it is important for a person to check with their insurance company to ensure that they meet the criteria for coverage.

Find a list of insurers who cover gene therapy for SMA here.

Funding

Zolgensema is very expensive. However, the Patient Access Network (PAN) Foundation offers financial help for people who require treatment.

The PAN Foundation allows people to claim up to $6,500 per year if they satisfy the following criteria:

• receiving treatment for SMA
• living and receiving this treatment in the U.S.
• having health insurance that covers the treatment
• requiring a medication on PAN’s covered medication list
• having an income at or below 400% of the Federal Poverty Level

People can find out how their income compares with the Federal Poverty Level either on the PAN Foundation’s website or through the Office of the Assistant Secretary for Planning and Evaluation.

The PAN Foundation does not require applicants to be U.S. citizens, but all funding is subject to availability.

If a person does not qualify for the PAN Foundation’s financial assistance, they can explore the list of other funding options that the foundation provides.

Gene therapy for spinal muscular atrophy can increase survival rates and reduce or stop the progression of this condition. Currently, the only available form of gene therapy is Zolgensma, which is only suitable for children under 2 years of age.

People should contact a healthcare professional to discuss whether gene therapy is available in their area and whether it might be beneficial. Although this therapy is expensive, some insurance providers will help with the costs. The PAN Foundation also offers funding subject to eligibility criteria.