What is spinal muscular atrophy (SMA)?

SMA is a progressive, rare genetic disease that is caused by a survival motor neuron 1 (SMN1) gene that is missing or not working properly. Learn more about how SMA is inherited, the role of the backup gene, and the signs and symptoms of SMA.

Download the Facts About SMA guide

What is spinal muscular atrophy (SMA)?

SMA is a progressive, rare genetic disease that is caused by a survival motor neuron 1 (SMN1) gene that is missing or not working properly. Learn more about how SMA is inherited, the role of the backup gene, and the signs and symptoms of SMA.

Download the Facts About SMA guide
  • Number 1

    SMA is a progressive, rare genetic disease, yet it is the number one genetic cause of infant death.

  • About 1 in 50

    people in the United States (or 6 million* Americans) is a genetic carrier of SMA, and most don’t know it.

  • 1 in 10K

    SMA affects about 1 in every 10,000 babies born each year.

How SMA is inherited

SMA is an autosomal recessive disorder. This means a person must inherit one copy of a nonworking or missing gene from each parent to have the disease.

Parents who don’t have SMA but are carriers
25%
chance your child doesn’t have SMA and is not a carrier
50%
chance your child doesn’t
have SMA but is a carrier
25%
chance your child has SMA

What causes SMA?

The genetic root cause of SMA is an SMN1 gene that is missing or not working properly. When this main gene is missing or not working properly, the body cannot make enough survival motor neuron (SMN) protein, which is needed for motor neuron cell survival. Motor neuron cells are responsible for communicating with the muscles and telling them to work properly. A person is born with a certain amount of these cells. Without enough SMN protein, motor neuron cells become weaker and weaker and eventually stop working, lose all function, and die. As a result, things many of us take for granted, like breathing, eating, speaking, and lifting the head, become difficult.

Once motor neuron cells die, they cannot be brought back.


The role of a backup gene

There is a backup gene for the SMN1 gene, called the SMN2 gene. People can have one or more copies of this backup gene. This gene, like the SMN1 gene, tells the body to make SMN protein. For people with SMA, the SMN2 gene is the only source of SMN protein; however, it is unable to produce as much protein as the SMN1 gene.

In fact, the SMN2 gene makes only about 10% of working protein compared to the protein produced by the SMN1 gene.

Even people with several copies of the SMN2 gene may not produce as much SMN protein as those with the working SMN1 gene, and their motor neuron cells may not work as they should. Usually, the more copies of the SMN2 gene a person has, the less severe his or her SMA is.

Learn about the types of SMA
Genetics of a person unaffected by SMA with a working SMN1 gene
Genetics of a person living with SMA with a nonworking or missing SMN1 gene
HOW ZOLGENSMA WORKS

See how ZOLGENSMA provides the body with a new, working copy of a human SMN gene.

Read the transcript

NARRATOR: A dedicated team of scientists has developed a targeted approach for treating spinal muscular atrophy using a one-time-only gene therapy called ZOLGENSMA® (onasemnogene abeparvovec-xioi).

Gene therapy targets the genetic root cause of spinal muscular atrophy, or SMA, by replacing the function of the nonworking or missing gene that causes SMA, called the survival motor neuron 1 gene, or SMN1 gene. The SMN1 gene is very important because it’s the body’s main source for making SMN protein. SMN protein is used throughout the body, and it is essential to motor neuron cell survival.

Motor neuron cells are responsible for communicating with the muscles and telling them to work properly. In addition to the SMN1 gene, the body also has a backup gene called the SMN2 gene. People can have one or more copies of this backup gene. In a person with SMA, the SMN1 gene is not working properly or is missing and SMN protein cannot be made by the SMN1 gene. This is extremely serious because the SMN1 gene typically makes most of the SMN protein your body needs.

When the SMN1 gene cannot make SMN protein, the body relies on the SMN2 backup genes for this. Unfortunately, the SMN2 gene makes only about 10% of working protein compared to the protein produced by the SMN1 gene. That means that people with fewer SMN2 copies won’t make enough SMN protein. The severity of SMA is related to the number of copies of the SMN2 gene. SMA Type 1 is the most common type of SMA and is very serious. Individuals with SMA Type 1 typically have only two SMN2 backup genes.

Without enough SMN protein, motor neuron cells become weaker and weaker and eventually stop working, lose all function, and die. As a result, muscles can become so weak that eating, breathing, and moving become difficult, and the disease becomes life threatening.

Let’s learn how ZOLGENSMA works to treat SMA. It has two parts⁠—a gene and a vector⁠—and is made in a laboratory by scientists. First, let’s focus on the gene. It’s a new, working copy of a human SMN gene that replaces the function of the nonworking or missing SMN1 gene to restore SMN protein production in the motor neuron cells.

Now, let’s look at the vector. The vector used by ZOLGENSMA is made from a virus called adeno-associated virus 9, or AAV9. This type of virus does not make people sick. To make the vector, the DNA of the virus is removed. With the DNA gone, the fully functional SMN gene is placed inside the vector. The reason why ZOLGENSMA uses vectors to deliver the new genes is because they can travel quickly throughout the body to the motor neuron cells.

But how does ZOLGENSMA work? Once inside the body the vectors deliver new, working copies of SMN genes to the motor neuron cells. ZOLGENSMA sits inside the nucleus of the motor neuron cell and does not become part of the child’s DNA. Then, the new genes tell the motor neuron cells to start making SMN protein. This process happens repeatedly throughout the body with many vectors delivering new SMN genes to motor neuron cells so that SMN protein can be made in those cells.

Once the genes reach their destination, the vectors are broken down and excreted from the body.

ZOLGENSMA—changing the future of SMA treatment.

Close the transcript

Signs and symptoms of SMA may include:

Knowing what signs and symptoms to look for is critical in getting a diagnosis and starting a treatment.

  • A “floppy” baby or hypotonia
  • Small or weak muscles
  • Difficulty breathing/belly breathing
  • Feeding issues, like choking or trouble swallowing
  • Weak sucking and labored breathing during feeding
  • Tongue fluttering
  • Bell-shaped chest (a result of muscle weakness)
  • Weak cough
  • Lack of reflexes
  • “Frog legs” or the inability to kick while lying on back
  • Lack of motor development, like being unable to lift head or roll over
  • Inability to sit
  • Weak cry

If you think your child has any of these symptoms, trust your instinct and immediately contact your doctor for a referral to a pediatric neurologist.

Download Facts About SMA

Does my child have SMA?

Get the Facts About SMA to bring to your child’s doctor to determine next steps.

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Important Safety Information

What is the most important information I should know about ZOLGENSMA?

  • ZOLGENSMA can cause acute serious liver injury. Liver enzymes could become elevated and may reflect acute serious liver injury in children who receive ZOLGENSMA.
  • Patients will receive an oral corticosteroid before and after infusion with ZOLGENSMA and will undergo regular blood tests to monitor liver function.

Important Safety Information

What is the most important information I should know about ZOLGENSMA?

  • ZOLGENSMA can cause acute serious liver injury. Liver enzymes could become elevated and may reflect acute serious liver injury in children who receive ZOLGENSMA.
  • Patients will receive an oral corticosteroid before and after infusion with ZOLGENSMA and will undergo regular blood tests to monitor liver function.
  • Contact the patient’s doctor immediately if the patient’s skin and/or whites of the eyes appear yellowish, or if the patient misses a dose of the corticosteroid or vomits it up.

What should I watch for before and after infusion with ZOLGENSMA?

  • Viral respiratory infections before or after ZOLGENSMA infusion can lead to more serious complications. Contact the patient’s doctor immediately if you see signs of a possible viral respiratory infection such as coughing, wheezing, sneezing, runny nose, sore throat, or fever.
  • Decreased platelet counts could occur following infusion with ZOLGENSMA. Seek immediate medical attention if a patient experiences unexpected bleeding or bruising.

What do I need to know about vaccinations and ZOLGENSMA?

  • Talk with the patient’s doctor to decide if adjustments to the vaccination schedule are needed to accommodate treatment with a corticosteroid.
  • Protection against respiratory syncytial virus (RSV) is recommended.

Do I need to take precautions with the patient’s bodily waste?
Temporarily, small amounts of ZOLGENSMA may be found in the patient’s stool. Use good hand hygiene when coming into direct contact with bodily waste for 1 month after infusion with ZOLGENSMA. Disposable diapers should be sealed in disposable trash bags and thrown out with regular trash.

What are the possible or likely side effects of ZOLGENSMA?
The most common side effects that occurred in patients treated with ZOLGENSMA were elevated liver enzymes and vomiting.

Indication

What is ZOLGENSMA?
ZOLGENSMA is a prescription gene therapy used to treat children less than 2 years old with spinal muscular atrophy (SMA). ZOLGENSMA is given as a one-time infusion into the vein. ZOLGENSMA was not evaluated in patients with advanced SMA.

The safety information provided here is not comprehensive. Talk to the patient’s doctor about any side effects that bother the patient or that don’t go away.

You are encouraged to report suspected side effects by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch, or AveXis at 833-828-3947.

Please see the Full Prescribing Information.

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