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 1 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.
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