Providing Hope for Infants With Spinal Muscular Atrophy

A single infusion of a new treatment called Zolgensma (onasemnogene abeparvovec) can prevent the severe neuromuscular effects of spinal muscular atrophy (SMA), a genetic condition associated with serious neuromuscular dysfunction and high mortality.

In a clinical trial involving infants with the most severe form of SMA, 97% of participants who received the treatment were able to breathe without permanent respiratory support by fourteen months of age, whereas only 26% of patients in a previous study of untreated infants could do so. Additionally, while none of the untreated infants could sit independently by eighteen months, 44% of the infants treated in the clinical trial achieved this milestone.

“This is the first neuromuscular condition that has been successfully treated with genetic therapy,” says Vettaikorumakankav “Veda” Vedanarayanan, MD, FRCPC, a board-certified pediatric neurologist in UT Health Austin Pediatric Neurosciences at Dell Children’s, a clinical partnership between UT Health Austin and Dell Children’s Medical Center. “So far, six children have undergone Zolgensma treatment at Dell Children’s.”

What is SMA?

SMA is caused by a mutation in a single gene known as the SMN1 gene. In healthy individuals, this gene provides the code for the survival motor neuron (SMN) protein, which is present in almost all tissue and allows for cell survival. In patients with SMA, deficiencies in this protein lead to loss of the motor neurons in the spinal cord, impacting the instructions the body can receive from the brain about voluntary movement. When left untreated, children born with the most severe form of SMA typically do not survive past the age of two, while those with other forms of SMA face lifelong motor challenges.

How is SMA diagnosed?

As of July 2021, all newborns in the state of Texas are screened for SMA, but babies can be tested before they are even born. Testing for the condition as soon as possible gives parents an advantage in deciding how and when to proceed with treatments like Zolgensma.

“Prenatal genetic testing has advanced a lot over the past twenty years,” says Amy Young, MD, a board-certified obstetrician-gynecologist in Women’s Health, a clinical partnership between UT Health Austin and Ascension Seton. Dr. Young also serves as the Chief Clinical Officer for UT Health Austin.

Dr. Young recommends that couples hoping to start a family undergo counseling even earlier, a few months before they plan to conceive, to determine whether they are a carrier for mutations that cause genetic conditions like SMA through blood testing and discuss their risk of having a child with such conditions. “Pre-conceptual counseling can help optimize outcomes for the baby,” says Dr. Young. “In addition to discussing genetic conditions, pre-conceptual counseling covers a variety of topics, including proper nutrition and any occupational hazards that may put the baby at risk.”

Learn more about Prenatal and Preconceptional Genetic Counseling services available through Women’s Health.

How does Zolgensma work?

Zolgensma is a gene therapy, meaning it uses genetic material to correct a genetic mutation. In Zolgensma, the SMN1 gene is packaged inside a safe virus called adeno-associated virus 9 (AAV9), which helps the gene enter the spinal motor neurons and reach the nucleus of the cell. This delivers a working copy of the SMN1 gene to the motor neurons, allowing them access to the genetic instructions for producing the SMN protein they need to function.

“The neat thing is that the copy of the SMN1 gene will not integrate with the rest of the host cell’s genetic information but will, instead, act as a separate system that keeps producing the SMN protein,” says Dr. Vedanarayanan. By keeping the SMN1 DNA separate, this treatment avoids negative health outcomes resulting from errors that could occur when a new gene is directly inserted into a host cell’s genetic code.

What can families expect during treatment?

Following a formal diagnosis of SMA, Dr. Vedanarayanan recommends the patient undergo treatment as soon as possible to experience the best outcome. The procedure is typically performed within the first few weeks of life.

“The babies who receive gene therapy are carefully screened for liver function and heart function. They also undergo viral antibody screening to understand how the baby’s immune system may react to AAV9, the vessel that carries the SMN1 gene into cells,” explains Dr. Vedanarayanan.

The day before treatment, the patient is given a course of steroids to help regulate their liver’s immune response to AAV9. When the patient arrives at the hospital for the procedure, they are given an intravenous infusion of the medication over the course of an hour.

Patients are usually free to return home the day after the infusion but will need to be brought in for weekly follow-up appointments over the course of the next month so that continued steroid dosing can be monitored and lowered. During follow-up visits, the patient’s heart and liver function will also be evaluated.

Are there any side effects associated with Zolgensma?

“The short-term side effects associated with Zolgensma are similar to that of the flu,” says Dr. Vedanarayanan. “For this reason, the child is monitored at the hospital overnight to ensure proper hydration if they begin to experience vomiting or diarrhea. Other common side effects are lethargy and fever.”

In rare cases, serious long-term side effects, such as liver failure, have been detected during follow-up visits. Parents considering this treatment should consult with a physician to better understand the risks and benefits of Zolgensma.

Is there anyone who shouldn’t undergo treatment?

“Children with an immune sensitivity to AAV9 should not undergo Zolgensma treatment,” shares Dr. Vedanarayanan. Once a child is identified as having SMA, they are tested for this immune sensitivity. Patients who test positive can be given other SMA treatments until the sensitivity resolves itself, at which point they can be considered for Zolgensma again.

To learn more about this treatment from a family’s perspective, read CBS Austin’s coverage of a patient recently treated for SMA at UT Health Austin Pediatric Neurosciences at Dell Children’s.

<br>For more information about UT Health Austin Pediatric Neurosciences at Dell Children’s or to request an appointment, visit here.

To learn more about Women’s Health or request an appointment, visit here.