Kids With Spinal Muscular Atrophy Show Dramatic Improvement With FDA-Approved Gene Therapy

Waking up, hopping out of the bed, and stumbling to the kitchen for a cup of coffee: It’s an everyday routine most people don’t think twice about.

But for children with spinal muscular atrophy, simply propping themselves up in bed is an everyday struggle. The inherited disease is caused by mutations in the SMN1 gene. Without a working copy of the gene, motor neurons—cells that control muscles—rapidly wither.

Symptoms occur early in life. In the most severe cases, six-month-old babies can’t sit up without help. Others struggle to crawl or walk. The disease doesn’t affect learning and other cognitive abilities. Babies with the condition soak in their surroundings, and their brains develop normally. All the while, the disease cruelly destroys their bodies.

Left untreated, muscle weakness expands to the lungs, potentially causing deadly breathing problems. If there’s a silver lining, it’s that the disease has a clear genetic foe to target. Thanks to gene therapy, three treatments, approved by the FDA, can halt the disease in its tracks—if a patient is under two years old.

There’s a reason for the age limit. After two, the disease has already damaged motor neurons to such a degree that the therapy is no longer helpful.

Not so fast, two international teams of physicians and scientists wrote in December.

The teams published highly promising results from separate trials testing an experimental gene therapy, called Itvisma, in kids between 2 and 18 years of age. The new therapy is based on a previously approved version made by the drug company Novartis. Both have the same gene-correcting ingredient but are administered differently. The original relies on a shot into the bloodstream. Itvisma is delivered directly into the spinal cord.

The two recent trials brought significant improvement in participants’ ability to move over the course of a year. From not being able to walk, treated kids were able to roll into a sitting position from lying down and climb stairs, compared to children who did not receive treatment.

The results “demonstrate clinical benefits across a broad…population with a wide range of ages and baseline motor functions,” wrote Richard Finkel at St. Jude Children’s Research Hospital and team, on behalf of a broader STEER Study Group that conducted one of the trials.

The FDA agreed. In late November, the agency approved Itvisma for the disease, making it the only gene replacement therapy for people two years and older on the market.

“This achievement is not only a significant step forward for SMA [spinal muscular atrophy]–it also signals new possibilities for the broader field of neurological disorders and genetic medicine,” said John Day at the Stanford University School of Medicine in a Novartis press release.

Transformative Shot

Like its predecessor, Itvisma uses a harmless virus to carry a healthy version of the SMN1 gene into the body. The virus shuttles its cargo into cells but doesn’t tunnel into the genome. This makes it relatively safe, as it doesn’t raise the risk of unintended vandalism to the cell’s native DNA.

The previous therapy was a one-and-done shot into the bloodstream. The virus hitched a ride to motor neurons and restored their connection to muscle fibers. The liver and heart also received an unintentional dose, which could potentially cause side effects. Researchers carefully monitored children given the therapy for liver problems. These were relatively mild and easily treated.

The results were dramatic. Most treated infants were able to sit up, roll around in their cribs, and some could even crawl. But the treatment was only approved for children aged two years or younger.

Two problems hampered its broader use. One was timing: The disease rapidly eats away at motor neurons, causing long-term damage that’s difficult to restore. The other was safety. Gene therapies injected into blood are tailored to the recipient’s body weight—the higher the weight, the larger the required dose. Higher doses raise the risk of dangerous side effects, potentially causing the immune system to hyperactivate or cause damage to the liver.

For a toddler or teenager, the risk-benefit calculation didn’t work in the gene therapy’s favor.