In 2013, Zoe Harting became the first baby in the world to receive an experimental drug that her doctors hoped would save the lives of thousands of infants like her.

Zoe has spinal muscular atrophy type 1, a degenerative neuromuscular disease that kills most patients by their second birthday.

Before she began receiving the drug, 7-month-old Zoe was quite weak. She couldn’t sit up or roll over. She couldn’t move her legs at all, or lift her arms when she was lying down. She struggled to swallow. Her parents, John and Eliza Harting, knew that without an effective treatment, she would soon struggle to breathe. But no treatment had ever succeeded against SMA-1. So when the Hartings got a call from Stanford pediatric neurologist John Day, MD, PhD, asking if they would consider enrolling Zoe in a phase-2 clinical trial of an experimental drug called nusinersen, they agreed.

“I’ve seen so many kids die with this disease,” said Day, who directs the Neuromuscular Disorders Clinic at Lucile Packard Children’s Hospital Stanford and is a professor of neurology and of pediatrics at the Stanford University School of Medicine.

SMA-1 is the most common genetic cause of death in infants. It’s triggered by a gene mutation that is carried by 1 in 40 people. The disease, which occurs when a child inherits the mutated gene from both parents, is diagnosed in about 250 babies per year nationwide. In the past, pediatric neurologists could help make patients comfortable as their health declined, but that was all. “We would have to tell the parents, ‘I’m sorry, we don’t have anything that will stop the progression of the disease,’” Day said.

The drug nusinersen is changing that.

Improvement in meeting motor milestones

On Dec. 6, the results of the phase-2 trial that Zoe Harting helped to launch were published in The Lancet. Day is a co-author of the study, which was led by pediatric neurologist Richard Finkel, MD, of Nemours Children’s Hospital in Orlando, Florida. Nusinersen is safe and well-tolerated, the study reports. Although the multisite trial included only 20 children and was intended primarily as a safety test, the investigators report significant improvements in patients’ ability to achieve motor milestones, as well as better motor function and increased function of nerves that are attacked by the disease.

The drug is quickly progressing through the regulatory approval process. In addition to the phase-2 trial in which Zoe participated, nusinersen has been evaluated in a phase-3 trial of SMA-1 patients, which was stopped early in August because it was obvious that infants receiving the drug were achieving significantly more motor milestones than those in the control group. The phase-3 trial is now an open-label study, meaning that all participants can receive nusinersen.

The drug is expected to receive approval from the FDA within the next two months, and in the interim is available under an expanded access program at a few sites around the country, including Lucile Packard Children’s Hospital Stanford.

“This drug completely turns things around for SMA,” Day said. “It’s a definite game-changer.” An even larger discovery is that drugs with the same mechanism of action may help treat other genetic diseases, he added. Nusinersen is an antisense oligonucleotide, which works by sticking to a specific piece of genetic material. Trials of antisense oligonucleotide drugs are now underway for other neurological diseases, including myotonic dystrophy, Huntington’s disease and amyotrophic lateral sclerosis.