Article 1/5

Gene Therapy Makes Promising Headway Against SMA1

Researchers from Nationwide Children’s and The Ohio State University published astonishing results of the phase 1 clinical trial of gene therapy for spinal muscular atrophy type 1 (SMA1) in the November 2017 edition of the New England Journal of Medicine.

“All in all, it’s one of the most successful gene therapy trials,” says Jerry Mendell, MD, principal investigator in the Center for Gene Therapy and research leader. “Not all of them can show they save lives.”

It’s the kind of result Dr. Mendell began pursuing as a resident and fellow at the National Institutes of Health in the early 1970s.

The SMA1 trial demonstrated extended survival and increased achievement of milestones previously unseen in the natural course of the disease, which typically results in death by age 2. An intravenous injection of AVXS-101, a modified adeno-associated virus serotype 9 (AAV9), delivered the survival of motor neuron (SMN) gene to 15 patients.

Three patients received a low dose; 12 received a high dose. All patients appeared to have a favorable safety profile and the therapy was generally well tolerated. Of high-dose patients, 92 percent achieved head control, 75 percent rolled over and 75 percent sat for 30 seconds or longer as of the August 2017 data cutoff. Two patients could crawl, pull to stand and walk independently.

According to its natural history, SMA1 patients require nutritional and respiratory support by one year and are unable to swallow or speak effectively. Among the high-dose patients, 11 spoke, 11 fed orally and seven did not require bi-level positive airway pressure.

Dr. Mendell, recognized as the first person to study viral-mediated gene therapy for muscular dystrophy in humans, has also studied SMA for decades. He credits colleagues at The Ohio State University and AVXS-101 developer AveXis for efforts and discoveries that were essential to the study’s success.

The research was named Science Breakthrough of the Year in the People’s Choice category. The trial was one of two that received the Clinical Research Forum’s Distinguished Clinical Research Achievement Award.

Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L'Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single-dose gene-replacement therapy for spinal muscular atrophy. New England Journal of Medicine. 2017 Nov 2;377(18):1713-1722.

Behind the Breakthrough

  • The trial builds on nearly 30 years of foundational research and collaboration.
  • Multidisciplinary teams from Nationwide Children’s collaborated with Ohio State’s Wexner Medical Center as a result of strong basic science and clinical connections between the two institutions.
  • In 2014, Nationwide Children’s enrolled the first infant ever treated with gene replacement therapy for spinal muscular atrophy.
  • Preliminary results of the phase 1 study announced in 2017 mark a significant milestone in the advancement of therapies that may ultimately alter the course of spinal muscular atrophy type 1.
Previous Article
Our Milestones
Next Article
Cannabidiol Significantly Reduces Seizures in Hard-To-Treat Syndrome