BY SARAH OWENS
Children with spinal muscular atrophy (SMA) were found to benefit from a single infusion of a gene therapy to replace a defective gene known to cause the progressive, life-threatening disease.
More than three years later, the children who received the gene therapy have survived longer, had superior results on motor milestones, and achieved better motor function than children who did not have the therapy, according to the study published in the November 2 issue of The New England Journal of Medicine.
A Dire Need for Treatments
SMA is caused by a defect in the spinal motor motor 1 (SMN1) gene, which is responsible for the creation of SMN, a protein that helps ensure the survival of motor neurons that control voluntary muscle movement. The defect causes infants with SMA to experience progressive muscle wasting, and without treatment they die or need permanent breathing (ventilation) support by age 2.
Testing Gene Therapy
In the current study, researchers packed the healthy SMN1 gene into a virus modfied so that it wouldn't cause illness. Because scientists can't insert the gene directly into the cell, they use the virus, or vector, to target the cell, enabling it to pump out a healthy supply of SMN1 that is crucial for motor development.
The researchers gave three boys a low dose of the gene therapy between May and September 2014 and gave 12 boys a high dose between December 2014 and December 2015. The researchers followed the patients up until August 2017 to determine their outcomes.
When the study ended, all of the boys were still surviving, and none of them required permanent breathing support – a major achievement, given that previous research shows only 8 percent of patients with SMA will survive untreated. Their scores on a scale of motor function called CHOP INTEND – which measures muscle tone, reflexes, and posture, as well as the ability to kick, crawl, stand, speak, pay attention, and more – also rapidly increased, especially in the high-dose group.
Even more encouragingly, the boys were found to achieve what the researchers called "motor milestones": 11 were able to sit unassisted for at least 10 seconds, and nine could sit for 30 seconds; 11 were able to control their heads; nine could roll over; 11 were fed orally and were able to speak; and two could crawl, pull themselves up, stand independently, and walk independently. Side effects of the therapy were generally mild.
Hope on the Horizon
The findings, the study authors say, raise the possibility that gene therapy could be a promising treatment to help children with SMA survive and develop their motor function over the long term. However, they note that the long-term effects of the therapy are still unknown; they will continue to monitor the children through at least age 15 and report their findings, they add.