Gene therapy trial treats infant paralysing disorder

Gene therapy for a fatal inherited paralysing disease called spinal muscular atrophy, SMA, that strikes in infancy has been successfully tested by scientists in the US.

About 1 baby in every 11,000 is affected by SMA, which leads to a progressive paralysis caused by the relentless destruction of the spinal motor nerves that instruct muscles to make movements. The condition is life-limiting and the majority of infants who inherit the disease do not survive beyond the age of 18 months.

The gene linked to SMA is carried on Chromosome 5 and called SMN-1, which stands for "survival motorneurone". Scientists don't know for sure what it does or how this gene contributes to keeping motor nerves healthy, but without it the cells suffer biochemical stress and die off.

Luckily there is a second gene, called SMN-2, which does much the same job as SMN-1 although it is present at much lower levels. Efforts have therefore focused on trying to increase the activity of this gene, and specifically a region of the gene, called exon 7, which is frequently "skipped over" when cells read the SMN-2 gene.

Including this "skipped" section can enable SMN-2 to replace the role of the missing SMN-1. To make this happen, a team led by Richard Finkel at Nemours Children's Hospital in Florida have developed a genetic sticking plaster that can access motor nerve cells and instruct the genetic machinery of the cells to use the SMN-2 gene and to include the critical exon-7 message.

Their therapy, which is called "Nusinersen" has now progressed through a phase 2 clinical trial and the results from the 20 infants that received the therapy are announced this week in the medical journal The Lancet.

The affected children were enrolled in the trial, on average, 140 days after they were born. The therapeutic genetic message was injected via a lumbar puncture procedure into the fluid around the spinal cord. After a sequence of "loading" doses the children then received a top-up maintenance injection every 4 months. They were followed up regularly and the team made measurements of their kicking, grasping, sitting, walking and head control abilities.

Over the following two years, sixteen of the participants have achieved improvements in their motor function; some individuals could even sit independently or roll over and were able to stand and walk, changes that are, as the researchers highlight in their Lancet paper, "beyond the motor repertoire expected for infants with spinal muscular atrophy."

On the basis of this success, the investigations have now progressed to a phase 3 trial...