Baby gene therapy study offers hope for fatal muscle disease

WASHINGTON -- A first attempt at gene therapy for a disease that leaves babies unable to move, swallow and, eventually, breathe has extended the tots' lives, and some began to roll over, sit and stand on their own, researchers reported Wednesday.

Only 15 babies with spinal muscular atrophy received the experimental gene therapy, but researchers in Ohio credited the preliminary and promising results to replacing the infants' defective gene early -- in the first few months of life, before the neuromuscular disease destroyed too many key nerve cells.

"They all should have died by now," said Dr. Jerry Mendell of Nationwide Children's Hospital, who led the work published by The New England Journal of Medicine. Yet, "those babies are still improving."

Mendell cautioned much more study is needed to prove the gene therapy works and is safe. Nor is it clear whether the replacement gene's effects would wane over time.

Spinal muscular atrophy occurs in about 1 in 10,000 births, and those with the most severe form, called SMA Type 1, rarely reach their second birthday. They can be born looking healthy but rapidly decline. One study found just 8 percent of the most severely affected survived to age 20 months without needing permanent mechanical ventilation to breathe.

There is no cure. The first treatment wasn't approved until last December -- a drug named Spinraza that requires spinal injections every few months.

The experimental gene therapy approach aims for a one-time fix.

Spinal muscular atrophy is caused when a mutated gene can't produce a protein crucial for survival of motor neurons, nerve cells in the spinal cord that control muscles.

Some children carry extra copies of a backup gene that produces small amounts of the vital protein, and thus have much milder forms of the disease.

Scientists loaded a healthy version of the gene into a virus modified so it couldn't cause illness. Then 15 babies got a one-time intravenous injection. The virus carried the healthy gene into motor neurons, where it got to work producing the protein those nerve cells require to live.

Three babies received a low dose of the gene therapy, as a first-step safety precaution. The remaining 12 got a high dose.

All of the children are alive, Mendell said, about two years and counting after treatment. All beat the odds of needing permanent machine help to breathe by age 20 months.

But only the high-dose recipients saw better motor control, reaching some developmental milestones usually unthinkable for these patients. Eleven could sit unassisted at least briefly; nine could roll over. Eleven are speaking and able to swallow. Two were able to crawl, stand and then walk, Mendell's team reported.

Those results are "very striking," said Dr. Basil Darras, who directs Boston Children's Hospital's neuromuscular center and wasn't involved in the new research.

While the treatment needs testing on far more babies, usually "there are no further developmental gains" after diagnosis, Darras explained. "They stagnate for a while and they go downhill very fast and die."

The only serious side effect attributed to the gene therapy so far involved possible signs of a liver problem that eased with treatment.

AveXis Inc., which is developing the gene therapy and helped fund Wednesday's study, has opened a second small trial at seven hospitals.