Tests aim to solve genetic mysteries

Colin English at 3 1/2 months is a normal, healthy baby boy. The only hint of what his future may hold is the tube that runs into his nose and down through his stomach to make giving him medicine easier.

His parents, Monica and John English, know that, unlike his sister Taleah, he will one day sit up and may even walk.

Taleah, 3, reclines on a special stroller, always flat because she cannot swallow easily. Her hold on life is fragile, but she is vibrant and, though physically restricted, very active.

The difference between the two is the number of copies of a gene called SMN2 (survival motor neuron 2), a protein that helps motor neurons survive, as the name implies, says Dr. Kathryn Swoboda, a neurologist, geneticist and researcher at Primary Children's Medical Center. She is conducting clinical trials in hopes of changing the future of children like Taleah and Colin, who were born with spinal muscular atrophy.

SMA, its common shorthand name, is a recessive disorder; both parents have a specific gene deletion that causes the disease. But since one in 40 are carriers, it's not that uncommon. The chance of a child having SMA in those families is one in four; Taleah and Colin have older siblings who don't have the disorder.

The diagnosis, years ago, was without hope: muscle weakness and atrophy, inability to swallow, death. These days, the National Institutes of Health believes the odds of a cure or at least drastic improvement are so high that it has provided funding as a transitional research project.

Swoboda is using drugs to manipulate the SMN2 copies that determine how well children with SMA do. Sodium phenylbutyrate, used for years in newborns with other disorders, is known to be safe. The question is, is it effective with SMA? There are concerns about using another drug, valproic acid, in newborns. But it holds great promise. Valproic acid also is used for other conditions, such as seizure control in people with epilepsy or as a mood stabilizer in folks with Alzheimer's.

Both drugs were picked up as a possible SMA treatment on a drug screening survey. They work by the same general mechanism. They open up the DNA and allow genes that normally are not expressed to be expressed at a higher level.

Animal research indicates the drugs may "rescue the picture" in mice with SMA. It's just one approach. Other work shows that infusing stem cells into rats who are paralyzed gives them the ability to walk. But it's early work. And it's hard to get stem cells into the nervous system. With SMA, muscular symptoms are actually secondary to devastating nerve deficits.