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Epilepsy Drug Shows Promise in Treating Spinal Muscular Atrophy

October 18, 2007

Joseph Miller, 4, demonstrates a feat of flexibility for physical therapist Jill Hartman.

Tell 4-year-old Joseph Miller he’s cute, and he’ll correct you. “No. I’m ruggedly handsome,” he will say impishly. With his mop of brown hair, infectious grin and precocious ease among adults, he really is.  In the pediatric clinical research unit (PCRU) at the Children’s Center, physical therapist Jill Hartman walks him through tasks, from stretching a gummy worm to pointing his toes, designed to measure his muscle strength. Joseph has spinal muscular atrophy (SMA) and is participating in a clinical study of a potential new treatment to stem or reverse the muscle weakness that makes it difficult for him to sit upright and nearly impossible to button his shirt, and that threatens to worsen.

Affecting one in 6,000 newborns, SMA is the leading genetic killer of children under 2 years old. A neuromuscular disease with no cure, it’s severity differs in individuals. One variety kills in infancy; the other strikes in varying degrees at varying ages. Children are most often diagnosed when growth and mobility hallmarks aren’t met, ranging from a few weeks to 2 years, while those mildly affected can go undiagnosed for years.

“In my clinic, I have babies who die young, children in motorized wheelchairs and young adults whose only problems are that they can’t bound up stairs,” says Children’s Center pediatric neurologist Tom Crawford, an SMA expert and a lead researcher of a multisite study of the effectiveness of the FDA-approved epilepsy drug valproic acid (Depakote) in stopping or slowing the disease’s progressive muscle atrophy. He has enrolled 15 patients in Hopkins’ participation in a six-site study of more than 90 children.

SMA looks something like polio. It damages the motor neurons, weakening muscles. Affected children tend to be hyperflexible, given their relatively weak muscles. They’re helped by firm vests that keep their spine straight to avoid scoliosis and therapy intended to clear their lungs, since coughing is difficult.

“We think that the drug can make the neurons work better by increasing a particular protein,” says Crawford. “What does not make these kids stronger may still reduce their deterioration.”  “This is a beautifully run study,” says Tim Reilly, a research scientist, whose nearly 2-year-old son, Matthew, was diagnosed at 13 months in their hometown of Syracuse, N.Y. He and his wife met Crawford at an SMA conference in Philadelphia soon after.  “While all the researchers were sitting in their own corner, Crawford sat with the families,” says Miller. “He even gave our son a quick exam. He’s wonderful.”

Like Joseph, Matthew comes to the Children’s Center every three months for a two-night stay and a medical evaluation by Crawford, which includes a blood test designed to determine whether the drug is increasing a protein that protects against neuron damage. Their range of motion is measured and videotaped.

Crawford expects to have preliminary results by early 2008. Early indications suggest that the study will be successful.