Hope for girls with autismlike disease

WASHINGTON — Scientists are raising the first hope of recovery from an autismlike disease that leaves thousands of girls unable to talk or walk, with an experiment that erased symptoms of the disorder in genetically engineered mice.

Thursday's report challenges the long-held belief that the brain damage from Rett syndrome is permanent, but it comes with a big warning: Researchers don't know how to even try such treatment in people yet, making the discovery one of both optimism and continued frustration.

"The thing that keeps your feet on the ground with this study is it shows the principle of reversibility, but doesn't give you any clue about how to accomplish that," cautioned lead researcher Dr. Adrian Bird, a geneticist at Scotland's Edinburgh University.

Still, parents rejoiced at the research, saying it gave them hope that even if finding actual therapies takes another decade, their daughters still may have a chance to improve.

"To think even 10 or 20 years down the road ... she could learn to talk and walk," said Jennifer Endres of her daughter Jillian, 4.

And the work, published Thursday by the journal Science, could affect more than Rett syndrome, because the same genetic culprit plays a role in certain forms of autism and other brain diseases, too.

"In this class of disorders, now we have a great hope that if we figure out a way to manipulate the function of the neurons ... we have a chance of recovery," said Dr. Huda Zoghbi of the Baylor College of Medicine. Zoghbi discovered Rett's genetic culprit in 1999.

Rett syndrome is rare, afflicting roughly one in 10,000 girls. (Boys who are stricken almost always die in infancy.)

But Rett is the most physically disabling of the family of autism diseases. Girls are born healthy but then the culprit gene somehow mutates, destroying speech and normal movement. A classic sign is hands that can do nothing but wring. Many children never walk; those that do have a stiff-legged gait. Symptoms usually appear between 6 and 18 months of age. Patients can live to adulthood, although many die of infections before then.

What goes awry: a gene called MECP2 that is supposed to switch off other genes involved in the maturation of neurons. When MECP2 shuts off in Rett syndrome, girls' brain cells don't die, but they don't keep developing.

The question is whether switching that gene back on could restore neuronal function. Even Bird didn't think so — he was stunned by his own team's finding.

The experiments couldn't test cognitive functions, such as speech, just physical ones.

But "the work is really beautiful," said Dr. Uta Francke of Stanford University, a co-discoverer of MECP2 gene who has studied and cared for Rett patients for 20 years. "They have very convincing evidence" that damage once thought permanent is reversible.