Research helps demystify a genetic disorder
♫ Sunday, February 19th, 2012
Dr. Elizabeth Berry-Kravis has spent much of her career focused on Fragile X, a genetic condition involving a mutation on the X chromosome that causes cognitive disabilities, behavioral issues and other problems.
New medications and therapeutic interventions have revolutionized life for people with the syndrome over the past 20 years, but Berry-Kravis, who runs the Fragile X Clinic and Research Program at Rush University in Chicago, said the most exciting discoveries are being explored now.
She was in Houston recently for a meeting of the Fragile X Clinical and Research Consortium at Texas Children's Hospital and spoke with Chronicle reporter Jeannie Kever.
Q. Tell me a little about Fragile X. How many people does it affect, and how does it manifest?
A. The description everyone uses is, it's the most common inherited form of intellectual disability. It's also the most common known genetic cause of autism. Children will seem pretty normal as young babies, but then they'll present to their pediatrician with a delay in walking or acquiring other motor milestones. A delay in talking is common. They'll have ongoing learning difficulties.
In elementary school, most of the guys with Fragile X will be in special education and have occupational therapy, speech therapy. Fragile X patients have a lot of behavioral difficulties, hyperactivity, problems paying attention, sometimes more aggressive behaviors.
It occurs in about 1 in 4,000 people. The gene that causes Fragile X is on the X chromosome. Men have only one copy of the X chromosome; girls have two. In girls, the normal gene on the other X chromosome tends to make the condition milder.
Q. What are researchers looking at?
A. The research that is particularly exciting, we have a mouse that has Fragile X. The mouse brain looks very similar to the human brain (of someone with Fragile X), so we can study the mechanisms of disease in the mouse.
Now we are working on treatments to target those pathways … to try to improve the brain cell connections. We can show that certain agents actually work in the mouse to impact different behaviors.
Some of those are being translated into humans. Now, if a patient has attention problems, we would treat it with medicine. But these new medications are targeted to the actual (behavior-causing) mechanisms.
Q. Is that a new approach?
A. It hasn't been done before in a developmental disorder, so Fragile X has become very hot in the research world. What's happening here will become a model for developing treatments for Down syndrome and autism.
Currently, three drugs are in clinical trials. We don't know really how well the drugs are going to work in people yet. We're very hopeful, but we have to remind ourselves the human is not the mouse.
If these drugs do produce improvements, and particularly if they produce cognitive improvements, which has never been done, it would be pretty earth-shaking.
Q. What does that mean for people with Fragile X and their families?
A. In the past, patients with Fragile X were very difficult. They couldn't be handled in the schools. There weren't good medications to help with their symptoms. They would be excluded from society.
They also tended to acquire very few academic skills, because people believed they weren't teachable. Now we've seen a revolution in teaching these patients. Even without the new drugs, the advances in the past 10 or 20 years about early intervention, molding education to the child … has made a big improvement.
With the advance of behavioral drugs, we can manage the behavior with medications and therapy and educational strategies. More of my patients now are getting out of high school and getting into a job.
If we could treat the biology at least a little bit with these new medications, we would see an added bonus.
jeannie.kever@chron.com
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Research helps demystify a genetic disorder