Research, treatment benefit from NIH grant and network
Research, treatment benefit from NIH grant and network
Rett syndrome research offers good example
Many patients and families coping with a rare disease are offered some hope in the long term because of the research generated in the Rare Diseases Clinical Research Network (RDCRN), which was launched in 2002 by the National Institutes of Health (NIH) and $71 million in funding awards.
One rare disease called Rett syndrome is believed to affect between 5,000 and 20,000 girls in the United States. The NIH-funded research that is underway holds hope for both greater understanding of the disease process and potential treatments down the road.
Investigators studying the disease describe its impact on patients and how their research might improve the lives of patients and families:
• Characterizing Rett syndrome: Rett syndrome is a neurodevelopment disorder that predominantly affects females, says Steve Skinner, MD, a senior clinical geneticist and associate director of the Greenwood Genetic Center in Greenwood, SC. Skinner also is the director of clinical services, and studies Rett syndrome and Angelman's syndrome.
"Basically, these girls are normal at birth and have a period of normal development for the first six to 18 months of life, and then they start to have regression and lose skills they did have," he explains. "Then there's a period of stabilization, and most of these girls have no or very little verbal communication or speech."
Boys born with the syndrome typically have a more severe form of it and do not survive into the second year of life, says Alan K. Percy, MD, professor in pediatrics, neurology, neurobiology, and genetics, and associate director of the Civitan International Research Center at the University of Alabama at Birmingham. In 1983, Percy was one of the first physicians in the United States to recognize Rett syndrome.
People with Rett syndrome communicate through eye gazing, and they have significant motor and balance problems. One characteristic of the syndrome is stereotypic hand mannerisms in which the girls engage in repetitive activities such as ringing, clapping, posturing, Skinner says.
"They have a fairly normal lifespan, but frequently have feeding and growth issues," he says. "Many are small in stature, with small heads, small hands and feet."
From age four to eight years, the girls will become more attentive and interactive and may be able to use special communication techniques, such as using computer switches to indicate choices, Percy says.
• How it can be treated currently: There is no treatment for those afflicted, but recent research in the United Kingdom has shown that, in mice, it is possible to correct the genetic defect, even late in the disease process, causing a reversal of genetic problems, Skinner says.
"That gives hope to families," he says. "Previously with neurological disorders we felt you had to intervene and treat early before you lost development during the critical periods of development."
• Research to achieve better understanding of disease: The Rett syndrome group has enrolled 500 patients at three institutions, and the goal is to enroll 1,000 patients in a natural history study, Skinner says.
"To do that, we've teamed up with the Universal Rett Syndrome Association," he adds.
Since Rett syndrome has not been long recognized, its long-term course and predicted survival have yet to be studied, and that's what the natural history study will accomplish, Percy says.
"We're in the process right now of wrapping up data entry for survival studies so we can give information to families of what they can expect in terms of longevity," Percy explains. "That has major implications for long-term therapeutic interventions."
For instance, if Rett syndrome is a short-term disorder, then public schools might not be interested in assisting families with educating these patients. But if it's a long-term disorder, then the schools might provide long-term interventions, Percy explains.
• Other goals of research into Rett syndrome: Research focusing on common mutations in the disease might help explain the relationships between specific individuals and their severity of illness, Percy says.
"We have some idea of which mutation provides more mild involvement and which produces more severe involvement, and this information will guide clinicians in treatment," he says.
Some of the growth data collected in the research will lead to the development of growth charts, Percy says.
"The model we're using could be adapted to develop similar growth curves for other disorders, such as for Down's syndrome, for example," Percy says. "It does help to know where a child with a given disorder fits in with the general disorder in the population."
Also, girls with Rett syndrome have a higher rate of fracture, and their bones are very thin, Percy notes.
"One investigator is actively pursuing this and is finding that treatment giving more calcium by mouth could be generalized to other disorders," Percy says.
For example, many girls with Rett syndrome have surgery for scoliosis, so this research could provide some outcomes for a range of disorders, he adds.
"And then because some of the work emerging out of the laboratory with animal models suggests that certain behaviors associated with Rett syndrome could be treated with existing medications, these girls are very anxious and fearful, and we're looking at the possibility of treating them with anti-anxiety medications to see if these improve their behavior and their ability to interact with other individuals," Percy says.
• A quality of life measurement as substudy: "A quality-of-life measurement for Rett syndrome families hasn't been done on any large level in the United States, but we're assessing and measuring the quality of life of caregivers and caregivers' perceptions of quality of life for their daughter," says Jane Lane, RN, BSN, a research nurse manager at Civitan International Research Center. Lane works with Percy in the study of Rett syndrome.
"There are no measurements or tools specific for Rett syndrome, so we piloted a general childhood health questionnaire about diseases for children and applied these to our group of girls and women," Lane says.
"We think that will have interesting data," Lane notes. "We've spearheaded that substudy, also."
Since there had been no previous measurement of life quality for Rett syndrome, investigators worried that girls with the disease would bottom out on some of the questions, Lane says.
But the pilot study showed that the questionnaire could be used and answers would vary enough to be informative, she adds.
Many patients and families coping with a rare disease are offered some hope in the long term because of the research generated in the Rare Diseases Clinical Research Network (RDCRN), which was launched in 2002 by the National Institutes of Health (NIH) and $71 million in funding awards.Subscribe Now for Access
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