Identifying the first young girl with Rett syndrome in the Houston community many years ago redirected Alan Percy’s career path from a basic science laboratory to the recruitment of several key figures into Rett syndrome research.
Percy, professor of pediatric neurology and medical director of the Civitan International Research Center, has been involved with Rett syndrome since it was first identified in the United States and now is a highly recognized an authority on Rett syndrome and other rare neuro-developmental diseases.
Alan Percy (top) discusses Rett syndrome research strategy with Stacey Watkins in his lab. Percy recently was honored by the International Rett Syndrome Foundation with The Art of Caring Award — the highest honor given to a clinician from the Foundation.
The International Rett Syndrome Foundation recently honored Percy with its highest award for a clinician, naming him the recipient of The Art of Caring Award. Clifford and Judy Fry — one of his first patient families — presented the award to Percy at the IRSF’s 25th annual Family Education and Information Conference during the Memorial Day weekend.
Percy has been responsible for recruiting researchers — including the internationally renowned Huda Zoghbi, M.D., — and the development of a clinical and translational research program that has placed Rett syndrome researchers on the doorstep of direct, effective treatment for this unique neuro-developmental disorder primarily affecting girls and women.
“It has been a privilege to work with a group of dedicated physician-scientists to achieve this goal and to serve the individuals and their families directly affected by it,” Percy says. “The recognition by the IRSF family of our work in service to those affected by Rett syndrome is greatly appreciated, yet quite humbling against the knowledge that we still have far to travel to achieve our goal.”
Rett syndrome (RTT), a brain disorder affecting development in childhood, has been identified almost exclusively in females. RTT results in severe movement and communication problems following apparently normal development for the first six months of life. The characteristic features include loss of speech and purposeful hand use, repetitive hand movements, abnormal walking, abnormal breathing and slowing in the rate of head growth. No cure for Rett syndrome is known.
Percy recently talked with the UAB Reporter about the research UAB is conducting on Rett syndrome and other rare neurodevelopmental diseases, treatment for Rett syndrome and the potential for breakthroughs in the treatment of this and other disorders, including autism and schizophrenia.
Q. How many stages of development does Rett syndrome have?
A. Although staging of Rett syndrome was important in the early years, after gaining more experience and learning how to manage the myriad clinical problems, not the least of which is nutrition, the staging system is not of great relevance at this point. Due to the improvements in medical management, we have changed the clinical landscape of RTT for the better.
What is clear is the temporal profile of RTT: a period of normal early development followed by a plateau and then frank regression of developmental skills with subsequent improvement in communication and socialization skills including piercing eye contact, yet with slowing of motor activities (not another regression) through adulthood.
Q. How far has treatment of Rett syndrome come?
A. I often say that the girls and women we meet today are quite different from those 20-25 years ago, all due to better recognition of clinical problems, improved medical management and enhancement of specific therapies including physical, occupational and communication techniques. As such, we are able to anticipate problems before they are deep-seated and address motor issues before irreversible secondary changes such as contractures occur. The parents also are better informed and represent important partners with us to improve outcomes.
Q. What are the current treatment options, and what is the life expectancy with Rett syndrome?
A. No specific treatment exists for RTT, but multiple medical and surgical issues must be monitored. For these, treatment options are available, although the problems are not necessarily present in everyone with RTT. Nutrition must ensure adequate caloric intake, including gastrostomy feeding when oral intake is problematic.
We have learned from studies in the 1990s that these girls have greater caloric requirements per kilogram body weight than the typically developing child. Improved recognition and management of gastroesophageal reflux, constipation and even gallbladder disease have been pivotal. Seizures require accurate diagnosis and appropriate intervention. Heightened anxiety can be treated.
Scoliosis is a common problem that requires regular monitoring and surgical intervention in about 12 percent when the degree of curvature necessitates intervention.
Q. What is the significance of the grant the Civitan International Research Center received from the Eunice Kennedy Shriver National Institute of Child Health and Human Development?
A. This grant has allowed the CIRC to continue its support of research in intellectual and developmental disabilities through the provision of clinical and laboratory cores that can enhance the research capabilities of investigators in these areas of study. Together with other core service grants at UAB, the infrastructure available to individual investigators and their trainees is extraordinary.
Q. What unique areas of research into Rett syndrome and other neurological disorders are being pursued?
A. Current efforts are ongoing along both clinical and basic research pathways. We believe that one day these will converge as treatment trials come online addressing a fundamental cure. From the clinical perspective, through our Rare Disease grant, we are examining the natural history and phenotype-genotype correlations of RTT in order to be in good position for clinical trials.
At the basic level, research in the Pozzo-Miller and Sweatt laboratories is examining the basic role of the RTT gene in brain function, and a new initiative in collaboration with the Pozzo-Miller, Townes and Strong laboratories, along with major support from core grant noted above, is pursuing the development of pluripotent stem cells from skin fibroblasts expressing specific RTT mutations as another vehicle to evaluate the affect of these mutations on nerve-cell development and interaction and to be used as testbeds for evaluating specific therapies.
Q. Have there been any recent breakthroughs in the treatment of Rett syndrome?
A. The fundamental breakthrough in the past two years was the demonstration in mouse models in the Bird lab in Edinburgh and the Jaenisch lab in Cambridge that the features of RTT could be reversible. While not a strategy useful in humans, this work did provide proof of principle that some features, at least, of RTT in humans could be reversible with the proper, effective and safe intervention.
Q. Why is it believed that Rett syndrome may hold the key to finding better treatments and cures for other neurological disorders, including autism and schizophrenia?
A. The gene associated with RTT also may produce other clinical disorders resembling autism or schizophrenia without specific signs of RTT. We are able to manage these behavioral issues pharmacologically to some extent. More important, perhaps, at the biological level, understanding the role of this gene (MECP2) certainly will provide important insights into these and other behavioral phenotypes. This promises to keep many investigators occupied for some time.
For more information about Rett syndrome research conducted by Percy, visit www.mrrc.uab.edu/PI_percy.htm.