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Percy Headshot MediumAlan Percy, M.D., professor of pediatric neurology, Sarah Katherine Bateh Endowed Professor and CCTS Senior Scientist, was one of the first physicians in the country to diagnose a patient with Rett Syndrome, which affects 1 in every 10,000 female births worldwide. He is now recognized as one of the world's leading experts on this rare developmental disorder. His team's work was instrumental in enabling the recent FDA approval of the first treatment for Rett syndrome. This monumental achievement stands on the shoulders of many milestones by Percy and the team.

In 2003, the NIH-funded Rare Disease Clinical Research Center (RDCRC) was established at UAB. As part of the RDCRC, UAB joined six other sites across the U.S. as a member of the Angelman, Rett and Prader-Willi consortium. Over the next 15 years, the RDCRC succeeded in enrolling nearly 1,000 patients to develop accurate information on the longitudinal (natural history) pattern of progression among individuals with Rett Syndrome. This work was essential to enable future clinical trials of potential therapeutics.

Rett Syndrome Natural History Study  and  Scientific Insights

In 2017, upon the seminal discoveries and scientific leadership by Percy and team, UAB was honored as one of 15 institutions across the United States with the International Rett Syndrome Foundation (IRSF) Center of Excellence designation for its dedication to providing best-in-class clinical care for Rett syndrome. In 2021, The National Organization for Rare Disorders designated UAB Medicine and Children's of Alabama as NORD Rare Disease Centers of Excellence, joining 31 medical centers to expand access, advance care and enhance research for rare diseases, like Rett Syndrome.

The groundbreaking treatment was evaluated in a randomized, double-blind, placebo-controlled, 12-week study. UAB recruited 12 participants in the study, which enrolled a total of 93 patients with Rett syndrome and 94 controls. 

The new treatment, trofinetide, marketed as Daybue, targets overall well-being in patients, reducing brain inflammation, which stops some cells from becoming too active. It also increases the amount of a protein called IGF-1. The study suggests that the drug helps neurons communicate better with each other, like they would in a healthy brain.

The substantial work to enable the natural history study and clinical trials benefitted substantially from the CCTS Child Health Research Unit, a partnership with Children’s of Alabama and the UAB Department of Pediatrics, as well as the UAB’s Civitan International Research Center Rett Syndrome Clinic.

Written by Robert Brown, April 20, 2023.