Pediatric clinic for Rett syndrome draws patients for multispecialty care, clinical trials

Families that have a child with Rett syndrome, a rare neurological disorder that almost exclusively affects females, often travel hundreds of miles to the Rett Spectrum Clinic in St. Louis — a collaboration between Washington University School of Medicine and St. Louis Children’s Hospital — for multispecialty care and access to innovative clinical trials.

That includes Erica and Chad Waggenspack of Baton Rouge, La., whose youngest daughter, Kerrigan, 4, was diagnosed with Rett as a 2-year-old. The condition affects brain development, altering all aspects of a child’s life. The family makes the trek to St. Louis at least twice a year to be seen by a care team that includes pediatric neurologists, dietitians, speech therapists and augmentative communication specialists, occupational therapists and physical therapists — all in a single four-to-five-hour visit. While most patients at the clinic come from Missouri, Illinois, Arkansas, Kansas and Nebraska, others travel from as far away as Florida, Washington, Arizona and even India.

Rett syndrome is caused a genetic mutation on the X chromosome and affects about one in 10,000 females and even fewer males. Children born with the condition appear healthy as infants but often miss major milestones such as sitting up or crawling. Over time, they lose the ability to speak, walk, eat and can develop breathing difficulties. There is no cure. Specialty care such as that provided at the WashU Rett Spectrum Clinic is a lifeline for families, and many choose to participate in clinical trials.

In fact, the first potential drug treatment for Rett syndrome has been granted priority review by the Food and Drug Administration (FDA), and Washington University physicians at the Rett Spectrum Clinic had a hand in getting it there. Phase 3 clinical trial results show that the drug – trofinetide – improved behavior and communication, based on objective measures. The drug is designed to reduce neuroinflammation and support nervous system connections. The WashU Rett Spectrum Clinic at St. Louis Children’s Hospital was a site for the trial.

“This is a pivotal moment in Rett syndrome,” said Robin C. Ryther, MD, PhD, associate professor of neurology at Washington University and director of the clinic. “The drug is not a cure-all, but results of the trial showed statistically significant improvement in the ability to communicate, in behavior, and their overall well-being. Anecdotally, families felt like it made a difference.”

Ryther and Judith L. Weisenberg, MD, associate professor of neurology, opened the clinic in 2015. At the time, there were only three in the country. Now, there are more than a dozen across the U.S., but the WashU clinic is known for its multidisciplinary, specialty care.

“Rett syndrome is a whole-body disorder,” Ryther said. “While the genetic mutations that cause the condition initially alter brain development, Rett affects every system in the entire body. So, patients really need comprehensive care by team specialists who understand the condition and the way it affects all aspects of a child’s life.”

Added Weisenberg: “When a patient comes here, the idea is to make sure they are getting comprehensive care to optimize their health, their development and their ability to function in everyday life as much as possible.”

A key feature of the Rett clinic is its involvement in clinical trials aimed at understanding the trajectory of symptoms over time – most patients live into adulthood – and evaluating investigational drugs as potential therapies.

Observational studies help to determine patterns in symptoms and the slowing of abilities over time. It is the critical foundation for assessing whether investigational drugs evaluated in therapeutic trials are able to alter the disorder’s symptoms. The Rett Spectrum Clinic and its patients have been involved in several therapeutic drug trials, but the team is most excited about the trofinetide trials. If the FDA approves trofinetide – a decision is expected in the spring – it will be the first drug treatment available for Rett syndrome.

The phase 3 double-blind, randomized, placebo-controlled trial, sponsored by Acadia Pharmaceuticals, involved 187 girls and women ages 5 to 20, at 21 study sites. Based on promising data from the trial, the drug was made available through an open-label extension study to all patients enrolled in the phase 3 trial and to girls as young as 2. The extension study also was designed to look at the safety and tolerability in this younger age group and to provide information to guide dosing.

The Rett Spectrum Clinic in St. Louis enrolled 15 participants in the trofinetide trials. Kerrigan, the 4-year-old spitfire from Baton Rouge, was enrolled in the open-label extension study. Her mom, Erica, said she has “just blossomed with the drug. We have found that she says more words. She’s had a bit of a more diverse vocabulary. While taking the drug, she could also walk to the bathroom sometimes when she needed to go the potty. It’s not a miracle drug or cure by any means, but it’s a step in the right direction.”

Waggenspack said she and her husband bring Kerrigan to the Washington University Rett Spectrum Clinic because they “didn’t want to just be a number. We wanted someone who would actually care about our family and Kerrigan getting the best care, and we have truly found that in St. Louis.”

Another strength of the clinic is that it helps educate other physicians and health-care providers about the condition, as well as teachers and family members so children can live as normal lives as possible, given the challenges of Rett. The clinic team also reaches out to patients’ schools and local care teams. “Our goal is to help the local care teams – they are really the everyday care teams – believe in these children and help them take the next steps and experience life as much as possible,” Ryther said.

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