West Des Moines, Iowa – Born in 2013, identical twins Kenzie and Kaylie Morell were hitting some, if not all, of their normal infant and toddler milestones—until they began to slip back from them. When Kenzie was around 15 months old, she started to regress. Kaylie followed a year and a half later, losing her ability to walk and speak. In 2016, both girls were diagnosed with Rett syndrome.
A rare genetic neurodevelopmental disorder, Rett syndrome is characterized by developmental regression, loss of language and hand function and impaired gait. Nearly all cases are caused by a mutation in the methyl CpG binding protein 2, or MECP2 gene, which contains instructions for the synthesis of a protein required for brain development.
A Lack of Treatments
“Regression was incredibly heartbreaking,” said the twins’ mother, Kassie Morell. “Both girls’ regressions involved inconsolable screaming, teeth grinding, hand wringing, loss of hand use, and they seemed to be in a fog and not interested in their surroundings.”
Kaylie and Kenzie have the same mutation, but it affects them to different degrees. While Kaylie learned to walk and speak (though she lost her words as she regressed), her sister is more afflicted. Kenzie never learned to crawl or walk and has always used a wheelchair. She has no functional hand use, suffers from seizures and uses a feeding tube.
When they were first diagnosed, doctors told Morell that there are no specific treatments for Rett and no cure, so they would just focus on managing the symptoms, she recalled. “So, that was really scary, just knowing that there wasn’t anything specifically for Rett syndrome.”
That all changed in March 2021 when Kenzie and Kaylie enrolled in the double-blind, Phase III Lavender trial for Daybue (trofinetide), developed by Acadia Pharmaceuticals and Neuren Pharmaceuticals. Twelve weeks later, they received their first confirmed dose of Daybue in the open-label study.
‘A Lot of Hope’
Since starting on the drug, “Both girls are more focused and responsive when we give them instructions,” Morell told BioSpace. “They have more control of their eye gaze and their facial expressions, showing happiness, sadness or interest in things. You can really see them light up now or show disappointment if they’re not happy about something. They’re just happier. They’re more energetic.”
Kaylie has regained more purposeful hand use, Morell said, and is able to turn the pages of books when they read together. Kaylie and Kenzie use eye gaze tablets to communicate, and Kaylie is beginning to use the device’s touch function. And while Morell said neither of the girls are speaking yet, “We’ve seen more vocalizations and sounds that are starting to mimic words. There’s more vocalization even between the two girls, where you can tell they’re vocalizing an entire conversation between each other in their own way and really interacting.” The Morells are pairing the drug with physical and speech therapy and “a lot of engagement.”
Trofinetide is a synthetic version of tripeptide glycine-proline-glutamate, a naturally occurring molecule. Researchers are unsure how trofinetide elicits therapeutic effects in Rett, according to Acadia, but it has been shown to be neuroprotective in animal models.
“What happens [with Rett syndrome] is that the connections between the brain cells are lost, so you still have the neurons there, but they can’t communicate with each other,” Kathie Bishop, SVP and head of rare disease and external innovation at Acadia, told BioSpace in March prior to Daybue’s FDA approval. Daybue restores those connections between cells, she said.
“Knowing that there is one drug out there that will target specific symptoms for Rett syndrome, it’s just really a relief,” Morell said. “We’re just really grateful to have that.”
Like many children their age, Kaylie and Kenzie enjoy going for walks, to museums, and to the library. “They love being around people,” Morell said. “They love being read to, and of course, they have their favorite TV shows.” A few weeks ago, the twins enjoyed going to a gala for the International Rett Syndrome Foundation. “They’re just like any little 10-year-old girls,” Morell said. “They love their jewelry and getting dressed up.” They also love the holidays and their big brother, Jackson, who is coming home for Thanksgiving after being away at college.
As Daybue is a new drug, Morell said she doesn’t know what to expect in terms of future gains, “But we do have a lot of hope, and we’re seeing good progress. It just seems to keep getting better as time goes on.”
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Heather McKenzie