Case of woman, 63, shows approved Rett therapy may benefit older adults
'Remarkable' reduction in hard-to-treat seizures seen for US patient
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A woman in her 60s with Rett syndrome and long-standing, difficult-to-treat epilepsy experienced a “remarkable” reduction in seizures after starting treatment with Daybue (trofinetide), according to a case report from a trio of U.S. researchers.
The woman, who was only officially diagnosed with the rare genetic disease at age 55, saw her seizures stop almost completely after receiving the approved Rett medication, the team reported. She also experienced a reduction in repetitive behaviors, agitation, and constipation.
“This case suggests that while published experiences with [Daybue] have primarily been in children and younger adults with [Rett], older adults may also experience meaningful clinical benefits” with the drug’s use, the scientists wrote.
While noting that “clinical trials have not reported a significant effect of [Daybue] on seizure control,” the researchers pointed out that seizures affect an estimated 50% to 90% of people with Rett, calling it “a significant aspect” of the disease.
The woman’s case was described in a clinical letter, titled “Remarkable seizure reduction with trofinetide treatment in an adult with Rett syndrome: A case report,” which was published in Seizure: European Journal of Epilepsy.
Rett, which primarily affects girls and women, is usually caused by mutations in MECP2, a gene that encodes a protein needed for nerve cells to communicate. Children with Rett often develop normally at first, reaching typical milestones. Then, however, development stops and previously acquired skills are rapidly lost. Later, some symptoms may ease, but other issues often worsen, and new ones may emerge during adolescence and adulthood.
The active ingredient in Daybue, a daily treatment from Acadia Pharmaceuticals, is a lab-made version of insulin-like growth factor 1, a molecule that is important for the brain to develop and function normally. Daybue is thought to help nerve cells form healthier connections, supporting the brain’s ability to adapt and learn, which in turn is expected to reduce Rett symptoms.
Both Daybue, a ready-to-use liquid, and Daybue Stix, its powder formulation, are approved in the U.S. to treat individuals ages 2 and older who have been diagnosed with Rett.
Woman averaged 26 seizures per month before Daybue
While clinical studies of Daybue have mainly involved younger patients, this report described a 63-year-old woman with Rett who was started on the treatment at a much older age. She had developed normally during early childhood but began losing fine motor skills and speech at age 2. She also returned to bottle feeding at that time. At age 3, she was diagnosed with intellectual disability and autism.
Over time, she developed increasing cognitive difficulties and spastic diplegia, which causes stiffness in the legs. At age 13, she developed epilepsy, which remained difficult to control in the ensuing years despite antiseizure medications. The patient was also put on a low-carbohydrate, high-fat diet, which is sometimes used to help control treatment-resistant epilepsy.
Lacosamide became her most effective and best-tolerated antiseizure medication, but even at 500 mg per day, she continued to have as many as four seizures each day, averaging 26 seizures each month. A video electroencephalogram, a diagnostic test that records the electrical activity of the brain while observing a patient’s behaviors, confirmed the characteristic electrical pattern during a seizure.
The woman also had severe constipation and had tried many treatments, including medications that increase bowel movements, stool softeners, laxatives, and antibiotics. Probiotics had also failed to ease her symptoms.
Her seizures and constipation were serious enough to result in frequent visits to the emergency department. She also bit her hands and experienced nighttime agitation that could keep her awake for hours.
Genetic testing after age 50 confirmed woman’s Rett diagnosis
Although her symptoms had been present for decades, the woman’s Rett diagnosis was not confirmed until she was in her mid 50s, when genetic testing identified a mutation in the MECP2 gene. At age 61, after discussion with her parents, who were her legal guardians, doctors started treatment with Daybue at 12,000 mg twice daily. The woman “remains on this dose,” the researchers noted.
The response was much broader than expected, according to the scientists, from Thomas Jefferson University Hospital in Philadelphia. The team noted that, after starting Daybue, the woman became almost seizure-free. She experienced three clusters — multiple seizures occurring close together in time — over the following period, including one during a urinary tract infection and another after her lacosamide was temporarily reduced to a lower dose. Eventually, the woman was experiencing about two seizures each year.
Her nighttime agitation also became less frequent, her sleep became more consistent, and her caregivers reported that she rested better. Her constipation resolved completely. Her repetitive hand-biting behavior also stopped, so she no longer needed the protective soft glove she had previously worn.
She no longer required emergency care after starting Daybue, and occasional diarrhea was the only reported side effect, which was manageable, according to the team. After 27 months, or 2.4 years of treatment, she remained clinically stable.
“We are not aware of a similar case of an older individual with [Rett] with significant seizure reduction after starting [Daybue],” the researchers wrote.
The team noted that, because seizures returned when lacosamide was temporarily reduced, it is possible that Daybue may have a “synergistic effect” with some antiseizure medications. That means that their combined benefit may be greater than the sum of the benefits of each treatment alone. However, further studies are needed to determine how well Daybue works in combination with other antiseizure medications, the researchers noted.
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