Clinical Relevance: New treatments and some clinical trials show promise for treating Rett syndrome
- Rett syndrome is a rare neurodevelopmental disorder affecting approximately 1 in 10,000 live female births.
- The disease seems to be caused by mutations in MECP2, a protein is crucial for regulating the activity of genes of the nervous system.
- There is no cure for Rett syndrome, but patients have better quality of life thanks to new advancements and care by a multidisciplinary team.
Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting approximately 1 in 10,000 live primarily female births. According to a recent National Institutes of Health report, advances in genetic testing and phenotypic identification have revealed some extremely rare cases of males with a similar phenotype.
RTT is typically characterized by a period of normal development after birth, followed by regression in speech and hand movements, gait abnormalities, erratic hand movements, and deceleration of head growth. Other diagnostic criteria for RTT include irregular breathing, gastrointestinal and musculoskeletal disorders, seizures, poor sleep, reduced response to physical pain, and behavioral issues.
Understanding Rett Syndrome
Rett syndrome seems to be caused by mutations in the Methyl-CpG binding protein 2 (MECP2.) This protein is crucial for regulating the activity of genes involved in nervous system development and function.
As a disorder marked by various comorbidities, RTT treatment requires a multidisciplinary approach:
- Neurologists may treat a patient’s seizures.
- Psychiatrists can offer psychological support.
- Sleep medicine specialists may sometimes manage mood and sleep disorders.
- Respiratory therapists, cardiologists, gastroenterologists, and orthopedists often round out the medical care team. There is no cure for Rett syndrome. But certain comorbidities typically associated with RTT are treatable. There are, for example, medications for epilepsy and anxiety-related GI and respiratory issues.
Parents and caregivers can help ensure patients receive the best care by keeping meticulous records of health documents and ensuring patients receive regular wellness checks, immunizations, and annual ECGs to monitor QTc intervals.
Potential Treatments
The average lifespan for RTT patients is currently 50-years old. Emerging treatments signal a brighter future ahead.
One recent development is the use of a drug called IGF-1 (insulin-like growth factor 1.), In some studies, the therapy improved brain function and communication skills in individuals with Rett Syndrome. Gene therapy is also showing some promise. By modifying or replacing defective genes, scientists can correct the underlying genetic cause of the disorder.
And another promising development last month. Acadia Pharmaceuticals announced that their investigational drug, Trofinetide, was the first-ever drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of Rett syndrome. Sold under the name, DABUE, the medication works by reducing inflammation in the brain, stopping certain types of cells from becoming overactive, and increasing the amount of the naturally occurring IGF-1. In clinical trials, subjects taking Trofinetide saw improvement across several key areas, including social communication, fine motor skills, and breathing.
In addition to these medical treatments, there are also some non-medical interventions that may be helpful in managing Rett Syndrome symptoms. For example, physical therapy can help improve mobility and motor function, while speech therapy can help with communication skills. Assistive technology devices, such as eye-tracking communication systems, can also help individuals with Rett Syndrome communicate more effectively.
Learn More
In this accredited activity for CME Institute, Alan Perc, MD, Amitha Ananth, MD, and nurse practitioner Jane Lane from the University of Alabama, Birmingham discussed how physicians can better support patients with RTT. The goal, they said, is to optimize care to improve quality of life.
“Hope is on the horizon that these emerging drug treatments will be available for patients in the near future and that gene therapy will become a reality in the next year or so,” Percy said.
To learn more about the latest updates in RTT and earn free CME credits, complete these activities:
FAQs
While there is no cure for Rett syndrome, in 2023, the U.S. Food and Drug Administration (FDA) approved a new drug, Trofinetide, to treat Rett syndrome in children age two and older.
What is the new medicine for Rett syndrome? ›
Trofinetide is the first drug approved by the FDA to treat Rett Syndrome in children aged 2 years or above. The drug significantly improved Rett syndrome behavioral scores Rett syndrome behavioral questionnaire in clinical studies.
Can gene therapy help Rett syndrome? ›
Gene therapy has the potential to treat Rett syndrome comprehensively. This is because almost all cases of Rett syndrome are caused by mutations found on an X chromosome gene called methyl CpG binding protein, or MECP2. This gene typically encodes a protein (MeCP2) which is essential for brain development.
Are there any treatments or cures for Rett syndrome? ›
Though medications can't cure Rett syndrome, they may help control some signs and symptoms that are part of the disorder. Medications may help with seizures, muscle stiffness, or problems with breathing, sleep, the gastrointestinal (GI) tract or the heart.
How old do girls with Rett syndrome live? ›
While it is known that Rett syndrome shortens lifespan, not much is known about specific life expectancy rates for people with Rett syndrome. It generally depends on the age when symptoms first begin and their severity. On average, most individuals with the condition survive into their 40s or 50s.
What is reverse Rett syndrome? ›
Reverse Rett is a patient advocacy and research organisation focused on accelerating treatments and a cure for Rett syndrome to everyone affected. The UK Rett Syndrome community is at a pivotal moment at the moment with two clinical trials of gene therapies underway.
How close is a cure for Rett syndrome? ›
There is no cure for Rett syndrome, but patients have better quality of life thanks to new advancements and care by a multidisciplinary team.
How much does the Rett syndrome drug cost? ›
The list price of Daybue will be $21.10 per milliliter, or an estimated average net realized cost to payors of about $375,000 annually, Brendan Teehan, executive vice president, chief operating officer and head of commercial at Acadia, told Formulary Watch.
What is the orphan drug for Rett syndrome? ›
Recently, Trofinetide received the US Food and Drug Administration (FDA) approval and orphan drug designation for the treatment of RTT, making it the first approved drug for this rare genetic disorder.
Is Rett syndrome caused by inbreeding? ›
In nearly all cases, the genetic change that causes Rett syndrome is spontaneous, meaning it happens randomly. Such random mutations are usually not inherited or passed from one generation to the next.
Challenges for gene therapy. One of the greatest known challenges to delivering a permanent, “for ever”, cure for Rett syndrome comes from what scientists call the 'Goldilocks principle'. That is, the amount of protein needs to be just right in each brain cell, as too much MECP2 protein can be as bad as too little.
Can people with Rett syndrome have children? ›
Rett syndrome patients are fertile but unlikely to have children. Therefore the mutations are rapidly lost from the human gene pool. More than 60 mutations have been identified that cause Rett syndrome.
What is stage 4 of Rett syndrome? ›
Other symptoms of Rett syndrome may occur. stage 3 – plateau stage – abilities stabilise; intensity of symptoms may lessen. This stage can last for years. stage 4 – late motor deterioration (loss of movement) – begins between five and 25 years of age, can last for decades but may not occur in all individuals.
Is Rett syndrome still considered autism? ›
While Rett syndrome may not officially be an ASD in the DSM-5, the link to autism remains. Many children are diagnosed as autistic before the MECP2 mutation is identified and then the diagnosis is revised to RTT. Autistic traits do occur, especially during the regression, and sometimes these traits do persist.
Is Rett syndrome painful? ›
There are numerous chronic health and behavior problems associated with RTT for which it would be reasonable to expect pain or discomfort (e.g. scoliosis, constipation and related gastrointestinal problems, self-injurious behavior).
Could this disorder have been prevented Rett syndrome? ›
Prevention. There's no known way to prevent Rett syndrome. In most cases, the genetic changes that cause the disorder occur spontaneously. Even so, if you have a child or other family member with Rett syndrome, you may want to ask your health care provider about genetic testing and genetic counseling.
Is Rett syndrome life ending? ›
The long-term effects of Rett syndrome can vary significantly. Almost all people with Rett syndrome will need caregiver support for their whole life. Many people with Rett syndrome live a high quality of life well into their 40s and beyond. For some people, other health complications may shorten life expectancy.
