Dr. Jeffrey Neul, MD, PhD, director of the Vanderbilt Kennedy Center, talks about a new treatment for children that developed Rett syndrome.
Interview conducted by Ivanhoe Broadcast News in December 2021.
What exactly is Rett syndrome and how common is it?
DR NEUL: Rett syndrome is a neurodevelopmental disorder that primarily affects girls. It occurs in about one in 10,000 live female births. The way it manifests is that children are born normally and have an apparently normal initial development. But then, when they’re about a year and a half old, they lose the ability to speak, and they lose the ability to use their hands and develop a characteristic repetitive hand movement. Furthermore, they have trouble walking.
Why is it primarily in girls?
DR NEUL: Rett syndrome primarily affects girls because it’s a mutation on the X chromosome. Girls who have Rett syndrome have a mutation in one of their copies of the gene. Girls have two X chromosomes and boys can have mutations in this gene. Typically, they’re more severely affected because boys only have one X chromosome. But we’re understanding that there are more boys who likely have these mutations than we realize. It will be important for us to develop a greater understanding of what are the features that are present in these boys and how can we identify them, because it’s likely that these boys will benefit from the types of therapies that are developed for Rett syndrome.
Are there any reasons why this happens?
DR NEUL: The predominant cause of Rett syndrome is mutations in an X-linked gene called methyl-CpG binding protein 2, or MECP2.
How does the syndrome affect the day-to-day of the patient and their families?
DR NEUL: People with Rett syndrome are impaired in all activities of daily living. They cannot feed themselves or get around or use the restroom. It has a marked impact on day-to-day life for the families. They have to provide constant care for the affected individual.
Are there any current treatments or therapies for the syndrome?
DR NEUL: Currently, all the ways we approach treating or trying to care for people with Rett syndrome are what we would call symptomatic. There’s no targeted therapy. So, we have therapies that are based on trying to improve symptoms such as constipation or seizures. We just use medicines for constipation or seizures. Or we use therapies such as speech or communication therapies to try to improve their ability to communicate. But we have no targeted therapies directly for Rett syndrome.
How is the Lavender study changing the game for Rett syndrome?
DR NEUL: The current study evaluating a drug called trofinetide was a phase three study. Previously, this drug was tested in one trial in adults and one trial in children and both of those seemed to show that this compound was safe, well tolerated, and seemed to improve various features of Rett syndrome. The current study, the phase three Lavender study, showed robustly that it improved a variety of features in Rett syndrome, both from a caregiver perspective and from a clinician perspective.
How do people with Rett syndrome function as adults?
DR NEUL: Rett syndrome is a lifelong condition. People who have Rett syndrome oftentimes grow up to be adults who have Rett syndrome, or they, unfortunately, pass earlier in life. They don’t improve in their function. They continue to have marked impairments and basically all their activities of daily living throughout their life. People who have Rett syndrome require lifelong care.
What impact can a trial, like this, have on families and the patients?
DR NEUL: There is obviously a need to have some intervention that might improve some of these core features of Rett syndrome, especially their functional skills. So, the treatment with trofinetide really offers a promise of improving the overall quality of life for the individuals who are affected, and for their families over the course of their lifetime.
How is it administered?
DR NEUL: The medicine is taken orally. It’s a liquid medicine. It’s taken twice a day.
What improvements have you seen from the study?
DR NEUL: The improvements were broad, and different people respond in different ways. But in general, it seemed to improve how alert and interactive people were, which helps improve how much they can communicate and how much they can function. So, these are key problems in Rett syndrome. Even little bits of improvements in those areas can have a marked impact on people who have Rett syndrome.
Are there any side effects that you’ve seen so far with the study?
DR NEUL: In general, the drug was well tolerated. But it does seem to be associated with higher levels of some GI issues, such as diarrhea and vomiting. We’ve been able to address those symptoms by modifying some of the medicines that we give for people who have constipation and reducing those and potentially increasing fiber in the diet and other medicines that will help decrease the diarrhea.
It’s currently up for FDA approval. How long is the process and how likely is it to get approved?
DR NEUL: The current next steps is for the company to go to the FDA and apply for a new drug application, or an NDA. That’s something that the company has announced that they’ll be doing in 2022. The overall process after that can take a while for the FDA to review it and make a decision. It looks like they have a strong package, but, of course, it will be up to the regulators to decide if the evidence is there that this provides a true benefit to people with Rett syndrome.
If it were to get approved, would it be twice a day liquid?
DR NEUL: Yes. Right now, it most likely would be approved as a twice a day liquid formulation, unless the company adds on any additional work to determine if they can change the formulation.
Is there anything you feel that people should know?
DR NEUL: I think it’s important to recognize that while Rett syndrome is a rare disorder, it’s a common rare disorder. There are a significant number of people who are affected. But the amount of people that we know are affected in this country is probably 50 percent or less of what there should be. There’s still a lot of unrecognized cases of Rett syndrome. I think it’s important for people to know with the disorder is for the families, for caregivers, for providers of health care, and therapies to understand what it is. Because now, with the development of potential therapies that might modify the course of the disease, it will be important to identify these people so we can offer them hope.
END OF INTERVIEW
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