Study Supports Development of Preventative Therapies for FXTAS


In people with fragile X-associated tremor/ataxia syndrome (FXTAS), a condition related to fragile X syndrome that develops late in life, measures of dexterity and memory tend to decrease. significantly worsen over time, according to a new study.

The results support the development of preventive treatments for FXTAS, according to its researchers.

The study, “Neuropsychological changes in carriers of the FMR1 premutation and onset of fragile X-associated tremor/ataxia syndromewas published in the Journal of Neurodevelopmental Disorders.

recommended reading

Both FXTAS and Fragile X are caused by a similar type of genetic mutation – an abnormal expansion of the RMF1 embarrassed. In people without a mutation, this gene contains a section where three “letters” (CCG) of the genetic code are repeated five to 40 times. In Fragile X, there are often more than 200 such repetitions. Between these two extremes – from about 55 to 200 repetitions – is classified as a “premutation”.

“People, especially men, who have this premutation variant of the FMR1 gene are at high risk of developing FXTAS later in life,” said David Hessl, PhD, professor at the University of California Davis and co- author of the study. A press release.

While Fragile X is characterized by developmental and behavioral abnormalities present early in life, FXTAS does not appear until adulthood and is eponymously characterized by movement problems, namely tremors and ataxia (lack of control or coordination during voluntary movements). Relatively little is known about this condition, which was first formally described by UC Davis scientists in the early 2000s.

“We don’t know how to predict who will develop the disease or how quickly it will progress. Also, if we’re doing a treatment study, we don’t yet know the best ways to track response to intervention,” Hessl said. “We needed to establish key measures for clinical severity.”

To find out more, the scientists recruited 64 participants with the RMF1 premutation, who did not have FXTAS, in one study. A group of 30 participants without a premutation (controls) was also included. All participants were men, aged 40 to 80 at the start of the trial, and more than 80% were white.

Participants are monitored regularly – some have been followed for over 15 years – completing a number of neurological and psychological assessments as well as testing for the presence of FXTAS.

“The primary importance of the cohort and design of this study is the emphasis on enrollment prior to initiation of FXTAS and subsequent monitoring of changes in functioning during disease emergence,” the authors wrote. researchers.

Results showed no noticeable difference between controls and premutation carriers at age 40, but at older ages, premutation carriers tended to have more pronounced declines in visual working memory, dexterity motor, inhibitory control (ability to resist an impulse) and manual control. movement speed. After statistical corrections for confounding variables, premutation carriers still showed faster declines in motor dexterity measures.

To date, 28.1% of premutation carriers have been positively diagnosed with FXTAS after neurological examination. The data showed that, compared to those without FXTAS, people with the disease had a significantly slower manual movement speed. They also tended to show faster declines in scores related to memory and planning skills.

recommended reading
protein levels and FXTAS

“We show that compared to controls, men with the RMF1 premutation accelerated the decline of manual dexterity and some areas of executive functioning, including visual working memory, inhibitory control, and this conversion to FXTAS is associated with deterioration in inhibitory control, planning, and resolution problems, and the slowing down of manual movements,” the scientists concluded. .

According to the researchers, a remarkable finding from the dataset is that FXTAS appears to be consistently associated with worsening over time once it develops later in life. This suggests that prophylactic (preventive) treatments “could be initiated in patients thus identified as high risk, prior to the onset of FXTAS, in an attempt to halt disease progression,” they write.

Hessl said: “There are treatments in development for FXTAS that could be tried earlier in those most at risk. Starting a patient on a prophylactic regimen before they show obvious signs of disease might be more effective than waiting until they are more advanced.

Previous Eightfold AI and Deloitte Alliance Accelerate Competency-Based Talent Transformation
Next Outgoing Intelligence Community Data Chief outlines upcoming data strategy