An experimental treatment produced improvements in cognitive function and language in patients with fragile X syndrome, according to study results published on April 29 in Nature medicine. Fragile X syndrome (known as FXS for short) is the most common known genetic cause of autism and the most common cause of inherited intellectual disability.
“These findings offer hope for patients with fragile X syndrome and their families,” said Elizabeth Berry-Kravis, MD, PhD, pediatric neurologist at Rush University Medical Center and lead investigator of the study. “The majority of clinical outcome measures were in favor of the drug. These measures included performance-based ratings, biomarkers and scales rated by parents and physicians, which in combination suggest a significant impact on the overall process. of FXS disease. “
The study was a phase two clinical trial to evaluate the safety and effectiveness of a drug known as BPN14770 in 30 men aged 18 to 41 with fragile X syndrome. BPN1477 inhibits the activity of an enzyme known as phosphodiesterase-4D (PDE4D), which controls the availability in the brain of cyclic adenosine monophosphate (cAMP), a molecule critically involved in the formation of memory. By inhibiting PDE4D, the drug increases cAMP levels in the brain. “It’s exciting that we have a drug that potentially responds to a basic biochemical FXS deficiency, cAMP deficiency, which has been documented in patients, and which I discovered during my pediatric neurology internship there. is 30 years old, ”said Berry-Kravis.
Study participants received daily oral doses of BPN14770 twice a day or placebo for 12 weeks. Parents, caregivers, and reviewing physicians did not know whether the participants received the treatment or the placebo.
The study assessed participants using a cognitive battery version of the National Institutes of Health (NIH) Toolkit (a cognitive measure) which, in a collaborative work with Dr. David Hessl at the UC Davis MIND Institute, has been modified to be effective in assessing people with intellectual disabilities. In addition, the study included scales on which parents rated improvements in the drug.
“This is the first time that the NIH Toolkit can be used to demonstrate cognitive change in a trial in people with developmental disabilities,” said Berry-Kravis. “In just three months, we saw improvement, particularly in the NIH Toolkit verbal subtests, coupled with parents’ assessment of improvements, especially in language.
Cognitive assessments using the NIH Toolbox revealed significant benefits in oral reading recognition, picture vocabulary, and crystallized composite cognition score. Parent / guardian reviews revealed clinically significant benefits in terms of language and day-to-day functioning.
After 12 weeks of treatment in the study, the patients crossed over and took a placebo if they had taken the drug, and drug if they had taken a placebo for an additional 12 weeks. The benefit of BPN14770 was shown to persist for up to 12 weeks after switching from the drug to placebo. BPN14770 was very well tolerated with few adverse events.
In laboratory studies, BPN14770 promoted the maturation of connections between neurons (which is impaired in patients with fragile X syndrome). BPN14770 is developed by Tetra Therapeutics for the treatment of Fragile X Syndrome. The drug’s mechanism of action may also have the potential to improve cognitive and memory function in Alzheimer’s disease and other dementias, learning / developmental disabilities, and schizophrenia. At this time, however, the United States Food and Drug Administration has only approved BPN14770 for experimental use, and it will be important to conduct larger controlled studies in fragile X syndrome to confirm the cognitive benefits of the drug. drug.
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Material provided by Rush University Medical Center. Original written by Nancy Difiore. Note: Content can be changed for style and length.