A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2021 | Number 2, Volume 35

Alzheimer’s drug appears to benefit adult men with fragile X

A drug intended to help people with Alzheimer’s disease may also be beneficial for individuals with fragile X syndrome, according to a new study. 

Fragile X syndrome is the most common known genetic cause of autistic-like symptoms and the most common cause of inherited intellectual disability. It affects about 1 in 4,000 males and 1 in 8,000 females. 

In a 24-week randomized, placebo-controlled, two-way crossover study, Elizabeth Berry-Kravis and colleagues tested the Alzheimer’s drug, called BPN14770, on 30 adult male patients with fragile X syndrome. Study coauthor Mark Gurney became interested in the drug when he learned that both autism and Alzheimer’s affect a substance called cyclic AMP (cAMP), which helps transmit messages inside cells and plays a critical role in memory formation. Researchers in Germany had developed BPN14770 to inhibit the activity of an enzyme called PDE4D, increasing the levels of cyclic AMP in the brain. 

The drug was first tested on animals before being tested on humans. Unlike several other drugs that worked well in animal models but were ineffective in people with fragile X syndrome, BPN14770 appears to be effective for both animals and humans. 

The researchers found that cognitive scores increased by about 10% in participants receiving the drug, and language and daily functioning skills improved significantly. Moreover, no differences in side effects were seen between the active and placebo groups. 

Berry-Kravis says, “The majority of clinical outcome measures were in favor of the drug. These measures included performance-based assessments, biomarkers, and parent and physician-rated scales, which in combination suggest a meaningful impact on the global [fragile X] disease process.” She adds that it is exciting that the drug “potentially addresses a core biochemical deficit in [fragile X], a deficiency of cAMP,” which has been documented in individuals with fragile X syndrome. The researchers note, however, that larger trials are needed.


“Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebocontrolled, phase 2 clinical trial,” Elizabeth M. Berry-Kravis, Mark D. Harnett, Scott A. Reines, Melody A. Reese, Lauren E. Ethridge, Abigail H. Outterson, Claire Michalak, Jeremiah Furman, and Mark E. Gurney, Nature Medicine, April 29, 2021 (online). Address: Elizabeth Berry-Kravis, Department of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL 60612. 


“Treatment found to improve cognitive function in patients with fragile X syndrome,” news release, Rush University Medical Center, April 29, 2021. 


“An Alzheimer’s drug may boost cognition in people with fragile X syndrome,” Jon Hamilton, NPR, April 30, 2021.