A $200K FRAXA grant enabled a successful Phase 2 trial of a PDE4D inhibitor for adult men with Fragile X, showing strong cognitive gains without side effects or tolerance.
Dr. Mark Gurney, CEO of Tetra Therapeutics, discusses how one of the earliest clues to the biology of Fragile X led to the most successful Fragile X clinical trial to date. FRAXA and Tetra began working together after a key FRAXA-funded study caught the attention of Dr. Gurney. Through the FRAXA Drug Validation Initiative, Dr. Patricia Cogram was able to conduct preclinical validation experiments with Tetra’s lead compound in record time, paving the way for clinical trials.
In November 2020, a phase II clinical trial reported extremely successful results. This clinical trial of a PDE4D inhibitor from Tetra Pharmaceuticals was conducted by Dr. Elizabeth Berry-Kravis at Rush University Medical Center and funded by FRAXA Research Foundation. In this Simons Foundation lecture, Elizabeth Berry-Kravis traces 30 years of Fragile X research, from identifying its cause, through finding dozens of treatment targets, through a series of disappointing clinical trials.
Today, Tetra Therapeutics announces the first unequivocally positive phase 2 clinical trial in Fragile X syndrome, press release below. The results do not depend on carving out a subset of patients or post hoc analysis.
FRAXA funded a screen of 2,320 FDA-approved compounds in the Fragile X fly model to identify hits that improve memory and social behavior for advanced testing.
Could “caffeine-like” drugs help Fragile X? FRAXA funded research to test adenosine blockers, which may boost thinking and improve symptoms in Fragile X mice.
FRAXA-funded work identified PDE enzymes as key targets in Fragile X, showing that PDE inhibitors can fix signaling and boost synaptic function. PDE4D trials are underway.
Dr. Maurin and Dr. Bardoni were awarded $90,000 over two years from FRAXA Research Foundation for their project, “Modulating cAMP And cGMP Levels As A New Therapeutic Approach For FXS”, in May 2016. They aim to gain a better understanding of how the brain develops and functions Like snowflakes, people with Fragile X Syndrome are not all alike. Some respond differently to the same drugs, as previous Fragile X research has shown. Understanding this phenomena is leading French scientists Barbara Bardoni, PhD, and Thomas Maurin, PhD, to identify new drugs to improve treatments in patients with Fragile X.
Loss of FMRP disrupts dopamine-driven reward function—Fragile X mice show impaired cocaine sensitization and place preference, revealing new plasticity defects.
Using a fruit-fly Fragile X model, researchers screened many drugs quickly to find those that improve behavior, speeding up potential treatment testing.
Fragile X mice show reduced basal cAMP and exaggerated mGluR-LTD; boosting cAMP or blocking specific adenylyl cyclases rescues synaptic and behavioral defects.
FRAXA-funded research by Dr. Anita Bhattacharyya at the Waisman Center revealed key insights into cyclic AMP signaling in Fragile X. Findings were published.
