PAK (p21-activated kinase) Archives • Fragile X Research

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.

David Brown, MD, PhD, Ivan Angulo-Herrera, PhD and Anthony Hall of Healx present about the Drug Repurposing Programme for Fragile X syndrome.

Meet #FriendofFRAXA Will! If you would like to nominate someone as a #FriendofFRAXA, we welcome all who have been touched by Fragile X, including friends, grandparents, siblings, professionals and companions alike to become a #FriendofFRAXA with the goal of putting a face to Fragile X for those who may not know someone directly.

Caffeine is the most popular smart drug in the world. With a $90,000 grant from FRAXA Research Foundation, Alberto Martire, PhD and Antonella Borreca, PhD in Rome, Italy are investigating adenosine receptors antagonists to treat Fragile X syndrome. Compounds which are able to block adenosine receptors are commonly found in tea, chocolate, and coffee.

Antonella Borreca, PhD, and Alberto Martire, PhD

With a $163,356 grant from FRAXA Research Foundation in 2010-12, Dr. Scott Soderling and Dr. Hwan Kim at Duke University bred the standard mouse model of Fragile X syndrome to their lines of mice that express reduced levels of several key proteins that modulate synaptic actin. These compound mutant mice were compared to FXS mice to determine if genetically impairing pathways to the actin cytoskeleton can rescue deficits in the FXS mice.

At the start, it’s always hard to know what methods will work best for something as complex as the development of disease-modifying treatments for Fragile X. But, we’ve always tried to let the science lead us down the right path. At this point, the results are unequivocal, and they have shaped how we are looking for the Next Great Thing in Fragile X treatments.

With a $65,000 grant from FRAXA Research Foundation in 2005, Dr. Berry-Kravis at the Rush University Medical Center conducted a pilot clinical trial of lithium in 15 patients with Fragile X syndrome. Results published.

Elizabeth Berry-Kravis, MD, PhD, Fragile X researcher

With a $104,498 grant from FRAXA Research Foundation from 2003-2008, Dr. Julie Lauterborn at the University of California has done several studies on dentritic spines and finding treatment targets for memory retention in Fragile X mice.

With an $81,000 grant from FRAXA Research Foundation from 2005-2006, Dr. Susumu Tonegawa and his team at MIT studied the enzyme PAK to determine how it could be used for a treatment target. Results published.

With a $229,000 grant from FRAXA Research Foundation in 2006, Drs. Richard Paylor, David Albeck, and Francis Brennan at the Baylor College of Medicine found that, in mice as in humans, the level of Fragile X protein in brain cells plays a prominent role in determining levels of activity and anxiety.

Richard Paylor, PhD, at Baylor College of Medicine, FRAXA Research grant

A two year $62,000 FRAXA grant was been awarded to W. Ted Brown, MD, PhD from 1997-1998. The Principal Investigator at the Institute For Basic Research in New York will work to develop an improved test to show learning deficits in the FMR1 knock-out mouse model of Fragile X, and then to test the effects of experimental drugs (Ampakines) that may be effective in treating these deficits.

PAK (p21-activated kinase)

Clinical Trials and Cyclic AMP in Fragile X Syndrome: A Life Journey

Healx Drug Repurposing Programme for Fragile X Syndrome

Meet Will!

Coffee, Tea, and Chocolate: Adenosine Receptors in Fragile X

Synaptic Actin Signaling Pathways in Fragile X

What Works, and What Doesn’t

Pilot Clinical Trial of Lithium in Fragile X Shows Promising Results

AMPAkines and BDNF in Fragile X: UCI Researchers Restore Memory Process in Fragile X

Experimental Compound FRAX486 Reverses Signs of Fragile X in Mice

Therapeutic Interventions in FMR1 Knockout and Transgenic Mice: Role of the FMR1 Gene

Studies of the Fragile X Knock-Out Mouse: Improving Memory Reversal Testing and Treatment with AMPAkines