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

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

FRAXA Research Foundation Berry-Kravis, Elizabeth March 10, 2021AMPAkines, BPN14770, lithium, PAK (p21-activated kinase), PDE4, Tetra Therapeutics

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.

Healx Drug Repurposing Programme for Fragile X Syndrome

FRAXA Research Foundation Research Updates • Seminar Series October 1, 2020October 1, 2020autism, drug repurposing, EEG, Healx, PAK (p21-activated kinase), Roche

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

Meet Will!

FRAXA Research Foundation #FriendofFRAXA January 15, 2020PAK (p21-activated kinase)

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.

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

FRAXA Research Foundation 2018 Grants • 2019 Grants • 2020 Grants • 2021 Grants • Borreca, Antonella • Completed Research Grants • Disease Mechanisms • Italian National Institute of Health • Martire, Alberto • Treatment Targets December 11, 2018April 5, 2022AMPAkines, BDNF, cyclic AMP, drug tolerance, glutamate, mGluR5, mRNAs, NIH, PAK (p21-activated kinase), sleep

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.

Synaptic Actin Signaling Pathways in Fragile X

FRAXA Research Foundation 2006-2010 Grants • 2012 Grants • Completed Research Grants • Disease Mechanisms • Duke University • FRAXA Research Grants • Kim, Hwan • Soderling, Scott September 11, 2012April 25, 2018CYFIP, mGluR, mRNAs, PAK (p21-activated kinase)

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.

What Works, and What Doesn’t

Michael Tranfaglia, MD Research Updates September 7, 2012April 8, 2022Alzheimer's, AMPAkines, autism, BK channel, cancer, ERK, GABA, GSK3, lithium, mGluR5, minocycline, PAK (p21-activated kinase)

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.

Pilot Clinical Trial of Lithium in Fragile X Shows Promising Results

FRAXA Research Foundation 2001-2005 Grants • Berry-Kravis, Elizabeth • Clinical • Has Results • Research Grant Results • Rush University Medical Center • Trials and Studies November 14, 2010May 20, 2020lithium, minocycline, NIH, PAK (p21-activated kinase)

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.

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

FRAXA Research Foundation 2001-2005 Grants • 2006-2010 Grants • Disease Mechanisms • Lauterborn, Julie • Research Grant Results • Treatment Targets • University of California, Irvine February 14, 2008August 5, 2021AMPA, AMPAkines, BDNF, glutamate, mGluR5, PAK (p21-activated kinase)

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.

Experimental Compound FRAX486 Reverses Signs of Fragile X in Mice

FRAXA Research Foundation 2001-2005 Grants • 2006-2010 Grants • Disease Mechanisms • Massachusetts Institute of Technology (MIT) • Research Grant Results • Tonegawa, Susumu February 13, 2006April 27, 2021PAK (p21-activated kinase)

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.

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

FRAXA Research Foundation 1994-2000 Grants • 2001-2005 Grants • 2006-2010 Grants • Albeck, David • Baylor College of Medicine • Brennan, Francis • Completed Research Grants • Disease Mechanisms • Paylor, Richard • Treatment Targets February 13, 2006April 25, 2018AMPAkines, BDNF, PAK (p21-activated kinase), seizure, startle

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.

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

FRAXA Research Foundation 1994-2000 Grants • Completed Research Grants • New York State Institute for Basic Research • Treatment Targets June 27, 1998December 10, 2019AMPAkines, PAK (p21-activated kinase)

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.