PDE4 Archives • Fragile X Research - FRAXA Research Foundation

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

FRAXA Research Foundation Berry-Kravis, Elizabeth • FRAXA Updates March 10, 2021AMPAkines, BPN14770, lithium, 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.

Positive Results Reported in Phase II Fragile X Clinical Trial of PDE4D Inhibitor from Tetra Therapeutics

FRAXA Research Foundation Berry-Kravis, Elizabeth • Gurney Mark • Has Results • Press Release • Research Updates November 2, 2020December 21, 2020Alzheimer's, autism, BPN14770, drug tolerance, FDA, mGluR5, NIH, PDE4, Tetra Therapeutics

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.

Companies Move to Advance Potential Cognitive Treatment for Fragile X

Fragile X News Today FRAXA Updates March 13, 2020Alzheimer's, BPN14770, FDA, NIH, PDE4, Tetra Therapeutics

Tetra Therapeutics and Shionogi announced plans to expand their partnership supporting BPN14770, a treatment candidate for disorders marked by cognitive and memory deficits, including Fragile X syndrome and Alzheimer’s disease. The agreement builds on an earlier collaboration between the two companies, and aims to further accelerate BPN14770’s development and potential marketing. It is currently in clinical testing in both Fragile X and Alzheimer’s patients.

Should You Participate in a Fragile X Clinical Trial?

FRAXA Research Foundation Research Updates February 3, 2020February 4, 2020EEG, PDE4, Tetra Therapeutics

A Fragile X clinical trial of a new PDE4D allosteric inhibitor from Tetra Therapeutics is nearly complete. Right now there are 3 remaining spots open to males 18-45 years of age with Fragile X syndrome. Dr. Elizabeth Berry-Kravis at the Rush University Medical Center in Chicago is leading this trial. The drug being studied has a unique mechanism of action that might improve cognitive and memory function.

Fragile X Clinical Trial of New PDE4D Inhibitor from Tetra

FRAXA Research Foundation 2018 Grants • 2019 Grants • 2020 Grants • Berry-Kravis, Elizabeth • Clinical • Clinical Trials • Has Results • Research Grant Results • Rush University Medical Center September 15, 2019March 10, 2021Alzheimer's, BPN14770, cyclic AMP, FDA, FRAXA-DVI, NIH, PDE4, Pierce Family Fragile X Foundation, Tetra Therapeutics

FRAXA Research Foundation has funded a clinical trial of an investigational new drug, led by Dr. Elizabeth Berry-Kravis at the Rush Fragile X Clinic in Chicago. This trial will treat 30 adult males with Fragile X syndrome with a PDE4D allosteric inhibitor from Tetra Discovery Partners using in a crossover design, so that everyone gets active drug for part of the time and placebo for part of the time.

Screening 2,320 FDA-Approved Drugs for Potential Treatment of Fragile X

FRAXA Research Foundation 2018 Grants • 2019 Grants • 2020 Grants • 2021 Grants • Current Research Grants • Disease Mechanisms • Joyce, Karen • McBride, Sean • Rowan University • Treatment Targets January 9, 2019February 5, 2021autism, drug repurposing, FDA, fruit fly, lithium, metformin, mGluR, PDE4, sleep, Tetra Therapeutics

FRAXA Research Foundation has awarded a $90,000 grant to Principal Investigator Dr. Sean McBride and Postdoctoral Fellow Dr. Karen Joyce, at Rowan University, to screen all 2,320 FDA-approved drugs on both mouse and fly models of Fragile X syndrome. Those drugs which show promise will be tested in more detail for potential to treat Fragile X in humans.

Tetra Announces $40M to Advance BPN14770 for FXS and Alzheimer’s Disease

FRAXA Research Foundation FRAXA Updates • Research Updates December 19, 2018December 19, 2018Alzheimer's, BPN14770, FDA, FRAXA-DVI, PDE4, Tetra Therapeutics

Tetra Discovery Partners has signed a multi-part deal that could bring it up to $160 million, plus royalties, from Shionogi & Co, Ltd, a Japanese major research-driven pharmaceutical company. Tetra currently is conducting an investigational Phase 2 study of BPN14770 in adults with Fragile X Syndrome, an indication for which BPN14770 has received Orphan Drug Designation from the US Food and Drug Administration. This clinical trial was made possible by early work with the FRAXA-DVI and over $200,000 from FRAXA.

Research Points to Drugs which Inhibit PDE to Treat Fragile X

FRAXA Research Foundation 2016 Grants • 2017 Grants • 2018 Grants • Bardoni, Barbara • Current Research Grants • Disease Mechanisms • INSERM Valbonne, France • Maurin, Thomas • Treatment Targets November 4, 2018November 14, 2018mRNAs, PDE4, Tetra Therapeutics

FRAXA Research Foundation funded a grant of $90,000 over 2016-2018, for a postdoctoral fellowship for Thomas Maurin, PhD, working under the mentorship of Dr. Barbara Bardoni at INSERM in France. The team works on the biochemistry of the Fragile X protein. They have found that PDE inhibitors (a class of drugs) show promise as treatments for Fragile X syndrome. In related research, FRAXA is currently funding a clinical trial of PDE4D inhibitors.

Tetra Discovery Partners Initiates Phase 2 Trial of BPN14770 in Fragile X Syndrome

FRAXA Research Foundation Berry-Kravis, Elizabeth • Rush University Medical Center July 10, 2018January 14, 2019Alzheimer's, autism, BPN14770, FDA, NIH, PDE4, sleep, Tetra Therapeutics

This 2-Period Crossover Study of BPN14770 is accepting adults males with Fragile X syndrome at Rush University Medical Center in Chicago. Principal Investigator of the study is Elizabeth Berry-Kravis, MD, PhD.
A selective inhibitor of the phosphodiesterase type-4D (PDE4D), BPN14770 has shown the ability to improve the quality of connections between neurons and to improve multiple behavioral outcomes in the Fragile X mouse model.

Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

FRAXA Research Foundation 2015 Grants • Biomarkers • Completed Research Grants • Scripps Research Institute • Treatment Targets • Vanderklish, Peter September 13, 2015April 25, 2018AMPK, FDA, GSK3, metformin, mGluR, mTOR, PDE4

With a $100,000 grant from the FRAXA Research Foundation in 2015, Dr. Peter Vanderklish explored a novel strategy to treat Fragile X syndrome: AMPK activators. The good news is that there are FDA approved (for example, metformin) and naturally occurring AMPK activators (such as resveratrol, found in red wine).