FRAXA Drug Validation Initiative (FRAXA-DVI) Provides Preclinical Testing of Potential Fragile X Treatments
Patricia Cogram, PhD
Principal Investigator
IEB, University of Chile
Santiago, Chile
Robert Deacon, PhD
Co-Principal Investigator
University of Oxford
Oxford, United Kingdom
Paulina Carulo, MD
Collaborator
FLENI Institute
Buenos Aires, Argentina
2025 Grant Funding: $60,000
Continuously Funded by FRAXA Since 2011
Summary
FRAXA-DVI is a cost-effective, streamlined preclinical platform at the University of Chile for assessing the potential of investigational new drugs and repurposed compounds to treat Fragile X. It is the cornerstone of FRAXA’s community-based drug development program to accelerate the discovery of effective Fragile X syndrome (FXS) treatments.
Spearheaded by FRAXA Research Foundation in 2011 and funded every year since, including $60,000 in renewed support for 2025, FRAXA-DVI is one of FRAXA’s longest-running and most impactful research initiatives. It has evaluated hundreds of potential treatments, enabling major clinical development programs, including some now in Phase 3 clinical trials.
Virtually every investigational new drug in development for Fragile X has been tested at FRAXA-DVI.
Working with FRAXA-DVI
At FRAXA-DVI, scientists run dozens of experiments on compounds, evaluating their potential to correct Fragile X-related deficits. Some drugs tested here were discovered through FRAXA-funded research, while others originated from pharmaceutical pipelines for different conditions and show promise for Fragile X.
The team is led by Dr. Patricia Cogram, Associate Professor of Genetics at the University of Chile, whose pioneering work has made FRAXA-DVI a critical resource in the global Fragile X research pipeline. Dr. Robert Deacon has over forty years of experience in rodent behaviour as the head of the rodent behavior unit at Oxford University. Collaborator Dr. Paulina Carulo leads a Fragile X clinic in Argentina, and this direct connection with individuals and families affected by Fragile X provides crucial insights.
Discover how FRAXA-DVI transforms discoveries into real-world results in our feature story Inside the FRAXA Drug Validation Initiative.
Interested in collaborating or supporting our work? Contact Patricia Cogram at FRAXA-DVI or Michael Tranfaglia at FRAXA to explore how we can advance Fragile X treatments together.
We have run hundreds and hundreds of compounds through FRAXA-DVI. We can now tell which pathways are critical for Fragile X. The changes aren’t just in behavior, but also in the brain’s connectivity.
Patricia Cogram, PhD
Director, FRAXA-DVI
The FRAXA-DVI Process: How We Test Potential Treatments
The FRAXA-DVI process takes just six weeks, representing a small investment in time to advance lifesaving treatments.
Identifying Promising Compounds
Candidate drugs come from academic researchers, pharmaceutical companies, and FRAXA-funded projects.
Preparing Fragile X Mouse Models
Testing is conducted on FMR1 knockout mice, the gold-standard preclinical model for Fragile X.
Establishing a Baseline
Before treatment, mice undergo behavioral testing to assess their initial cognitive and physiological state.
Administering the Drug
The candidate compound is given to the mice over a specific timeframe, with careful monitoring of:
- Daily responses
- Side effects
- Weight changes
Behavioral, Blood & Brain Analysis
Statistical evaluation determines whether the compound positively impacts Fragile X symptoms:
- Behavioral tests to measure learning, memory, and aberrant behaviors
- Biomarker studies
- Post-mortem brain analysis for protein and gene expression changes
Translating Research to Action
A comprehensive report is compiled and reviewed by FRAXA in collaboration with pharmaceutical and academic scientists, to determine next steps:
- Should the drug progress toward clinical trials?
- Is additional testing needed?
Featured Publications from FRAXA-DVI Studies
Gurney ME, Cogram P, Deacon RM, Rex C, Tranfaglia M.
Sci Rep. 2017 Nov 7Not every compound tested at FRAXA-DVI leads to success, but when one does, the impact can be profound.
One of the most exciting stories to emerge from FRAXA-DVI is Shionogi's zatolmilast, a phosphodiesterase-4D inhibitor.
Detailed testing showed that zatolmilast improved cognition & memory and additional symptoms in Fragile X mice.Zatolmilast is now in phase 3 clinical trials for Fragile X!
- Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in Fragile X syndrome mice
Hurley MJ, Deacon RMJ, Chan AWE, Baker D, Selwood DL, Cogram P.
Brain. 2022 Mar 29VSN16R is a cannabinoid-like compound that activates BK channels in the brain. Studies at FRAXA-DVI showed that chronic treatment with VSN16R can rectify behavioral and cognitive defects in a mouse model of FXS.
Following these studies, Spinogenix reported topline results of a phase 2 clinical trial in Fragile X syndrome.
Cogram P, Deacon RMJ, Klamer D, Rebowe N, Sprouse J, Reyes ST, Missling CU, Kaufmann WE.
Am J Med Genet A. 2022 AugBlarcamesine is being developed by Anavex for the treatment of Alzheimer's disease, Fragile X syndroime, and other disorders.
Tranfaglia MR, Thibodeaux C, Mason DJ, Brown D, Roberts I, Smith R, Guilliams T, Cogram P.
Neuropharmacology. 2019 Mar 15AI-based technologies like Disease-Gene Expression Matching (DGEM) may allow for rapid identification of promising repurposing candidates. A DGEM study conducted by Healx and funded by FRAXA predicted that sulindac could be therapeutic for Fragile X, and subsequent preclinical validation studies have shown promising results. Metformin was confirmed as another promising candidate drug.
The use of combinations of available drugs and nutraceuticals could greatly expand the options for repurposing and may be a viable business strategy.
Chadwick W, Angulo-Herrera I, Cogram P, Deacon RJM, Mason DJ, Brown D, Roberts I, O'Donovan DJ, Tranfaglia MR, Guilliams T, Thompson NT.
Brain Commun. 2024 Jan 15A treatment strategy predicted by Healx Artificial-Intelligence methods and funded by FRAXA uses the combination of gaboxadol and ibudilast.
Studies at FRAXA-DVI found that daily treatment with ibudilast and gaboxadol rescued cognitive deficits and abnormal behaviors in a Fragile X syndrome mouse model. No evidence of tolerance and no adverse effects were seen.
Cogram P, Deacon RMJ, Warner-Schmidt JL, von Schimmelmann MJ, Abrahams BS, During MJ.
Front Behav Neurosci. 2019 Jun 25FRAXA-DVI studies reported that treatment with gaboxadol normalized all of the aberrant behaviors observed in Fmr1 KO2 mice. These results enabled a phase 2 clinical trial of gaboxodol in Fragile X.
Deacon RM, Glass L, Snape M, Hurley MJ, Altimiras FJ, Biekofsky RR, Cogram P.
Neuromolecular Med. 2015 Mar 17These studies at FRAXA-DVI led to a phase 2 clinical trial of trofinetide in Fragile X . In 2023 trofinetide became the first FDA-approved treatment for Rett Syndrome.
