2017 Grants Archives • Fragile X Research

FRAXA Drug Validation Initiative (FRAXA-DVI)

FRAXA Research Foundation 2011 Grants • 2012 Grants • 2013 Grants • 2014 Grants • 2015 Grants • 2016 Grants • 2017 Grants • 2018 Grants • 2019 Grants • 2020 Grants • 2021 Grants • Biomarkers • Carullo, Paulina • Cogram, Patricia • Current Research Grants • Deacon, Robert • Drug Repurposing • FLENI Foundation • Research Resources • University of Chile • University of Oxford May 6, 2021May 6, 2021BPN14770, drug repurposing, EEG, FRAXA-DVI, Healx, microbiome, Neuren Pharmaceuticals, NIH, Ovid Therapeutics, PDE4, Tetra Therapeutics, trofinetide

The FRAXA Drug Validation Initiative (FRAXA-DVI) provides speedy, cost-effective, objective preclinical testing of potential Fragile X treatments. FRAXA-DVI uses in-vitro systems, behavior batteries, and gene expression and peripheral biomarker platforms to validate investigational new drugs and repurposed available compounds in Fragile X syndrome (FXS).

Clinical Study of Non-Invasive EEG for Children Ages 2-7

FRAXA Research Foundation 2017 Grants • 2018 Grants • 2019 Grants • 2020 Grants • 2021 Grants • Biomarkers • Boston Children's Hospital • Clinical • Current Research Grants • Has Results • Nelson, Charles A. • Recruiting • Research Updates • Trials and Studies • Wilkinson, Carol March 5, 2021March 10, 2021autism, EEG, Pierce Family Fragile X Foundation, sound

Dr. Carol Wilkinson, MD PhD, and Dr. Charles Nelson, PhD, at Boston Children’s Hospital are recruiting children ages 2-7 years with Fragile X syndrome to participate in a study of brain differences using non-invasive EEG.

Auditory Dysfunction in Fragile X Syndrome in a Mouse Model of Fragile X

FRAXA Research Foundation 2017 Grants • 2018 Grants • Biomarkers • Disease Mechanisms • Klug, Achim • McCullagh, Elizabeth • Research Grant Results • University of Colorado January 28, 2020January 29, 2020autism, hypersensitivity, neural network, prepulse inhibition, sound, startle

With a $90,000 grant from FRAXA, Dr. McCullagh and Dr. Achem Klug at the University of Colorado investigated whether auditory neural circuits are altered in Fragile X mice. They saw minor differences in these mice compared to B6 (control) mice in several measures of auditory acuity. Fmr1 mice had increased latency to the startle response for almost all conditions compared to B6 mice, suggesting altered timing to acoustic cues. These experiments show that, consistent with patient reports and anatomical/physiological data, the auditory system is altered in a mouse model of FXS, though with some potential compensation leading to a subtle behavioral impact.

Novel Modulators of Potassium Channels to Treat Fragile X

FRAXA Research Foundation 2015 Grants • 2016 Grants • 2017 Grants • Disease Mechanisms • Kaczmarek, Leonard • Research Grant Results • Treatment Targets • Yale University January 2, 2019October 10, 2019Autifony Therapeutics, BK channel, hypersensitivity, ion channel, potassium channels, sound

With funding from FRAXA over 2015-2017, the Yale University team of Leonard Kaczmarek, PhD showed that the firing patterns of auditory neurons in response to repeated stimulation is severely abnormal in Fragile X mice. Based on these results, they are collaborating with the UK-based company Autifony to develop advanced compounds which may reverse these deficits.

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.

Metformin and Aberrant Insulin Signaling in a Fragile X Mouse Model

FRAXA Research Foundation 2017 Grants • 2018 Grants • Current Research Grants • Disease Mechanisms • Gantois, Ilse • McGill University • Sonenberg, Nahum • Treatment Targets November 2, 2018November 20, 2018Alzheimer's, autism, cancer, Fragile X Research Foundation of Canada, metformin

This 2017-2018 grant of $90,000 is funded jointly by FRAXA and the Fragile X Research Foundation of Canada for the first year. A previous FRAXA grant to the Sonenberg lab has led to great interest in the available drug, metformin, as a potential treatment for Fragile X syndrome. FRAXA is currently organizing clinical trials of metformin.

NKCC1 Inhibitor Bumetanide Corrects Synaptic and Circuit Hyperexcitability in Fragile X Mouse Model

FRAXA Research Foundation 2013 Grants • 2014 Grants • 2016 Grants • 2017 Grants • Contractor, Anis • Drug Repurposing • He, Qionger • Northwestern University • Research Grant Results • Treatment Targets September 15, 2018February 7, 2020bumetanide, GABA, hypersensitivity, NIH, seizure

With $258,000 in grants since 2013 from FRAXA Research Foundation, Dr. Anis Contractor and Dr. Qionger He at Northwestern University are exploring the potential of the available drug bumetanide to correct altered GABA signalling in a mouse model of Fragile X syndrome.

Non-Invasive Imaging as a Biomarker for Fragile X Clinical Trials

FRAXA Research Foundation 2017 Grants • 2018 Grants • Biomarkers • Completed Research Grants • Disease Mechanisms • Frick, Andreas • Grokoski, Kamila Castro • Neurocentre Magendie, France • Research Updates September 6, 2018January 18, 2022MRI

FRAXA Research Foundation has renewed Kamila Castro’s 2017 FRAXA Fellowship for a second year. With this $90,000 award, Kamila Castro and Principal Investigator Dr. Andreas Frick are using non-invasive magnetic resonance imaging (MRI) methodology to assess connectivity changes in the brain in Fragile X. If this project is successful, we will have objective outcome measures to evaluate new treatments, both in mice bred to mimic Fragile X and in human patients.

Repurposing Study II: Evaluating Combinations of Drugs to Treat Fragile X

FRAXA Research Foundation 2016 Grants • 2017 Grants • 2018 Grants • Current Research Grants • Drug Repurposing • Healx February 8, 2018July 26, 2018drug combinations, drug repurposing, FDA, FRAXA-DVI, Healx

FRAXA Research Foundation initially partnered with Healx in 2016 to identify existing drugs with potential to treat Fragile X syndrome, using machine learning algorithms and computational biology. The study produced results, and now FRAXA and Healx have launched a new round of studies to evaluate combinations of compounds, including both drugs and natural products.

Fragile X Clinical Trial of AZD7325 in Adults

FRAXA Research Foundation 2017 Grants • 2018 Grants • 2019 Grants • 2020 Grants • 2021 Grants • Biomarkers • Cincinnati Children's Hospital • Clinical • Completed Research Grants • Erickson, Craig • Pending Results • Trials and Studies February 1, 2018January 13, 2022AstraZeneca, AZD7325, GABA, glutamate, NIH

With a $51,000 grant from FRAXA Research Foundation, Dr. Craig Erickson conducting a double-blind, placebo-controlled clinical trial of AZD7325 in adults ages 18-50 with Fragile X syndrome at Cincinnati Children’s Hospital. The compound being studied is an investigational new drug from AstraZeneca that targets GABA (A) receptors.

Lovamix: Clinical Trial of Combined Treatment of Minocycline and Lovastatin in Fragile X Syndrome

FRAXA Research Foundation 2012 Grants • 2015 Grants • 2016 Grants • 2017 Grants • Biomarkers • Clinical • Corbin, Francois • Has Results • Lepage, Jean-Francois • Research Grant Results • Trials and Studies • University of Sherbrooke, Canada October 3, 2017March 17, 2021Fragile X Meeting, lovastatin, minocycline, MRI, Roche

With a $66,714 grant from the FRAXA Research Foundation awarded over 2015-2017, Dr. Francois Corbin at the Universite of Sherbrooke will test the safety and synergistic effects of lovastatin and minocycline in patients with Fragile X syndrome.

Combinatorial Drug Treatment in a Model of Fragile X Syndrome using Novel Biomarkers

FRAXA Research Foundation 2016 Grants • 2017 Grants • Biomarkers • Lovelace, Jonny • Razak, Khaleel • Research Grant Results • Treatment Targets • University of California at Riverside October 3, 2017May 15, 2020drug combinations, EEG, hypersensitivity, matrix metalloproteinase, mGluR5, minocycline, MMP9, sound, Tetra Therapeutics

With a $90,000 grant from FRAXA Research Foundation awarded over 2016-2017, University of California researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, are exploring drug combinations to limit hypersensitivity to sounds in Fragile X mice.

Genome-wide Screen for FMR1 Reactivation in Human FXS Neural Cells

FRAXA Research Foundation 2017 Grants • 2018 Grants • Agency for Science, Technology and Research (A*STAR) • Current Research Grants • Genetic Rescue • Pouladi, Mahmoud • Research Grant Results • Utami, Kagistia October 2, 2017January 13, 2022NIH

Drs. Mahmoud Pouladi and Kagistia Utami at the Agency for Science, Technology and Research (A*STAR) in Singapore have won a $67,500 research grant from FRAXA Research Foundation. Their goal is to reactivate the gene which is silenced in people who have Fragile X syndrome.

MicroRNA Mediated Astroglial GLT1 Dysregulation in Fragile X

FRAXA Research Foundation 2017 Grants • 2018 Grants • Completed Research Grants • Disease Mechanisms • Higashimori, Haruki • Men, Yuqin • Treatment Targets • Tufts University • Yang, Yongjie September 30, 2017October 13, 2020astrocytes, autism, glutamate, Pierce Family Fragile X Foundation

Almost all brain research focuses on neurons – nerve cells. However, the brain has many more glial cells which support, nourish, and protect the neurons. FRAXA Research Foundation awarded a 2017 grant $90,000 to support Dr. Yang’s studies of how changes in glial cells contribute to Fragile X syndrome. This grant is funded by a grant from the Pierce Family Fragile X Foundation.

Correcting Fragile X Syndrome Deficits by Targeting Neonatal PKCepsilon Signaling in the Brain

FRAXA Research Foundation 2017 Grants • 2018 Grants • Banerjee, Probal • College of Staten Island • Completed Research Grants • Disease Mechanisms • Treatment Targets September 30, 2017May 15, 2020

FRAXA Research Foundation has made a 2017 grant of $90,000 to Probal Banerjee, PhD, at the College of Staten Island (CUNY). He is exploring a therapeutic strategy based on correcting abnormalities in the PKCepsilon signaling pathway in Fragile X.

Autophagy is a Novel Therapeutic Target of Impaired Cognition in Fragile X Syndrome

FRAXA Research Foundation 2017 Grants • 2018 Grants • Albert Einstein College of Medicine • Disease Mechanisms • Research Grant Results • Treatment Targets • Zukin, Suzanne September 27, 2017October 10, 2019mTOR, NIH, PSD-95

Dr. Suzanne Zukin, at Albert Einstein College of Medicine, is expert on signaling pathways in the brain and the regulation of synaptic plasticity. With this 2017 grant of $90,000 from FRAXA Research Foundation, she and her team are exploring autophagy, which is how cells clean house, in Fragile X.

Quantitative Assessment of the Serotonin System in a Mouse Model of Fragile X Syndrome

FRAXA Research Foundation 2017 Grants • 2018 Grants • 2019 Grants • Canal, Clinton E. • Completed Research Grants • Disease Mechanisms • Drug Repurposing • Mercer University September 27, 2017March 10, 2021autism, serotonin

FRAXA Research Foundation awarded a grant of $90,000 over two years to Clinton Canal, PhD. Dr. Canal, previously a research assistant professor at Northeastern University, has just launched his own lab at Mercer University in Atlanta, GA, to focus on Fragile X research.

Targeted Transcriptional Reactivation of FMR1 in Fragile X Syndrome Stem Cells

FRAXA Research Foundation 2016 Grants • 2017 Grants • Genetic Rescue • Haenfler, Jill • Research Grant Results • Todd, Peter • University of Michigan September 23, 2017July 29, 2020CRISPR, mRNAs, NIH

With a $90,000 grant from FRAXA Research Foundation awarded in 2016, University of Michigan researcher Peter Todd, MD, PhD, is using CRISPR to selectively turn the Fragile X gene back on in stem cells.

Investigating Gene Reactivation to Treat Fragile X Syndrome

FRAXA Research Foundation 2016 Grants • 2017 Grants • 2018 Grants • Genetic Rescue • Harvard University • Lee, Jeannie • Massachusetts General Hospital • Research Grant Results September 22, 2017March 27, 2019CRISPR, Pierce Family Fragile X Foundation

With a $180,000 grant from FRAXA Research Foundation from 2016-2017, Dr. Jeannie Lee and her team at Harvard are working to reactivate the gene that is silenced in Fragile X syndrome.

Mechanisms of Tolerance to Chronic mGluR5 Inhibition

FRAXA Research Foundation 2015 Grants • 2016 Grants • 2017 Grants • Bear, Mark • Disease Mechanisms • Massachusetts Institute of Technology (MIT) • Osterweil, Emily • Research Grant Results • Senter, Rebecca • Treatment Targets September 19, 2017May 21, 2021AFQ056, drug tolerance, glutamate, lovastatin, mGluR5, NIH, Novartis, Roche

Over the past few years, both Novartis and Roche sponsored large-scale clinical trials of metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulators (NAMs) to treat Fragile X syndrome (FXS). With a $90,000 grant from FRAXA Research Foundation in 2015-2017, Dr. Mark Bear’s team will explore if mGlu5 NAMs dosed chronically causes tolerance, and if so, how it develops and to probe new avenues to prevent or circumvent it.

Prefrontal Cortex Network (PFC) Dynamics in Fragile X Syndrome

FRAXA Research Foundation 2016 Grants • 2017 Grants • Disease Mechanisms • Johnston, Daniel • Research Grant Results • Siegel, Jennifer • Treatment Targets • University of Texas at Austin September 18, 2017October 10, 2019NIH

With a $90,000 grant from FRAXA Research Foundation from 2016-2017, Dr. Daniel Johnston and Dr. Jenni Siegel at the University of Texas at Austin are analyzing pre-frontal cortex (PFC) dysfunction in the Fragile X model. They have preliminary evidence that Fragile X mice are severely impaired in a prefrontal cortex (PFC)-dependent task.

Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X

Theodore Coutilish 2016 Grants • 2017 Grants • 2018 Grants • Biomarkers • Completed Research Grants • Treatment Targets • University of Wisconsin • Westmark, Cara May 23, 2017May 17, 2020Alzheimer's, drug repurposing, EEG, seizure, sleep, sound

FRAXA Research Foundation awarded $122,000 over 2016-2018 to Dr. Cara Westmark at the University of Wisconsin at Madison for studies of sleep disorders in Fragile X syndrome.

A Kinase Assay as a Biomarker for Fragile X Syndrome

Theodore Coutilish 2017 Grants • 2018 Grants • Biomarkers • Completed Research Grants • Kooy, Frank • University of Antwerp, Belgium January 15, 2017May 15, 2020autism, GABA, ganaxolone

With a $90,000 grant from FRAXA Research Foundation over 2017-2018, Dr. Frank Kooy at the University of Antwerp, Belgium, is investigating whether phosphorylation abnormalities are a suitable biomarker for the Fragile X syndrome.

Altered Sleep in Fragile X Syndrome: Basis for a Potential Therapeutic Target

FRAXA Research Foundation 2016 Grants • 2017 Grants • 2018 Grants • Biomarkers • Completed Research Grants • Disease Mechanisms • National Institute of Mental Health • Smith, Carolyn B. • Treatment Targets September 5, 2016May 14, 2020NIH, sleep

With a $90,000 grant from FRAXA Research Foundation over 2016-2018, Dr. Carolyn B. Smith and Dr. Rache Sare at the National Institute of Mental Health investigated the basis of sleep problems in Fragile X syndrome.

Enhancement of NMDA Receptor Signaling for the Treatment of Fragile X Syndrome

Theodore Coutilish 2016 Grants • 2017 Grants • 2018 Grants • Barnes, Stephanie • Completed Research Grants • Osterweil, Emily • Research Updates • Treatment Targets • University of Edinburgh, Scotland August 15, 2016March 26, 2019ERK, glutamate, lovastatin, mGluR, NMDA, seizure

FRAXA Research Foundation funded a 2016-2017 Fellowship for Dr. Stephanie Barnes in the University of Edinburgh lab of Dr. Emily Osterweil. With this $90,000 award, the team is investigating NMDA signaling in fragile X syndrome mice.