mRNAs Archives • Fragile X Research - FRAXA Research Foundation

Beneath the Surface of Fragile X Syndrome: Study Sheds Light on What’s Happening in Nerve Cells

University of Rochester Medical Center Kurosaki, Tatsuaki • Maquat, Lynne • Research Grant Results • Research Updates • University of Rochester February 3, 2021February 17, 2021amyloid precursor protein, cancer, drug repurposing, iPS, mRNAs, NIH, Roche, TAT (Trans-Activator of Transcription)

This FRAXA-funded project has turned up some surprising results. At first, it might seem Kurosaki and Maquat have found yet another cellular process which is malfunctioning in Fragile X. But this finding is intimately related to previous findings of abnormal protein synthesis and misregulated transcription in Fragile X. FMRP (the protein lacking in Fragile X syndrome) is involved in chaperoning messenger RNAs within cells to active sites, and in controlling their translation into many different proteins. Some of these proteins are transcription factors, which feed back to the nucleus to control gene expression.

COVID-19 Vaccines Pose Little Risk to Rare Disease Patients, FDA, CDC Say

Fragile X News Today Community February 2, 2021February 3, 2021Adeno-associated virus, amyloid precursor protein, FDA, mRNAs, TAT (Trans-Activator of Transcription)

The two COVID-19 vaccines that recently received emergency approval from the US and other worldwide regulatory agencies are expected to pose little risk to the rare disease community, including to patients with compromised immune systems or those participating in gene therapy studies.

Towards Understanding the Role of FMRP in Human Brain Development Using Brain Organoids

FRAXA Research Foundation Jin, Peng • Seminar Series • Wen, Zhexing December 8, 2020December 8, 2020autism, cancer, DOD, epigenetics, FXPOI, FXTAS, mRNAs, NIH, organoid, TAT (Trans-Activator of Transcription)

Dr. Zhexing Wen and Dr. Peng Jin of the newly funded Fragile X Center of Excellence at Emory University School of Medicine join us in this seminar to present about Understanding the Role of FMRP in Human Brain Development Using Brain Organoids.

Deep Molecular Profiling of Fragile X Mouse and Human Cells

FRAXA Research Foundation 2019 Grants • 2020 Grants • Current Research Grants • Disease Mechanisms • Richter, Joel • Shah, Sneha • University of Massachusetts September 5, 2019October 9, 2020amyloid precursor protein, iPS, mRNAs, Pierce Family Fragile X Foundation, TAT (Trans-Activator of Transcription)

FRAXA Research Foundation has awarded $90,000 to Dr. Joel Richter, Principal Investigator, and Dr. Sneha Shah, Postdoctoral Fellow, at the University of Massachusetts Medical School. They are using human induced pluripotent stem (iPS) cells to analyze gene expression in Fragile X syndrome.

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, autism, BK channel, glutamate, hypersensitivity, ion channel, mGluR, mGluR5, mRNAs, 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.

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

FRAXA Research Foundation 2018 Grants • 2019 Grants • 2020 Grants • Borreca, Antonella • Current Research Grants • Disease Mechanisms • Italian National Institute of Health • Martire, Alberto • Treatment Targets December 11, 2018April 15, 2021AMPA, AMPAkines, BDNF, cyclic AMP, drug tolerance, ERK, glutamate, mGluR, mGluR5, mRNAs, NIH, PAK (p21-activated kinase), sleep, TAT (Trans-Activator of Transcription)

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

Finding Fragile X Biomarkers – From Transcriptomics to Behavior in Patients

FRAXA Research Foundation 2018 Grants • Biomarkers • Carullo, Paulina • Cogram, Patricia • Current Research Grants • Scripps Research Institute • Vanderklish, Peter November 6, 2018January 3, 2019amyloid precursor protein, EEG, ERK, FRAXA-DVI, mRNAs

With this $20,000 award from FRAXA Research Foundation, Dr. Vanderklish and collaborators at Scripps Research Institute, the University of Chile, and the FLENI Institute in Argentina are analyzing patterns in gene expression in blood cells of patients with Fragile X syndrome. They are using “transcriptomics” which can produce a time-sensitive signature of an individual person. This is the first time that all these different levels of study – from transcriptomics to behavior – have been done for individual patients with Fragile X.

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, 2018amyloid precursor protein, mRNAs, 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.

How Promising is CRISPR for Fragile X?

Dave Bjork Research Updates • Todd, Peter August 14, 2018January 20, 2021amyloid precursor protein, CRISPR, FXTAS, mGluR, mRNAs, NIH, PSD-95, Roche, TAT (Trans-Activator of Transcription)

Peter Todd, MD, PhD, Assistant Professor in the Department of Neurology in the University of Michigan Medical School, was recently awarded a FRAXA Research Grant for gene reactivation with the use of CRISPR. In this interview he tells us about CRISPR in Fragile X research, how realistic is it that it could turn the Fragile X gene back on, and if it can really be a cure for Fragile X.

In Their Own Words: Reports From the International Fragile X Workshop

FRAXA Research Foundation Cogram, Patricia • Contractor, Anis • Events Recap • Kooy, Frank • Lee, Jeannie • McGill University • Moine, Herve • Razak, Khaleel • Research Updates • Smith, Carolyn B. • Sonenberg, Nahum • Todd, Peter • Vanderklish, Peter October 29, 2017December 26, 2019amygdala, amyloid precursor protein, autism, bumetanide, DgkK, drug repurposing, drug tolerance, EEG, ERK, FDA, Fragile X Meeting, GABA, ganaxolone, glutamate, hyperexcitability, hypersensitivity, metformin, mGluR, mGluR5, minocycline, mRNAs, NIH, Rett syndrome, seizure, sleep, sound, TAT (Trans-Activator of Transcription)

The 18th International Fragile X and Related Neurodevelopmental Disorders Workshop in Quebec, Canada, was a great success, featuring Fragile X much more heavily than any previous meeting in this series! We asked our speakers to summarize their work in their own words, with brief updates from researchers investigating Fragile X.

18th International Fragile X and Related Neurodevelopmental Disorders Workshop, Quebec, Canada

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, 2020amyloid precursor protein, CRISPR, 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.

Fragile X Nervous (System) Breakdown

Theodore Coutilish Disease Mechanisms • Research Updates March 21, 2017June 14, 2018amyloid precursor protein, drug repurposing, mRNAs, Roche, TAT (Trans-Activator of Transcription)

“The occurrence and development of events by chance in a happy or beneficial way.” That’s how Lynne E. Maquat, PhD, describes the process of how her research extended to Fragile X syndrome to better understand it and ultimately find advanced treatments.

Function of FMRP and Test of a Novel Therapeutic Approach in a Fragile X Mouse Model

FRAXA Research Foundation 2015 Grants • 2016 Grants • Disease Mechanisms • Geoffroy, Andrea • IGBMC. France • Moine, Herve • Research Grant Results September 16, 2016March 28, 2019DgkK, mRNAs

With a 2015-2016 $90,000 grant from FRAXA Research Foundation, Dr. Herve Moine and Dr. Andrea Geoffroy aim to uncover the exact role of FMRP and to test a novel possible means to correct for FMRP absence in the mouse model of Fragile X syndrome.

Fragile X Mutant Mouse Facility

FRAXA Research Foundation 2006-2010 Grants • 2011 Grants • 2012 Grants • 2014 Grants • 2015 Grants • 2016 Grants • Baylor College of Medicine • Disease Mechanisms • Nelson, David • Resources September 10, 2016February 20, 2018amyloid precursor protein, FXTAS, mRNAs, TAT (Trans-Activator of Transcription)

With $375,000 in grants from the FRAXA Research Foundation since 2009, Dr. David Nelson has developed an impressive array of advanced mouse models of Fragile X, at Baylor College of Medicine. These models are available to investigators worldwide on request. This resource has been essential for a broad, rapid distribution of Fragile X and related gene mouse models and has increased the pace of Fragile X research.

Repurposing Drugs to Dampen Hyperactive Nonsense-Mediated Decay in Fragile X Syndrome

FRAXA Research Foundation 2015 Grants • 2016 Grants • Disease Mechanisms • Drug Repurposing • Kurosaki, Tatsuaki • Maquat, Lynne • Research Grant Results • Treatment Targets • University of Rochester September 8, 2016February 11, 2021amyloid precursor protein, Boston Bruins Foundation, mRNAs, NIH, Roche, TAT (Trans-Activator of Transcription)

With a $90,000 grant from the FRAXA Research Foundation, Dr. Lynne Maquat and Dr. Tatsuaki Kurosaki will investigate nonsense-mediated mRNA decay (NMD) in Fragile X. NMD is a “housekeeping” process that cells use to prevent faulty proteins from being made. But there is too much of it in Fragile X syndrome. There are already available drugs that suppress NMD – including caffeine.

Boston Bruins Grant Funds New Fragile X Research

FRAXA Research Foundation FRAXA Updates May 28, 2015December 26, 2019amyloid precursor protein, autism, Boston Bruins Foundation, drug repurposing, iPS, mRNAs, Roche, TAT (Trans-Activator of Transcription)

Bruins Foundation Executive Director Bob Sweeney pledging a $90,000 donation to FRAXA Research today at Shared Living Collaborative’s Gateway Farm in Merrimac, MA. The award will enable the organization to fund an entirely new research project aimed at developing new treatments for Fragile X, a genetic syndrome that is the most common inherited cause of autism.

Bruins $90,000 donation to FRAXA for Fragile X research grant

FRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome

FRAXA Research Foundation 2015 Grants • 2016 Grants • Disease Mechanisms • Drug Repurposing • McGill University • Research Grant Results • Sonenberg, Nahum • Treatment Targets April 8, 2015May 15, 2020AMPK, amyloid precursor protein, FDA, metformin, mRNAs, mTOR

Mis-regulation of activity-dependent protein synthesis is one of the major cellular abnormalities found in Fragile X. Upstream neuronal signaling regulates a large cluster of enzymes called the mTORC1 complex, which in turn regulates protein synthesis. This complex is also controlled by cellular energy levels via the metabolic sensor AMP-activated Protein Kinase (AMPK). AMPK is a highly conserved kinase that is activated under conditions of energy stress, when intracellular ATP levels decline and intracellular AMP increases.

Inhibitors of STEP as a Novel Treatment of Fragile X Syndrome

FRAXA Research Foundation 2006-2010 Grants • 2011 Grants • 2014 Grants • 2015 Grants • Disease Mechanisms • Lombroso, Paul • Research Grant Results • Treatment Targets • Yale University February 26, 2015May 17, 2020AMPA, AMPAkines, amyloid precursor protein, autism, glutamate, LTD (Long-term depression), mRNAs, NIH, seizure, STEP (STriatal-Enriched protein tyrosine Phosphatase), TAT (Trans-Activator of Transcription)

With a $349,000 grant from FRAXA Research Foundation from 2008-2015, Dr. Paul Lombroso and his team at Yale University researched if inhibiting STEP could reduce behavioral abnormalities in Fragile X syndrome. Results published.

Paul Lombroso, PhD, Yale University, FRAXA Investigator

Molecular Mechanisms of Cytoskeletal Regulation by FMRP

FRAXA Research Foundation 2015 Grants • Completed Research Grants • Cornell University • Disease Mechanisms • Jaffrey, Samie • Treatment Targets January 9, 2015December 4, 2019amyloid precursor protein, mRNAs

With a 2-year, $120,000 grant from FRAXA Research Foundation in 2015, Dr. Samie Jaffrey from Weill Medical College of Cornell University will research the connection between FMR1, RhoA, and dendritic spine abnormalities.

Functional Interplay Between FMRP and CDK5 Signaling

FRAXA Research Foundation 2011 Grants • 2012 Grants • 2013 Grants • 2014 Grants • Biomarkers • Disease Mechanisms • Emory University • Feng, Yue • Li, Wenqi • Research Grant Results • Treatment Targets September 13, 2014June 29, 2020Alzheimer's, amyloid precursor protein, CDK5, GABA, MAP1b, mGluR, mGluR5, mRNAs, NIH

With a $180,000 grant from the FRAXA Research Foundation over 2011-2014, Dr. Yue Feng and Dr. Wenqi Li at Emory University will study CDK5 pathway function and regulation in an effort to break down whether and how CDK5 signaling is affected by the loss of the Fragile X protein, FMRP, in the Fragile X mouse model.

Scientists Uncover Trigger for Fragile X Syndrome

FRAXA Research Foundation Cornell University • Jaffrey, Samie • Research Updates February 27, 2014December 26, 2019amyloid precursor protein, autism, mRNAs, neural stem cells, NIH, TAT (Trans-Activator of Transcription)

A new study led by Weill Cornell Medical College scientists shows that Fragile X syndrome occurs because of a mechanism that shuts off the gene associated with the disease. The findings, published today in Science, also show that a compound that blocks this silencing mechanism can prevent Fragile X syndrome – suggesting a similar therapy may be possible for 20 other diseases that range from mental retardation to multisystem failure.

Samie Jaffrey, PhD, at Weill Medical College of Cornell University, FRAXA research grant

Small Molecules To Target r(CGG) Expansions to Treat Fragile X Syndrome

FRAXA Research Foundation 2012 Grants • 2013 Grants • Disney, Matthew • FRAXA Research Grants • Genetic Rescue • Research Grant Results • Treatment Targets • Yang, Wang-Yong January 24, 2014July 29, 2020amyloid precursor protein, FXTAS, mRNAs, NIH, RNAi

With a 2-year, $90,000 grant from FRAXA Research Foundation, Dr.’s Matthew Disney and Wang-Yong Yang worked to correct the underlying problem in Fragile X: the silencing of the Fragile X gene (FMR1) and the resulting lack of FMRP (Fragile X Mental Retardation Protein). Their approach was to use novel small molecules to target the abnormal CGG repeats before the FMR1 gene.

Fragile X Syndrome Protein Linked to Breast Cancer Progression

FRAXA Research Foundation Bagni, Claudia • Research Updates September 18, 2013December 26, 2019cancer, mRNAs

Claudia Bagni (VIB/KU Leuven, Belgium, and the University of Rome, Italy) and colleagues have identified the way Fragile X Mental Retardation Protein or FMRP contributes to the progression of breast cancer. The researchers demonstrated that FMRP acts as a master switch controlling the levels of several proteins involved in different stages of aggressive breast cancer, including the invasion of cancer cells into blood vessels and the spread of these cancer cells to other tissues forming metastasis.

Ab-Mediated Translation in Fragile X Syndrome

FRAXA Research Foundation 2011 Grants • 2012 Grants • Biomarkers • Research Grant Results • Treatment Targets • University of Wisconsin • Westmark, Cara September 13, 2012January 29, 2021Alzheimer's, amyloid precursor protein, LTD (Long-term depression), mGluR, mGluR5, mRNAs, NIH, seizure

With a $120,000 grant from FRAXA Research Foundation during 2011-2012, Dr. Cara Westmark at the University of Wisconsin explored the role of AbPP as a potential treatment option for fragile X. AbPP produces b-amyloid which is over-expressed in Alzheimer’s disease (AD) and Down syndrome.

Fragile X Researcher, Cara Westmark, PhD

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.

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