Dr. Xinyu Zhao of the Waisman Center and Department of Neuroscience at University of Wisconsin-Madison joins us in this seminar to present Interrogate the Functions of FMRP in Brain Development Using Stem Cells.
In this Fragile X research webinar we hear from Devin K. Binder, MD, PhD, Professor, University of California at Riverside Medical School and Khaleel Razak, PhD, Professor, University of California at Riverside as they present about Mechanisms and Biomarkers of Sensory Hypersensitivity in the fmr1 Knockout Mouse.
FRAXA-funded open-label trial found that metformin led to increased GABA-mediated cortical inhibition, suggesting metformin modulates core Fragile X pathways.
This FRAXA grant studied why people with Fragile X are overly sensitive to sound and tested drug strategies to calm the brain’s overactive auditory circuits.
University of California researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, explored drug combinations to limit hypersensitivity to sounds in Fragile X mice.
“We treated mice with metformin and corrected all the core Fragile X deficits. We are optimistic about using metformin in human clinical trials. This is a generic drug with few side effects” says Nahum Sonenberg, PhD, James McGill Professor, Department of Biochemistry, McGill Cancer Center, McGill University.
FRAXA Research Foundation was founded in 1994 to fund biomedical research aimed at finding a cure for Fragile X syndrome and, ultimately, autism. We prioritize translational research with the potential to lead to improved treatments for Fragile X in the near term. Our early efforts involved supporting a great deal of basic neuroscience to understand the cause of Fragile X. By 1996, these efforts had already begun to yield results useful for drug repurposing. To date, FRAXA has funded well over $25 million in research, with over $3 million of that for repurposing existing drugs for Fragile X.
Dr. Ethell was awarded FRAXA Research Foundation funding from 2008-2011 and 2012-present. This latest work shows that human Fragile X tissues have elevated levels of the extracellular enzyme MMP-9, as well as an increase in the active fraction of that protein (like most enzymes, MMP-9 can exist in an inactive form which can be switched on rapidly; this kind of regulation is important in most biological pathways.)
Dr. Broadie showed that MMP enzymes disrupt synapse development in Fragile X. MMP inhibitors (e.g. minocycline) improved connectivity and behavior in fruit flies.
A clinical trial of minocycline in children with Fragile X found significantly better global improvement vs. placebo, supporting its safety and potential.
With a $220,000 grant from FRAXA Research Foundation over 3 years, Dr. Iryna Ethell from the University of California at Riverside studied the regulation of dendritic structure by matrix metalloproteinases and other extracellular signaling pathways. This work identified a major treatment strategy for Fragile X with the available MMP-9 inhibitor, minocycline.
This team has found that an available drug called minocycline, an inhibitor of mmp9, might also be used to treat Fragile X. Clinical trials later tested this.
