matrix metalloproteinase Archives • Fragile X Research

Mechanisms and Biomarkers of Sensory Hypersensitivity in the fmr1 Knockout Mouse

FRAXA Research Foundation Binder, Devin • Razak, Khaleel • Research Updates • Seminar Series August 27, 2020August 27, 2020astrocytes, DoD, drug repurposing, EEG, glutamate, Healx, hypersensitivity, matrix metalloproteinase, NIH, seizure, sound

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.

Clinical Trial of Metformin for Fragile X Syndrome

FRAXA Research Foundation 2018 Grants • 2019 Grants • 2020 Grants • Clinical • Current Research Grants • Lepage, Jean-Francois • Pending Results • Trials and Studies • University of Sherbrooke, Canada May 24, 2019February 9, 2021EEG, ERK, matrix metalloproteinase, metformin, MMP9

Metformin is commonly prescribed to control high blood sugar in type 2 diabetes. With a $50,000 grant from FRAXA Research Foundation, Dr. Artuela Çaku and Dr. Francois LePage are conducting an open-label clinical trial of metformin for children and adults with Fragile X syndrome, at the University of Sherbrooke in Canada.

Understanding and Reversing Hypersensitivity to Sounds in Fragile X Syndrome

FRAXA Research Foundation 2018 Grants • 2019 Grants • 2020 Grants • Binder, Devin • Current Research Grants • Ethell, Iryna • Pirbhoy, Patricia • Treatment Targets • University of California at Riverside June 20, 2018May 15, 2020CBD, EEG, endocannabinoid, hyperexcitability, hypersensitivity, matrix metalloproteinase, minocycline, MMP9, sound

With a $90,000 grant from FRAXA Research Foundation over 2018-2019, Drs. Devin Binder, Iryna Ethell, and Patricia Pirbhoy at the University of California at Riverside aim to understand – and reverse – hypersensitivity to sound in Fragile X syndrome.

Devon Binder, PhD; Iryna Ethell, PhD, Patricia Pirbhoy, PhD, at UC Riverside School of Medicine

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.

Funding opportunities - FRAXA investigators

Metformin, Diabetes Drug, Potential Fragile X Treatment

Theodore Coutilish Drug Repurposing • McGill University • Research Updates • Sonenberg, Nahum May 18, 2017January 9, 2019autism, cancer, matrix metalloproteinase, metformin, MMP9, prepulse inhibition, Roche, sleep

“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.

Nahum Sonenberg, PhD, 2017 Fragile X Research Grant

Repurposing Available Drugs to Treat Fragile X Syndrome – FRAXA Initiatives

Michael Tranfaglia, MD Drug Repurposing • Research Updates February 10, 2017December 26, 2019arbaclofen, autism, baclofen, drug repurposing, FRAXA-DVI, glutamate, GSK3, Healx, hypersensitivity, lithium, lovastatin, MAP1b, matrix metalloproteinase, metformin, mGluR, minocycline, NIH

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.

Fragile X Syndrome Treatment Target: MMP-9

Michael Tranfaglia, MD Ethell, Iryna • Research Updates • University of California at Riverside July 24, 2014December 13, 2019matrix metalloproteinase, minocycline, MMP9, mTOR

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.)

Iryna Ethell UC Riverside, FRAXA researcher

Matrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome

FRAXA Research Foundation 2012 Grants • 2013 Grants • Broadie, Kendal • Disease Mechanisms • Drug Repurposing • Gatto, Cheryl • Research Grant Results • Treatment Targets • Vanderbilt University September 2, 2013May 21, 2020fruit fly, matrix metalloproteinase, minocycline, NIH, prepulse inhibition, RNAi

With a $157,000 grant from the FRAXA Research Foundation in 2012-2013, Dr. Kendal Broadie and Dr. Cheryl Gatto worked to define the distinct but also overlapping roles for MMP-1 and MMP-2 in synaptic structural and functional development. In drug studies with Fragile X fruit flies, they will be testing a range of MMPIs in drug treatments to compare effectiveness during development and at maturity, in order to define the contributions of FXS developmental impairments and adult recovery/plasticity.

Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X

FRAXA Research Foundation 2012 Grants • 2013 Grants • Ethell, Iryna • Razak, Khaleel • Research Grant Results • Treatment Targets • University of California at Riverside June 2, 2013November 12, 2019autism, hyperexcitability, hypersensitivity, matrix metalloproteinase, minocycline, NIH, sound, startle

With $135,000 in grants from FRAXA Research Foundation over several years, Dr. Khaleel Razak and Dr. Iryna Ethell explored robust biomarkers relevant to the FXS and the efficacy of minocycline treatment.

Encouraging Results from First Trial of Minocycline in Fragile X

FRAXA Research Foundation 2006-2010 Grants • Clinical • Has Results • Paribello Carlo • Research Grant Results • Surrey Place Centre Toronto • Trials and Studies October 10, 2010April 27, 2020Fragile X Research Foundation of Canada, matrix metalloproteinase, mGluR5, minocycline, MMP9, Tetra Therapeutics

With a $40,000 grant from FRAXA, Dr. Carlo Paribello and his team at the Surrey Place Centre Fragile X clinic in Toronto, Ontario, ran an open label trial to see if minocycline can improve learning and reduce anxiety and behavioral problems in people with Fragile X. Twenty participants between the ages of 13 and 35 years took minocycline for two months.

Role of Matrix Metalloproteinases (MMP-9) in Fragile X

FRAXA Research Foundation 2006-2010 Grants • Bilousova, Tina • Disease Mechanisms • Ethell, Iryna • Research Grant Results • Treatment Targets • University of California at Riverside February 2, 2009March 28, 2019autism, glutamate, matrix metalloproteinase, mGluR, minocycline, MMP9, Rett syndrome, Tetra Therapeutics

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.

Iryna Ethell, PhD, at University of California

Researchers Propose Minocycline to Treat Fragile X

Katie Clapp Research Updates October 4, 2008December 12, 2019Fragile X Research Foundation of Canada, matrix metalloproteinase, minocycline

A University of California Riverside team of scientists has found that an available drug called minocycline, used widely to treat acne and skin infections, might also be used to treat Fragile X. The study’s findings have already led to the approval of a FRAXA-funded clinical trial in Toronto, Canada, that will test minocycline in patients with Fragile X.