matrix metalloproteinase Archives • Fragile X Research

Recruiting: Clinical Trial of Metformin for Fragile X Syndrome

FRAXA Research Foundation 2018 Grants • 2019 Grants • Clinical • Clinical Trials • Current Research Grants • Lepage, Jean-Francois • Recruiting • University of Sherbrooke, Canada May 24, 2019June 25, 2019EEG, 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 • Binder, Devin • Current Research Grants • Ethell, Iryna • Pirbhoy, Patricia • Treatment Targets • University of California at Riverside June 20, 2018June 20, 2018CBD, 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.

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

FRAXA Research Foundation 2016 Grants • 2017 Grants • Biomarkers • Current Research Grants • Lovelace, Jonny • Razak, Khaleel • Treatment Targets • University of California at Riverside October 3, 2017March 22, 2018EEG, hypersensitivity, matrix metalloproteinase, mGluR5, minocycline, MMP9, sound

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.

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, 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.

Repurposing Available Drugs to Treat Fragile X Syndrome – FRAXA Initiatives

Michael Tranfaglia, MD Drug Repurposing • Research Updates February 10, 2017July 26, 2018arbaclofen, autism, baclofen, FRAXA-DVI, glutamate, GSK3, Healx, hypersensitivity, lithium, lovastatin, MAP1b, matrix metalloproteinase, metformin, mGluR, minocycline

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. Here are some examples of FRAXA-funded work on repurposing available drugs for Fragile X syndrome: Lithium In the mid-1990s, the Greenough lab at the University of Illinois discovered that FMRP, the protein missing in Fragile X, is rapidly translated in dendrites in response to stimulation of glutamate receptors. FRAXA funded preclinical validation of this discovery in theRead more

Fragile X Syndrome Treatment Target: MMP-9

Michael Tranfaglia, MD Ethell, Iryna • Research Updates • University of California at Riverside July 24, 2014July 9, 2018matrix metalloproteinase, minocycline, MMP9, mTOR

A major article from the Ethell lab at UC Riverside has shown the therapeutic potential of drugs that inhibit the enzyme MMP-9. A nice lay description of the new paper is here and the abstract of the article is here. 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.) The Ethell lab also showed that genetic reduction of MMP-9 rescues most Fragile X phenotypes in the mouse model. Previous work had shown that inhibition of MMP-9 with minocycline also had similar effects, but minocycline has many different actions. These experiments demonstrate conclusively that MMP-9 inhibition is the activeRead more

Matrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome

FRAXA Research Foundation 2012 Grants • 2013 Grants • Broadie, Kendal • Completed Research Grant • Disease Mechanisms • Drug Repurposing • Gatto, Cheryl • Treatment Targets • Vanderbilt University September 2, 2013April 25, 2018fruit fly, matrix metalloproteinase, minocycline, RNAi

With a $157,000 grant from the FRAXA Research Foundation in 201202013, 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 • Has Results • Razak, Khaleel • Treatment Targets • University of California at Riverside June 2, 2013November 12, 2019autism, hyperexcitability, hypersensitivity, matrix metalloproteinase, minocycline, 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.

Clinical Trial of Minocycline Promising

Katie Clapp Research Updates October 12, 2010December 12, 2019matrix metalloproteinase, minocycline

Results of the first clinical trial of Minocycline in Fragile X patients has been published, and they suggest that this medication can Improve challenging behaviors commonly seen in Fragile X. Twenty males and females with Fragile X, ages 13-32, participated in this open-label add-on trial at the Fragile X clinic in Toronto, Canada. Dr. Carlo Paribello, himself father of two boys with Fragile X, led the trial which was funded by FRAXA.

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

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

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.

Researchers Propose Minocycline to Treat Fragile X

Katie Clapp Research Updates October 4, 2008December 12, 2019autism, Fragile 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.

Pilot Trial of Minocycline in Fragile X

FRAXA Research Foundation 2006-2010 Grants • Clinical • Has Results • Paribello Carlo • Surrey Place Centre Toronto July 9, 2008December 12, 2019autism, Fragile X Research Foundation of Canada, matrix metalloproteinase, mGluR5, minocycline, MMP9

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.