{"id":"https://openalex.org/G3449525129","display_name":"Pharmacological correction of dysregulated glutamatergic signaling in the Fragile X brain","description":"Fragile-X syndrome (FXS) is a neurodevelopmental disorder that is the most common single-gene cause of autism and inherited intellectual disability. In Canada, it affects 1 in 4,000 boys and 1 in 6,000 girls irrespective of race or ethnic background. FXS results from disrupted expression of the Fragile X Messenger Ribonucleoprotein (FMRP), a RNA binding protein essential for normal brain development. Despite this level of understanding, there is still no cure or specific treatment for FXS. Consequently, any future advances will rely on a better understanding of how the absence of FMRP leads to deficits in the FXS brain. In this grant application, we identify a homeostatic regulatory mechanism that regulates the activity of nerve cells and local blood vessels in a brain region called the cerebellum. We propose that this homeostatic mechanism is found throughout the brain where it maintains the balance between excitatory and inhibitory (E/I) signaling. Importantly, the coupling between neuronal activity and local vessel regulation is lost in a mouse model of FXS but can be rescued with a novel combination therapy of repurposed drugs that boost the deficits in several signaling pathways. The benefit of the proposed project is that it aims to uncover the widespread occurrence of a potentially important defect in FXS that can be corrected by pharmacological treatment.","funder_award_id":"190276_1","funder":{"id":"https://openalex.org/F4320334506","display_name":"Canadian Institutes of Health Research","doi":"https://doi.org/10.13039/501100000024"},"funded_outputs":["https://openalex.org/W7134119693"],"funded_outputs_count":1,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":1067176.0,"currency":"CAD","amount_usd":794662.44,"amount_usd_basis":"daily_rate","recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"Project Grant","start_date":"2023-10-01","end_date":"2028-09-30","start_year":2023,"end_year":2028,"landing_page_url":"https://open.canada.ca/data/en/dataset/49edb1d7-5cb4-4fa7-897c-515d1aad5da3","doi":null,"provenance":"cihr_opendata","lead_investigator":{"given_name":"Derek","family_name":"Bowie","orcid":null,"role_start":"2023-10-01","affiliation":{"name":"McGill University","country":"Canada","ids":null},"author":{"id":"https://openalex.org/A5008112491","display_name":"Derek Bowie","orcid":"https://orcid.org/0000-0001-9491-8768"},"institutions":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}]},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G3449525129","primary_topic":{"id":"https://openalex.org/T11772","display_name":"Genetics and Neurodevelopmental Disorders","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11772","display_name":"Genetics and Neurodevelopmental Disorders","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.0001,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10106","display_name":"Autism Spectrum Disorder Research","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2805","display_name":"Cognitive Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/fragile-x-syndrome","display_name":"fragile X syndrome","score":0.997},{"id":"https://openalex.org/keywords/fmrp","display_name":"FMRP","score":0.967},{"id":"https://openalex.org/keywords/glutamatergic-signaling","display_name":"glutamatergic signaling","score":0.97},{"id":"https://openalex.org/keywords/excitation-inhibition-balance","display_name":"excitation-inhibition balance","score":0.894},{"id":"https://openalex.org/keywords/cerebellum","display_name":"cerebellum","score":0.981},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.747},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.745},{"id":"https://openalex.org/keywords/neurodevelopmental-disorders","display_name":"neurodevelopmental disorders","score":0.627},{"id":"https://openalex.org/keywords/autism-spectrum-disorder","display_name":"autism spectrum disorder","score":0.477},{"id":"https://openalex.org/keywords/intellectual-disability","display_name":"intellectual disability","score":0.901}],"sustainable_development_goals":[{"score":0.9537,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"institution_awarded":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}],"updated_date":"2026-11-13T03:01:57.000Z","created_date":"2026-07-13T04:27:47.000Z"}