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Funded Grants

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Treatment strategies for Autism Spectrum Disorders and Fragile-X Syndrome using mouse models, via translational control modulators

Project Overview

Aberrant control of protein synthesis (also termed translation) leads to pathological conditions like cancer, obesity, memory impairment and has been hypothesized to cause the development of Autism Spectrum Disorders (ASD) and Fragile-X syndrome (FXS). Synaptic connections are regulated by translation, thus impaired translational control is postulated to cause ASD. It is important to develop new therapies for FXS and ASD. To successfully implement new ideas and carry out meaningful clinical trials, it is essential to extensively test any treatment approach in preclinical models, such as mouse models. Similar to humans, FXS/ASD model mice display behavioural deficits and changes at the synapse level. Dr. Sonenbrg and his team are carrying out preclinical studies using mouse models of ASD and FXS, implementing novel genetherapy, optogenetics (controlling individual neurons with light activated rhodopsins) and pharmacological techniques to inhibit translation. In addition, they are examining the effect of FDA approved or in-development inhibitors of translation, which are currently used in the field of cancer. To understand the role of protein synthesis in ASD/FXS, they will also examine the translation of mRNAs in post mortem brain samples and lymphocytes, using RNA sequencing. The proposed research will reveal novel ASD/FXS risk genes and biomarkers due to aberrant protein synthesis. They anticipate that this project will constitute the basis for the development of novel therapeutic avenues in FXS/ASD, through subsequent clinical trials.

Principal Investigator

Nahum Sonenberg , McGill University

Team Members

Jeffrey Mogil, McGill University

Antoine Adamantidis, Adamantidis

Jean-Claude Lacaille, Université de Montréal

Joseph Buxbaum, The Mount Sinai Hospital

Paul Hagerman, University of California, Davis

Randi Hagerman, University of California, Davis

Partners and Donors

Azrieli Foundation

National Bank of Canada

Project Ongoing

Treatment strategies for Autism Spectrum Disorders and Fragile-X Syndrome using mouse models, via translational control modulators

  • Program Type

    Team grants

  • Area of research

    Neurodevelopment

  • Disease Area

    Autism

  • Competition

    Azrieli Neurodevelopment Research Program

  • Province

    Québec

  • Start Date

    2014

  • Total Grant Amount

    $1,235,000

  • Health Canada Contribution

    $617,500

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