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Examining the role of KCC2 in maintaining the balance between excitation and inhibition in ALS

Project Overview

Each muscle in the body receives electrical signals through motor neurons that will stimulate it to contract. Other specialized neurons inhibit these signals, allowing muscles to relax. When this inhibitory process does not occur, motor neurons become overexcited, a hallmark feature of ALS before symptoms appear, particularly in the upper motor neurons of the motor cortex.

In this project, Dr. Sahara Khademullah will establish whether a protein called KCC2 (potassium chloride cotransporter 2), which is found to be lower in people with sporadic ALS than in people without the disease, is a viable target to prevent or stop ALS progression. This research builds on two projects previously funded by ALS Canada (one in partnership with Brain Canada Foundation) that explored how enhancing the inhibitory response in the motor cortex may be protective in ALS. Dr. Khademullah will determine the extent of KCC2 deficits and when they occur in mice that have been genetically altered to mimic aspects of human ALS. Using newly-developed and non-invasive technology, she will also measure a readout of KCC2 loss in real time as the disease progresses in mice.

Khademullah will also determine whether KCC2 in cerebrospinal fluid (CSF) could be a reliable biomarker for ALS. She will collect CSF from ALS mice before they have developed symptoms and throughout disease onset and progression and compare the results to CSF from normal mice. Learning when KCC2 deficits occur may provide essential clues about optimal timing for treatment. Finally, Dr. Khademullah will test whether an experimental drug developed by Dr. De Koninck called CLP290 can retain or recover the ability to inhibit motor neurons by restoring KCC2 levels, which may slow or even stop disease progression. Overall, this research may identify KCC2 as a viable target for future drug development and a reliable biomarker to speed diagnosis and measure responses to new treatment options in clinical trials.

Principal Investigator

Sahara Khademullah , Université Laval

Partners and Donors

ALS Society of Canada

La Fondation Vincent Bourque

Project Ongoing

Examining the role of KCC2 in maintaining the balance between excitation and inhibition in ALS

  • Grant Type

    Capacity building grants

  • Area of research

    Neurodegeneration

  • Disease Area

    ALS

  • Competition

    ALS Canada – Brain Canada Trainee Program 2018

  • Province

    Québec

  • Start Date

    2018

  • Total Grant Amount

    $165,000

  • Health Canada Contribution

    $82,500

Contact Us

1200 McGill College Avenue
Suite 1600, Montreal, Quebec
H3B 4G7

+1 (514) 989-2989 info@braincanada.ca

Please note all online donations will receive an electronic tax receipt, issued by Brain Canada Foundation.

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Territorial acknowledgement

The offices of Brain Canada Foundation are located on the traditional, ancestral territory of the Kanien'kehá:ka Peoples, a place which has long served as a site of meeting and exchange amongst nations. We honour and pay respect to elders past, present and emerging, and dedicate ourselves to moving forward in the spirit of partnership, collaboration, and reconciliation. In our work, we focus our efforts on the Truth and Reconciliation Commission’s Calls to Action, particularly those that pertain to improving health for Indigenous Peoples and that focus on advancing our own learning on Indigenous issues.

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  • About
    • What We Do
    • EDI Action Plan
    • Leadership
    • Team
    • Annual Report
    • Publications
    • Careers
  • Brain Conditions
    • One Brain
    • ALS
    • Autism (ASD)
    • Brain Cancer
    • Brain Injury
    • Dementia
    • Epilepsy
    • Mental Illness
    • Multiple Sclerosis
    • Parkinson’s
    • Stroke
    • More
  • Research
    • Programs
    • Funding Opportunities
    • Program Partners
    • Announcements
  • Impact
    • Research Impact Stories
    • Equity, Diversity and Inclusion
    • Brain Health in Indigenous Communities
    • Women’s Brain Health
    • Mind Over Matter
  • How You Can Help
    • Ways to Give
    • Start a Fundraiser
    • Workplace Giving
    • The Great Minds
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