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Funded Grants

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Preclinical and clinical studies with withanolides: Therapeutic effects, molecular signatures and biomarkers

Project Overview

One of the hallmarks of ALS is the presence of abnormal clumps inside motor neurons that contain various substances which include, in the majority of cases, something called TAR DNA–binding protein 43 (TDP-43). As a result, understanding the mechanisms by which TDP-43 may influence the disease may have a tremendous impact on our ability to treat ALS. Previous research by Dr. Jean-Pierre Julien and his team showed that TDP-43 interacted with something called nuclear factor- κB (NF-κB), which is master regulator of inflammation, a process that has been implicated in the disease mechanism of ALS. Further work revealed that treatment of ALS model mice in the laboratory with an NF-κB inhibitor called Withaferin A, reduced disease symptoms and neuroinflammation. Furthermore, the plant Withania somnifera (Ashwagandha), from which Withaferin A is derived, also had positive effects in ALS model mice when fed to them. As a result, Dr. Julien started collaboration with ImStar Therapeutics, Inc. to create new drugs that mimic Withaferin A, but with enhanced characteristics to be used for treatment of ALS. This work has resulted in a compound called IMS-088 and this Hudson Grant will fund the preclinical (laboratory) studies to investigate its use as a possible ALS therapy. Using unique ALS mouse models that are termed RiboTag, which will allow instant monitoring of specific cells that are important to the disease as the symptoms progress, Dr. Julien’s team will determine not only if IMS-088 works to slow down the progression of the disease, but will also determine if there are specific biological markers (biomarkers) that can be used to monitor the effectiveness of substance in humans should it succeed in reaching clinical trial. One of the targets they will monitor in the mice is specific blood cells. If IMS-088 treatment effectiveness can be detected, it is possible that a simple blood test might yield all of the information needed to determine if the drug is doing its proper anti-inflammatory job in humans during clinical trial.

Principal Investigator

Jean-Pierre Julien , Université Laval

Team Members

Jasna Kriz, Université Laval

Angela Genge, McGill University

Partners and Donors

ALS Society of Canada

Project Ongoing

Preclinical and clinical studies with withanolides: Therapeutic effects, molecular signatures and biomarkers

  • Program Type

    Team grants

  • Area of research

    Neurodegeneration

  • Disease Area

    ALS

  • Competition

    ALS Arthur J. Hudson Translational Team Grant

  • Province

    Québec

  • Start Date

    2015

  • Total Grant Amount

    $2,478,763

  • Health Canada Contribution

    $1,239,381

Contact Us

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

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

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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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