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Crosstalk between immune response and metabolic signaling: targeting leptin/AMPK axis to restore metabolic homeostasis in ALS

Principal Investigator:
  • Jasna Kriz, Université Laval
Team Members:
  • Nicolas Dupré, CRCHUQ-Enfant-Jesus, University Laval
  • Angela Genge, McGill University

Project Overview

Increased metabolism (hypermetabolism) is a characteristic often associated with more aggressive, faster progressing cases of ALS. Recently, after studying blood plasma samples from people with more rapidly progressing disease, Dr. Jasna Kriz discovered that fast progressing individuals often have decreased levels of a hormone called leptin, and increased levels of specific immune markers called CCL16 and sTNF-RII.

With this grant, Dr. Kriz and her team will examine whether these specific blood markers are directly linked to more aggressive forms of disease and therefore whether they may be able to serve as predictors of disease progression. Using ALS cell and mice models, they will also explore whether manipulating the levels of these markers could help to mediate disease progression. Finally, it is hypothesized that the altered leptin levels result from overactivation of an enzyme called AMPK, and the team will determine if targeting this enzyme represents a potential therapeutic strategy for ALS.

This work will shed light on potential biomarkers of ALS disease progression and help researchers to understand whether correcting this abnormal signature can have beneficial effects on slowing disease course.