WP 1 - Discovery to Translation:

Novel Biomarker and Cognate Therapeutic Targets for Precision Medicine in Heart Failure: Foundation of Innovation

Dr. Peter Liu
  Dr. Peter Liu
Dr. Dunkin Stewart
  Dr. Duncan Stewart

 

Treatments for HF patients with reduced ejection fraction (HFrEF) have improved with newer agents, yet HF with preserved ejection fraction (HFpEF) and acute HF have neither effective treatments, nor disease specific biomarkers that could provide insight into the pathophysiological process or guidance for new therapies.
The TRANSFORM HF team will synergize the expertise and infrastructure across Canada to accelerate HF biomarker discovery, and to translate benefits directly to our patients and national economy. Three complementary and overlapping research themes will be pursued to answer the overarching question: Are new or existing biomarkers capable of precisely identifying underlying mechanisms and temporal stages o HFrEF, HFpEF and acute heart failure, including Indigenous and vulnerable populations?

"Work Package #1", Copyright © 2018 University Health Network. All rights reserved.

"Work Package #1, v.2", Copyright © 2018 University Health Network. All rights reserved.

Biomarker candidates: This Canada-wide HF team has significant experience and proven success in discovering novel biomarkers for HF and bringing them to commercialization, through cutting-edge technology and collaboration. The most robust candidates will be commercialized with our partners. Our network already has a rich portfolio of advanced biomarker candidates for fast-tracked validation.
Candidate biomarkers identified in Theme 1 will be used to specifically phenotype individual patients with HF to establish the dominant contributing mechanisms and enable tailoring of therapies (assessed in WP2), drawing on talents of the existing successful Canadian Vascular Network. There will be a specific focus on diabetes mellitus (DM), an important comorbidity in patients with HF (~ 40% in registries) that is associated with a 5-fold higher incidence of HF than age/sex matched controls, and has an increased prevalence in Indigenous peoples.
We will conduct target validation through deep proteomic tissue analysis with accompanying imaging on human heart samples. Multiple validated targets with human relevance will be subjected to screening for small targeting biologics or small organic molecules using our high throughput screening facility. The Network has a proven track record in developing novel therapeutic candidates. We anticipate, in 5 years’ time, the delivery of 10 novel disease specific biomarker candidates with 2 commercialized for clinical application, and 5 validated therapeutic targets with 2 entering clinical development. The value of our discoveries and findings will require iterative validation in WP2-4.