RICHARD HOGE

Quantitative O2 MRI: a new window on mitochondrial dysfunction in Alzheimer’s Disease

 

Competition: FOCUS Program 2012
Funding: $1,500,000 / 3 years
Beginning: September 2012

Dr Hoge’s team has developed a new MRI-based method (QUO2 MRI) for non-invasive imaging of oxidative metabolism in the human brain. The objective of this project is therefore to optimize the method in Alzheimer’s disease patients to characterize mitochondrial dysfunction hypothesized to be a contributing factor in the onset of AD. .

Alzheimer’s disease (AD) is a progressive, debilitating neurodegenerative condition that can affect individuals in middle or old age. Almost half of cases require a high level of long-term care, resulting in significant social and economic burden. In 2006, 26.6 million individuals were affected by AD worldwide, with some estimates predicting a fourfold increase in global incidence to 1 person in 85 by the year 2050. The prevalence and severity of this disorder thus makes it a significant public health issue and an important target for drug discovery. Current treatment options are unfortunately limited, providing at best a modest and transient reduction of specific symptoms.

There is strong evidence that mitochondrial dysfunction is the primary causal factor in AD. However, the detailed exploration of mitochondrial impairment has been in part limited by the lack of a robust and non-invasive method for the quantitative characterization of oxidative function in the human brain. Positron emission tomography (PET ) enables imaging of oxidative metabolism, however, it is presently cumbersome, requiring three administrations of 15O labelled tracers. After each imagining scan multiple samples are collected to determine blood radioactivity levels. This is arduous for patients and entails risks due to both the ionizing radiation exposure, and the need for arterial catheterization. To overcome these challenges, Dr. Hoge and his multidisciplinary team developed a novel MRI technology allowing for the rapid and non-invasive imaging of oxidative metabolism in the human brain. Their approach, termed QUO 2 (QUantitative O2) MRI , enables imaging during the delivery and following consumption of oxygen with superior spatial resolution and sensitivity and, importantly, without radiation exposure to PET . It can thus be repeated serially on individual patients, making it well suited to large-scale clinical trials, including longitudinal studies.

Impact on the drug discovery process

  • Significant potential to identify new mechanisms of action for future AD drugs.
  • Improve patient selection for appropriate treatment selection in clinical trials.
  • Provide new therapeutic endpoints for assessment of drug efficacy in clinical trials.
  • Guide personalized therapeutic intervention in individual patients depending on their relative vascular and mitochondrial burdens.

Richard Hoge

Institut universitaire de gériatrie de Montréal

Co-Investigators

Pierre Bellec, Sylvie Belleville, Oury Monchi, Yan Deschaintre et Julien Doyon
Institut universitaire de gériatrie

Christian Bocti
Université de Sherbrooke

Serge Gauthier
Université McGill

Douglas Arnold
NeuroRx

Mentors

James A. Goodman
Director, Clinical Research,
Pfizer WRD

Michael Klimas
Executive Director, Translational Biomarkers,
Merck

Yvonne Will
Senior Director, Head of Science and Technology Strategy,
Pfizer WRD