A genomic-imaging analysis of the GENetic Frontotemporal dementia Initiative (GENFI): Development for a robust clinical trials platform

2014  -  Toronto, ON, CA

Organizations

Sunnybrook Health Sciences Centre, University of Toronto, Centre for Addiction and Mental Health, Laval University, London Health Sciences Centre

Project description

There have been three major genes discovered that cause familial forms of frontotemporal dementia (FTD), a devastating group of disorders associated with personality and behavioural changes and/or language difficulties in those suffering. The impact to individuals and their families is huge because FTD affects those in the prime of their lives, often between the ages of 45 to 55. The gene abnormalities predict that an individual who harbours one of them will be at high risk of developing symptoms, but does not predict when this will occur and what features they will have. Therefore, it is critical that studies concentrate on developing powerful markers using brain imaging and genetics that can identify the earliest stages of disease before symptoms develop. It is hoped that novel drugs being developed can be used to eventually prevent the disease from starting in those at risk.

 Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging

This project will combine genomics and neuroimaging methodologies to develop tools that can be used to identify and track the earliest brain changes seen in those at genetic risk of developing FTD. These tools will also be used to identify genomic factors that lead to clinical heterogeneity in genetic FTD. A major goal of the Genetic Frontotemporal Dementia Initiative (GENFI) is to build a robust trials platform, with both a cohort of potential participants and an assessment protocol that is designed and powered for clinical trials in premanifest and early disease, with appropriate clinical and biomarker endpoints.

Anticipated outcome

It is anticipated that through using the combination of genetics and neuroimaging technologies, we will be able to identify those at highest risk for developing FTD, what age will they be at the time of onset of symptoms, and more specifically whether they will present with either behavioural or language features. In addition, the information gained from this project will help to determine when the correct time will be to initiate potential disease modifying therapies that are in the drug development pipeline, and also whether imaging or fluid markers can be used as outcome measures.