Personalized medicine for Bipolar disorder: clinical lithium response as a guide to mode of action and biomarker discovery using human neurons and biofluids

Project Overview

Bipolar Disorder (BD) is a chronic psychiatric illness, ranking in the top 10 causes of disability and mortality worldwide, due to suicide and cardiovascular death. BD affects ~3% of the global population and >500,000Canadians. Typically, the disease starts during adolescence and has a life-long course, characterized by extreme states of mania and depression, often associated with psychosis and self-harm. The cause of BD is unclear, with a combination of genetic and environmental factors likely to contribute. Given the complex heritability and symptoms of BD, long term clinical management of many patients remains unsatisfactory. Thus, there is a major unmet need for new clinical treatment strategies and drug options to help these patients. To provide better treatments for this disorder, we propose a personalized medicine approach that will yield a better understanding of its biological basis; a realization that would define biological signatures that could help predict responsiveness to therapy. The best treatment for BD is lithium, which due to its effectiveness as a mood stabilizer allows many patients to regain social and occupational functioning. However, lithium is effective in only 30% of BD patients, and the reason why remains elusive. To address this, we will use induced pluripotent stem cell (iPSC) technology to grow human neurons from patient blood samples. This will allow us to study how lithium acts on brain cells, and examine neuronal structure and function of BD patient neurons, with respect to those from non-BD sufferers. Ultimately, this project aims to improve our understanding of BD disease processes, and learn more about how lithium works in some people and not others. The results may provide a signature with which to predict the efficacy of treatment. This would speed-up treatment choice, accelerate recovery, and reduce years of suffering in many patients, in addition to cutting costs.

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