Dr. Jean-Martin Beaulieu: Developing Potentially Safer Bipolar Disorder Treatments

Rising Star Awardee Jean-Martin Beaulieu, Ph.D., is investigating the roots of bipolar disorder treatment, with surprising and useful results. 

Lithium has been one of the most-prescribed treatments for bipolar mania since its FDA approval in 1970. Many with bipolar disorder rely on lithium to stabilize their mood long-term, but the treatment may produce serious side effects, particularly if blood levels become imbalanced or with prolonged use. If safer mood stabilizers could be developed, many afflicted people would benefit.

Jean-Martin Beaulieu, Ph.D., Associate Professor of Psychiatry and Neurosciences at University of Toronto, and winner of the 2014 One Mind Institute / Johnson & Johnson Rising Star Translational Research Award, is building on his previous discoveries to generate and test the efficacy of specific, novel small molecules to remedy manic-like behavior in mice. Because these molecules are precisely targeted to act on one of lithium’s main therapeutic mechanisms, they replicate the therapeutic effect of lithium while potentially minimizing side effects. And, his team's investigations are revealing a deep understanding of how all mood stabilizers work, opening new paths for even safer medications for bipolar disorder.

Building a Better Lithium

Beaulieu’s previous research has revealed the chemical process behind one of lithium’s known means of therapeutic action, the inhibition in the brain of a protein, GSK-3, which is involved in inflammation and cell death. By experimentally determining that this inhibition depends on lithium’s disruption of the interface between two enabling proteins, Akt and beta-arrestin2 (βArr2), Beaulieu and his team uncovered a new frontier for mood stabilizer development: targeting of the Akt/βArr2 interface. Their original hypothesis: Small molecules which selectively block the interface between the proteins Akt and βArr2 may be able to replicate the therapeutic effect of lithium in a much more benign way.

In 2015, Beaulieu’s team began to confirm this hypothesis. Testing the effect of a specific Akt/βArr2-disrupting protein, his team observed that it replicated the effects of lithium on Akt in the mouse brain. And, they found behavioral changes in these mice that mirrored some of the therapeutic effects of lithium.

Furthermore, they confirmed that the Akt/βArr2 interface is basic to the therapeutic action of two other mood stabilizers, lamotrigine and valproate. And, they traced this mechanism of action to find that it influences the schizophrenia risk gene FXR1P, suggesting that these drugs might affect brain development relevant to a variety of psychiatric conditions.

Assisting the Brain’s Natural Balance?

Investigating further in 2016, Beaulieu’s team has now discovered evidence suggesting an even deeper explanation for these mood-stabilizing drugs’ efficacy: they appear to regulate homeostatic plasticity, a natural process of neurodevelopment that helps the brain’s circuit activities stay in balance.

By strengthening homeostatic plasticity, could future medications that target the Akt/βArr2 interface help keep the brain stable under clinically severely stressful circumstances? In 2017, Beaulieu and his team will test lithium and the novel molecules they have developed to characterize their influence on homeostatic plasticity.

A Star that Keeps Rising

The potential of the Beaulieu team’s Rising Star Award-funded science has earned them a major grant in 2016 from CQDM and Brain Canada, to develop a drug assessment process to help pharmaceutical and biotech companies rapidly discover new medications, to ultimately help those living with bipolar disorder.

We at One Mind Institute congratulate Dr. Beaulieu on his exciting discoveries, and are grateful to our donors for enabling us to fund this leading scientist.

Watch Dr. Beaulieu's talk at One Mind Institute's 2014 Music Festival for Brain Health:

"As a family member of someone living with schizoaffective disorder, I am proud to support One Mind Institute’s profoundly important work. One Mind Institute allows those touched in some way by psychiatric illness to take action and work toward solutions by helping to spur early stage research. One Mind Institute’s audacious mission to find a cure for psychiatric illness in one generation is what it will take to make meaningful progress, and holds the promise of changing millions of lives around the globe. "
"From the moment I found One Mind Institute and met the amazing Staglin family I knew that my advocacy would grow by leaps and bounds. Through their dedication and commitment I found a community of brilliant scientists, passionate philanthropists, music lovers and a new mental health family to call my own. I cherish the work One Mind Institute does every day to advance the research on brain disorders, to increase the awareness around mental illness and mental health and to create a community of love and support for advocates everywhere. I would not be the person I am today without the inspiration One Mind Institute has provided me."
"One Mind Institute has distinguished itself as a leader in the fight against brain disease. One Mind Institute’s vision of a world without mental illness seems beyond reach only to those who have not seen firsthand the intensity of One Mind Institute’s dedication and focus. These folks are not giving up until they’ve won. The Saks Institute is delighted to be One Mind Institute’s partner in the fight."
"When I heard of the groundbreaking work the Staglins were doing through their organization One Mind Institute, such as research into preventing schizophrenia from ever occurring, I hoped to meet them. When I did I was amazed by their non-stop energy and complete devotion to the cause. But most of all, I was moved by their sincere desire to share ideas with people from all backgrounds and fields. As I continue to create films to inspire empathy for those with mental illness, I remain inspired by the Staglins and what One Mind Institute has done to transform mental health research and improve lives. "
"The support of One Mind Institute has been absolutely essential to all of the psychosis prediction and prevention efforts of CAPPS and the NAPLS. On behalf of the patients and families who have received high quality clinical services in our program regardless of their ability to pay, and on behalf of the numerous dedicated members of our research and clinical treatment teams, I am so incredibly grateful for One Mind Institute’s generous contributions. On a personal note, it is very inspiring to see the huge gains made for mental health research and awareness over the past several years, which have been sparked in large part by the efforts of the Staglin family."
"One Mind Institute, thank you again for funding CAPPS/ABBRC. Our daughter, Anna, participated in the program 2012-2013 and just received her final assessment. While this research helps others, know how much we appreciated participating with such genuinely dedicated people (very well selected to work with adolescents). It was very helpful for us as well, and provides us with even more hope. We're so impressed with the program."
"Having struggled with schizophrenia since a young woman, I am deeply grateful for what One Mind Institute does. One Mind Institute’s unwavering commitment to support research is an inspiration to those of us who long for the day when a cure for serious mental illness is found. I think of One Mind Institute as a good friend and kindly mentor who has taken up my cause and fights for my mental health each and every day."
"One Mind Institute is an organization equal parts compassion and science. A critical component of their work is advocacy and voice for millions of people who live with mental illnesses. Equally important is the incredible efforts they provide to further research in learning more about the brain and identifying effective treatments for brain diseases. One Mind Institute is a leader in the field of mental illness!"

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