Catalyzing bipolar disorder research

Paola Arlotta, PhD, holds up a vial of clear fluid swirling with tiny orbs. When she shakes her wrist, the shapes flutter like the contents of a snow globe.

“Those small spheres swirling around are actually tiny pieces of human cerebral cortex, except instead of coming from the brain of a person, they were made in the lab,” says Arlotta, the Golub Family Professor of Stem Cell and Regenerative Biology in the Harvard Department of Stem Cell and Regenerative Biology, a joint department of the Harvard Faculty of Arts and Sciences (FAS) and Harvard Medical School.

Those minuscule shapes may represent a giant opportunity for breakthroughs in understanding and treating bipolar disorder, a mental health condition that affects about 8 million people in the U.S. These lab-grown “organoids”—brain-like tissue engineered from blood cells of living patients—offer a means to discover more effective drugs and develop more personalized treatments for those with bipolar disorder.

This research is just one example of the diverse projects funded by the Bipolar Disorder Seed Grant Program of the Harvard Brain Science Initiative (HBI), a collaboration between FAS and HMS. Over the last decade, the program has funded more than 90 projects across Harvard University and its affiliated hospitals and hosted five symposia. In some cases, the grants have enabled researchers to develop innovative approaches that later attracted larger grants from major funding agencies and resulted in publications in prominent journals such as Nature.

The program began in 2015 with the first of a series of gifts from the Dauten Family Foundation, which recently gave an additional $3 million to boost the program, bringing the foundation’s total support to $12 million. Kent Dauten, MBA ’79, and his wife, Liz, took up the cause after two of their four children were diagnosed with bipolar disorder despite no known family history of the illness. “We worked closely with the HBI team to create the program and attract more of the best and brightest up-and-coming neuroscientists and their lab teams into the field of bipolar disorder research,” says Kent Dauten.

Thanks to the Dautens’ support and a generous contribution from another donor, the program has expanded and this year funded 11 projects. These projects will receive $174,000 over two years and will investigate bipolar disorder causes and treatments from perspectives including genetics, brain circuitry, sleep, immune dysregulation, stress hormones, and gut bacteria.

Kent Dauten describes bipolar disorder research as an area that remains significantly underfunded but has become an exciting frontier for discoveries that could alleviate the suffering of millions of individuals and their families. “This has been and remains our family’s top philanthropic and volunteer priority,” he says, “and we are very happy with the success of the program and our partnership with HMS and HBI.”

As for Arlotta, who has spent more than a decade developing human brain organoids, she knows that no single research approach represents a panacea. Because bipolar disorder remains so mysterious, the seed grant program is valuable because it promotes many promising lines of research across disciplines.

“The program has the modesty of understanding that we know very little about bipolar disorder,” says Arlotta. “Therefore, we need to have multiple shots on goal.”