Decoding the brain’s biology to cure neurological diseases.
The human brain is among nature’s greatest astonishments and most enduring mysteries. We know that its power derives not only from the structure of individual cells, but the structure of their interconnections. For researchers, that creates a fundamental limitation: we can only learn so much from a static brain. Without blood flow, brain function falls precipitously. The necessity of studying brains post-mortem limits progress on understanding and treating complex and common central nervous system disorders, like Alzheimers and Parkinson’s disease. “Understanding the intricacies of the brain is one of the greatest scientific and clinical challenges of our time,” says Dr. Nenad Sestan, co-founder of Bexorg, executive director of the Yale Genome Editing Center, and professor of neuroscience, comparative medicine, genetics, and psychiatry at Yale School of Medicine.
Spun out of the Kavli Institute for Neuroscience at Yale, Bexorg is revolutionizing brain science with a technology platform capable of studying intact and metabolically active mammalian brains. Based on academic research that yielded several high-profile and landmark publications in Nature, Bexorg uses a perfusion system to “reboot” brain cells, allowing for scalable, reproducible, and continuous molecular tracking of whole brain cultures. Unlike existing tools, these are physiologically active brains with preserved circulation, allowing for the creation of datasets of unprecedented fidelity, dynamism, and size—ideal for analysis using ML and AI tools. ”Our system gives us a level of control over these isolated brains so that we really get to understand what is happening inside that black box,” explains Dr. Zvonimir Vrselja, co-founder and CEO of Bexorg. “Now, we are directing that ability towards drug discovery and development.”
Bexorg’s perfusion technology arose out of an impasse in Sestan’s neuroscience research. He saw that a fuller understanding of the human brain’s astonishing capacity required dynamic analysis of large—ideally human—brains. But the information he wanted could only be gleaned from metabolically active brains. Collaborating with Vrselja, they developed a method that combined artificial blood, a device not unlike a heart-lung machine, and specialized control software, to restore brain cell function, even hours after death. (They subsequently adapted this perfusion system to preserve bodily function beyond the brain, extending the viability of organs for donation.)
As a discovery company, Bexorg is focused on the brain. “The isolated brain is our sandbox,” says Vrselja. The perfusion technology is now the foundation of a platform to assemble the world’s most comprehensive and accurate understanding of the brain. Within its controlled environment, Bexorg can precisely measure all inputs, outputs, and conditions. Researchers are able to image intact and metabolically active brains, as well as study the pharmacokinetics, blood brain barrier penetration, mechanisms of action, and pharmacodynamic responses of any potential therapeutic modality. Bexorg’s expanding data collection system is highly dimensional, allowing for longitudinal sampling, and ideal for the creation of petabyte-scale datasets, for use in ML- and AI-driven drug discovery. The overall aim is the development of a proprietary end-to-end pipeline that uses a continuously improving in silico model of the brain to accelerate the development of novel therapies. Bexorg’s initial focus is Parkinson’s disease, with plans to broaden out to other central nervous system disorders.
“Our vision is a world without brain diseases,” says Vrselja. “We finally have a platform that allows us to understand, probe, and find solutions that repair the biology and function of the brain. With Bexorg’s platform, we will create solutions to achieve this vision. The medical need is there.”