Not alive, but not dead: disembodied human brains used for drug testing

By restoring some functions to intact brains from deceased donors, the startup Bexorg hopes to create a better drug development test bed for neurodegenerative diseases

20 May 202611:40 AM ETBySara Reardon

A scientist checks a human brain maintained on life support

Photographed through a window, Bexorg scientist Luis Gonzalez checks a human brain maintained on life support.S. Reardon/Science

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NEW HAVEN, CONNECTICUT—Just a day ago, the brain was in a living person. Now, hours after its owner died, it sits on a cart draped in tubes that quiver as they pump liters of blood substitute and other fluids through the organ, supplying oxygen and removing waste. With most of its key functions intact but its electrical activity quenched by anesthesia, the brain hovers between life and death. As it metabolizes experimental drugs, sensors record its reactions, capturing hundreds of data points on its cells, proteins, and physiology. Then, after 24 hours in this state, it will be sliced into hundreds of pieces for more detailed study.

The brain is one of more than 700 that the 5-year-old biotech startup Bexorg has nurtured and studied using a set of proprietary brain-sustaining machines it calls BrainEx. The platform grants researchers an intimate look into how potential therapies might work inside brains with neurodegenerative diseases such as Parkinson’s, Alzheimer’s, or amyotrophic lateral sclerosis. Bexorg can biopsy the brains and discover how long a drug stays in cells, whether it hits its molecular target, and any hints of side effects.

The system promises far more realistic conditions for testing drugs than lab animals or cells in a dish, its developers say. Whole brains come with decades of environmental exposures, histories of drug treatments, and unique genetics that can affect responses to experimental medicines, says physician Zvonimir Vrselja, one of Bexorg’s founders and CEO. “You get cells that have been there for 60 to 80 years.”

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Early results, including a 2025 poster reporting that the preserved brains match living brains in their response to certain therapies, are encouraging, says Bruna Bellaver, who studies neurodegeneration at the University of Pittsburgh. “It’s a huge step up from mouse models,” she says of the platform.

Bexorg has largely stayed under the radar. Its founders have published no papers on its work other than early experiments with pig brains, although Vrselja says they are preparing their first paper on human ones. Now, the company is scaling up and inviting new attention. Its new lab space, which Science visited last week, will house a 1.2-meter-tall robotic arm to automate the process of slicing up to 1600 brains per year and analyzing 11,000 proteins in each. At a media event today, the company will showcase Bexorg’s assembly line process—and seek to reassure the public that its disembodied brains don’t cross ethical lines or risk regaining consciousness.

Insights from these brains will soon be put to the test: At least one of Bexorg’s collaborators, the pharmaceutical company Biohaven, is launching a clinical trial of a drug meant to boost energy supplies in ailing brains based, in part, on data gathered in Bexorg brains. Biohaven’s chief science officer, Bruce Car, thinks that by predicting a therapy’s safety and efficacy better than animals or cell models can, the system could shave years and millions of dollars off traditional drug development processes. So far, he says, “The technology has been everything it’s been promised to be.”

The BrainEx machines sit in six plexiglass cubicles in an office overlooking Yale University, where Vrselja, neuroscientist Nenad Sestan, and their colleagues conceived of the idea 10 years ago. Before each brain is placed in a machine, surgeons examine it through a loupe, then suture four plastic ports into the vessels that once supplied it with blood so it can start reacting to drugs and generating data. Once the brain is attached to the BrainEx machines, an artificial lung and kidney oxygenate and filter fluids as they flow through the organ.

Vrselja and Sestan first used the approach to restore function to the brains of pigs obtained from a local slaughterhouse. They reported the results in a 2019 Nature paper—and promptly faced concerns that the brains might preserve traces of consciousness, feel pain, or retain memories.

The brains are already almost devoid of the coordinated neural firing necessary even for minimal consciousness, says Brendan Parent, a bioethicist at New York University Langone Health and one of six ethicists on Bexorg’s advisory board. But the company also forestalls any electrical activity with the anesthetic propofol, among other measures. Bexorg obtains brains in partnership with organizations that procure donated organs for transplantation, and Vrselja says once families understand the company’s process and goals, their response is overwhelmingly positive.

Animal models have clear shortcomings, especially when it comes to testing drugs in the brain. There’s no guarantee that a drug that passes easily into a mouse’s brain will do the same in a human’s, and a harmful overdose or ineffective underdose can stop a promising therapy in its tracks. “This is threading a needle at the best of times,” Car says. “Sometimes you get it right from your [animal model] and sometimes you miss entirely.”

Recent efforts by the U.S. government to push researchers and drugmakers away from animal testing in favor of human-based systems or computer models also represent “a huge tailwind for us,” Vrselja says.

The company has raised $42.5 million to date, not including several grants and partnerships with biotech companies and universities whose amounts Bexorg declined to disclose. Beyond testing drugs—including some developed by Bexorg itself—the brains might reveal new markers of disease processes, such as neurodegeneration in Alzheimer’s, that could be useful to physicians for diagnosis and monitoring.

The approach is especially well-suited for studying neurodegenerative disorders because these don’t generally involve brain electrical activity, Vrselja says, and because donors’ brains often have more than one such condition—a phenomenon that’s been difficult to re-create and study in the lab.

Car’s team at Biohaven has used about 130 of Bexorg’s brains to test several drugs, including one intended to prevent toxic proteins from building up in the brain in diseases like Parkinson’s. The drug didn’t interact with its target in a mouse, but Car says it worked in human brains at a dose 20 times lower than the company had initially calculated—saving the company a year of development and potentially preventing the risk of serious side effects.

Biohaven is also developing a compound called BHV-8100, which interacts with metabolic enzymes to increase the brain’s energy and allows neurons to use glucose more efficiently. These metabolic pathways are damaged in many neurodegenerative conditions. The U.S. Food and Drug Administration has approved Biohaven’s application to begin clinical trials with BHV-8100 supported by data from the Bexorg brains; later this month the company will announce which disease it is targeting.

Already, “It’s a remarkable brain bank,” says Li-Huei Tsai, a neuroscientist at the Massachusetts Institute of Technology who uses brain organoids grown from human stem cells and chips that mimic the blood-brain barrier to study neurodegeneration. She points out that BrainEx brains may not be perfect models for living ones—the systems that drain fluid from the brain might work differently in a full human body, for instance, and preventing neurons from firing can affect how blood flows through the organ. Car adds that because the brains lack electrical activity, they may not indicate whether a drug will cause seizures, although the company plans to eventually remove the anesthesia from some brain slices. Car says other models can fill in the gaps.

As Bexorg expands, it may take on other disease areas, including psychiatric disorders and cancer, Vrselja says. Eventually, the team hopes to maintain brains in BrainEx for up to 2 weeks in an effort to gather far more data about long-term processes such as brain plasticity in response to treatments.

The company is also developing a machine learning model called NeuroLens that acts as a “virtual brain,” trained on the brain readouts, donors’ medical records, and protein and microscopy data from brain tissue. The model could eventually allow researchers to test new drug molecules before even going into a physical brain. In this virtual form, the pampered brains in Bexorg’s lab will live on even after their life support is withdrawn.

(http://www.autoadmit.com/thread.php?thread_id=5867801&forum_id=2#49892391)