Miniature human brains grown in a Saskatoon lab are upending the way researchers see neurology and immunology. Neuroscientist Dr. Tyler Wenzel is using brain organoids to challenge decades of rodent-based research, charting a new course for precision medicine. As a high school biology teacher, Wenzel's students learned how hearts pump blood and lungs move air. But apart from neurological electrical activity, neither Wenzel nor the textbooks had many clear answers about the brain. During his graduate studies, Wenzel realized the same experimental question tended to produce opposite results for mice and humans. The key difference, he found, lay in how each species' responded to toxins and injury, leaving him skeptical of neurological therapies tested on rodents. Now an assistant professor of psychiatry at the University of Saskatchewan, Wenzel focuses on youth degenerative brain disease and the limits of traditional research models. He grows human brain organoids — "mini brains" — from pluripotent stem cells derived from sources like blood or skin. Measuring two millimetres apiece, those organoids resemble tiny blobs of chewing gum. "We will turn [cells from a patient] into pluripotent stem cells, and we will make their mini brain, and because it has their genetic information, we get a brain that has their pathology," Wenzel said. "If you do that same mutation, often in a mouse, the pathology won't appear. So it allows us to actually get a pathology we can actually study," he said. When Wenzel was first hired at the University of Saskatchewan in 2024, the budget-conscious researcher built his lab on a shoestring, picking up secondhand centrifuges, balances, fridges and freezers from industrial start-ups. That move saved him time, and hundreds of thousands of dollars. "All the money that we started off with, it is literally going to just the research team and directly to the research," Wenzel said, crediting NSERC and SHRF for their support. "I am so grateful." Today, Wenzel studies childhood cerebral X-linked adrenoleukodystrophy (ALD), a rare degenerative brain disease that strikes children, and is fatal when left untreated. His organoids may provide proof of concept for new ways to target the brain and nervous system, without the need for radiation, chemotherapy, and lifelong immunosuppresant drugs currently required for hematopoietic stem cell transplants. "Chemotherapy and irradiation makes holes throughout your whole body. So we can do it in just your brain, just your spinal cord, and then we can inject the immune cells specifically into those locations," Wenzel said. "That eliminates many of the things that make chemotherapy uncomfortable, many of the things that make any sort of stem cell transplant uncomfortable." This spring, Canada's Stem Cell Network singled out Wenzel's work with a Rising Star Award, saying his work demonstrates "leadership, creativity and potential for major impact". If his method shows promise in treating ALD, Wenzel's approach could pave the way for more targeted, effective and far less invasive treatments for a range of degenerative brain diseases.
