New study shows 'mini-brains' could speed development of Alzheimer's disease treatment

Using an innovative new method, a University of Saskatchewan (USask) researcher is creating miniature pseudo-organs from stem cells to diagnose and treat Alzheimer's disease.

When Dr. Tyler Wenzel, Ph.D., first came up with the idea of creating a miniature brain from stem cells, he had no idea how successful his creations would be. Now, Wenzel's "mini brain" could revolutionize the way we diagnose and treat Alzheimer's and other brain diseases.

"Never in our wildest dreams did we think our crazy idea would work," he said. "These [mini-brains] could be used as a diagnostic tool made from blood."

Wenzel, a postdoctoral fellow in the College of Medicine's Department of Psychiatry, developed the idea of the "mini-brain" — or, more formally, a unique model of a cerebral organoid — under the guidance of Dr. Darrell Musso, Ph.D.

Human stem cells can be manipulated to become almost any other cell in the body. Using stem cells taken from human blood, Wenzel was able to create a miniature artificial organ—about three millimeters in size, visually resembling a piece of chewing gum that someone has tried to smooth out again.

These "mini-brains" are created by creating stem cells from a blood sample, then converting those stem cells into functioning brain cells. Using small synthetic organoids for research is not a new concept, but the "mini-brains" developed in Wenzel's lab are unique. As described in Wenzel's paper in the journal Frontiers of Cellular Neuroscience, the brains in his lab are made up of four different types of brain cells, while most brain organoids are made up of only neurons.

In testing, Wenzel's "mini-brains" more accurately reflect adult human brains, allowing for more detailed studies of adult neurological conditions such as Alzheimer's disease.

And for those "mini-brains" created from stem cells from people with Alzheimer's, Wenzel found that the artificial organ exhibited Alzheimer's pathology—only on a smaller scale.

"If stem cells can become any cell in the human body, the question became, 'Can we create something that resembles an entire organ?'" Wenzel said. "As we were developing this, I had this crazy idea that if these were actually human brains, if a patient had a disease like Alzheimer's, and we grew a 'mini brain,' then, theoretically, that little brain would have Alzheimer's."

Wenzel noted that this technology has the potential to change the way health care is delivered to people with Alzheimer's disease, especially in rural and remote communities. This pioneering research has already received support from the Alzheimer Society of Canada.

If Wenzel and his colleagues can create a reliable way to diagnose and treat neurological diseases like Alzheimer's using just a small blood sample — which has a relatively long shelf life and can be shipped by courier — rather than requiring patients to travel to hospitals or specialty clinics, it could significantly save health care resources and reduce the burden on patients.

"Theoretically, if this tool works the way we think it does, we could just get a blood sample sent from La Loche or La Ronge to the university and diagnose you that way," he said.

The initial proof of concept for the "mini-brains" has been extremely encouraging - meaning the next step for Wenzel is to expand testing to a larger patient pool.

The researchers are also interested in expanding the scope of their mini-brain research. If they can confirm that the mini-brains accurately reflect other brain diseases or neurological conditions, they could be used to speed up diagnosis or test the effectiveness of drugs in patients, Wenzel said.

As an example, Wenzel pointed to the long wait times to see a psychiatrist in Saskatchewan. If the "mini-brains" could be used to test which antidepressant drug works best for a depressed patient, it could significantly reduce the time it takes to see a doctor and get a prescription.

A 'mini-brain' in a petri dish - when created from stem cells from people with Alzheimer's, the organoids exhibit Alzheimer's pathology, only on a smaller scale. Credit: USask/David Stobbe.

A former high school science teacher who moved into the world of research and academia, Wenzel said it's "the essence of research" — coming up with a hypothesis and getting closer to testing it in an experiment — that excites him about his work.

The stunning success of the initial "mini-brains" was so astonishing that Wenzel admitted that he still cannot fully comprehend it.

"I'm still in disbelief, but it's also incredibly motivating that something like this has happened," Wenzel said. "It gives me something that I think will impact society and make a real difference and create change... it has the potential to change the landscape of medicine."

The results of the work are described in detail in an article published in the journal Frontiers in Cellular Neuroscience.