New study demonstrates 'mini-brains' that could speed development of treatments for Alzheimer's disease

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] can be used as a diagnostic tool created from blood."

Wenzel, a postdoctoral fellow in the College of Medicine's Department of Psychiatry, developed the idea of a "mini-brain"—or, more formally, a unique cerebral organoid model—under the direction 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 reminiscent of a piece of chewing gum that someone tried to smooth out again.

These "mini-brains" are created by creating stem cells from a blood sample and 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 outlined in Wenzel's paper in the journal Frontiers of Cellular Neuroscience, the brains from his laboratory are composed of four different types of brain cells, while most brain organelles are composed only of neurons.

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

And for those “mini-brains” created from stem cells from people with Alzheimer's disease, Wenzel determined that the artificial organ exhibits Alzheimer's pathology—just on a smaller scale.

"If stem cells can become any cell in the human body, then the question becomes: 'Can we create something that resembles an entire organ?'" Wenzel said. "While we were developing this, I had this crazy idea that if these were really human brains, if a patient had a disease like Alzheimer's and we grew them 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 provided to people with Alzheimer's disease, especially in rural and remote communities. This groundbreaking 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 such as Alzheimer's using only a small blood sample - which has a relatively long shelf life and can be sent by courier - rather than requiring patients to travel to hospitals or specialized clinics, this can significantly save healthcare 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 the testing to a larger patient pool.

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

As an example, Wenzel pointed to the long wait times to see a psychiatrist in Saskatchewan. If "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 visit a doctor and get a prescription.

"Mini-brains" 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 "essentials 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 he still can't quite wrap his head around it.

"I'm still in disbelief, but it's also incredibly motivating that something like this happened," Wenzel said. "This 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 findings are detailed in a paper published in the Frontiers in Cellular Neuroscience journal.