The researchers used an antibody to selectively activate a receptor in a molecular signaling pathway to develop dopaminergic neurons. These neurons produce dopamine, a neurotransmitter critical to brain health.

Researchers around the world have been working to coax stem cells to differentiate into dopaminergic neurons, to replace those lost in patients living with Parkinson’s disease. But efforts have been hindered in part by an inability to target specific receptors and areas of the brain.

“We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway,” said Stephane Angers, principal investigator on the study and director of the Donnelly Centre for Cellular and Molecular Biology.

“We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway,” said Angers, who is also a professor in the Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicine, and holds the Charles H. Best Chair of Medical Research at U of T. “This activation method has not been explored before.”

The study was recently published in the journal Development.

Parkinson’s disease is the second-most common neurological disorder after Alzheimer’s, affecting over 100,000 Canadians. It particularly impacts older men, progressively impairing movement and causing pain as well as sleep and mental health issues.

Most previous research efforts to activate the Wnt signaling pathway have relied on a GSK3 enzyme inhibitor. This method involves multiple signaling pathways for stem cell proliferation and differentiation, which can lead to unintended effects on the newly produced neurons and activation of off-target cells.

“We developed an efficient method for stimulating stem cell differentiation to produce neural cells in the midbrain,” said Andy Yang, first author on the study and a PhD student at the Donnelly Centre. “Moreover, cells activated via the FZD5 receptor closely resemble dopaminergic neurons of natural origin.”

Another promising finding of the study was that implanting the artificially-produced neurons in a rodent model with Parkinson’s disease led to improvement of the rodent’s locomotive impairment.

“Our next step would be to continue using rodent or other suitable models to compare the outcomes of activating the FZD5 receptor and inhibiting GSK3,” said Yang. “These experiments will confirm which method is more effective in improving symptoms of Parkinson’s disease ahead of clinical trials.”

This research was supported by the University of Toronto Medicine by Design program, which receives funding from the Canada First Research Excellence Fund, and the Canadian Institutes of Health Research.

Photo taken in October 2023 of the Maxus rocket monument, a symbol of space exploration in Kiruna, Sweden. (Kyodo)

Photo taken in October 2023 of Manabu Shimoyama of the Swedish Institute of Space Physics, and a model of Viking, the country’s first artificial satellite, in Kiruna, Sweden. (Kyodo)

One of the researchers is Manabu Shimoyama, 49, who came to the IRF in 2015 after studying in Japan and Canada. He is involved in the European Space Agency’s Jupiter Icy Moons Explorer, or JUICE, project, which operates an interplanetary spacecraft designed to study Jupiter and its three icy moons: Ganymede, Callisto and Europa.

He serves as a coordinator between Japan and Sweden, which jointly developed some of the equipment on board the JUICE probe that was launched in April 2023 and is expected to enter orbit around Ganymede for observations in 2034.

Sweden is a member of the ESA, and the IRF is much smaller in scale than the National Aeronautics and Space Administration of the United States, as well as the space exploration agencies of other big countries.

Shimoyama says there are many positive sides and benefits of working at the IRF. “Since researchers and engineers are at the same facility, ideas take shape faster,” he said.

Cooperation in space exploration between Japan and Sweden took off in 1998 with the Japanese Mars orbiter, called Nozomi, and has continued with lunar, Mercury and Venus exploration projects.

“I think (Japan and Sweden) have been jointly involved in almost all missions in one way or another. Their strong ties are definitely noteworthy,” Shimoyama said.

With a population of about 23,000, Kiruna is famous for tourism built around the dazzling northern lights and the original Icehotel, made each year out of snow and ice. It also features the Maxus rocket monument as a symbol of the space exploration research city. Some Japanese experts have been studying there for two or three decades.

Photo taken in October 2023 of Yoshifumi Futaana explaining his research in Kiruna, Sweden. (Kyodo)

Yoshifumi Futaana, 48, who specializes in heliophysics (the study of the Sun and its connection with the solar system) came to Kiruna in 2003 to get involved in Mars exploration. Futaana praised the IRF for its “spirit of pursuing original and ambitious studies.”

Recently, young Japanese researchers have been coming to the IRF through connections with Futaana and others. Given the long-term nature of space exploration research, it is important to pass on the baton to the next generation.

“We want to do more joint work with Japan. To this end, it is essential to develop talent in Japan,” Futaana said.