![Associate Professor of Health Sciences Rebecca MacPherson and PhD student Emily Copeland sit at a counter in a lab while wearing white lab coats.](https://brocku.ca/brock-news/wp-content/uploads/2023/03/Rebecca-MacPherson-and-Emily-Copeland-1600x1067.jpg?x91846)
What began as a simple conversation between colleagues has evolved into transdisciplinary research revealing a link between two well-known diseases.
While Brock researchers Rebecca MacPherson and Val Fajardo were talking one day, the powerful idea emerged that muscle health and the brain are connected, leading to a promising research collaboration.
Brain structures and functions are MacPherson’s expertise. The Brock Associate Professor of Health Sciences studies how changes in protein regulation in the brain contribute to Alzheimer’s disease.
Meanwhile, muscle expert Fajardo, Assistant Professor of Kinesiology, examines how overactivation of a particular enzyme can lead to Duchenne muscular dystrophy (DMD), a disease characterized by progressive muscle wasting and weakness.
While it is known that patients with DMD can also exhibit declines in thinking and reasoning such as memory loss, lower IQ scores and confusion, how or why this occurs is unknown.
One of MacPherson’s students came across a research paper showing that people suffering with DMD also exhibit higher circulating amyloid-beta peptides, a hallmark characteristic of Alzheimer’s disease.
“The production of amyloid-beta is something that we focus on in our research related to brain health,” says MacPherson. “So, Val and I wondered if this is something that is changing in the brain with DMD. That’s how this collaboration all started.”
Fajardo, Canada Research Chair in Tissue Remodelling and Plasticity throughout the Lifespan, and MacPherson pulled together a team of students, including a visiting international student, to study brain markers in animals modelling DMD and found similarities in the Alzheimer’s disease process.
“Interestingly, the same protein that Val was targeting to improve muscle health in Duchenne muscular dystrophy is also found in the brain, and its activity is related to Alzheimer’s disease,” says MacPherson.
Fajardo and MacPherson co-supervise PhD student Emily Copeland, who was a member of the research team. Copeland has continued exploring the dynamics of the protein found in both diseases, a link MacPherson says hasn’t been widely investigated and could lead to deeper understanding of what happens with Alzheimer’s disease and DMD.
The protein is glycogen synthase kinase, or GSK3 for short. Previous research has linked the overstimulation of GSK3 to muscle and bone deterioration. Fajardo is leading two projects to study how a drug called tideglusib and the metal, lithium, can reduce GSK3 production, which would stop and even reverse muscle and bone deterioration.
Copeland is examining whether reducing the activation of GSK3 and another protein called BACE1 would halt, and even reverse, the brain deterioration seen in models of DMD.
In her early results from pre-clinical DMD models, Copeland found that reducing GKS3 and BACE1 content improved memory and reduced amyloid-beta in the brain.
“By teasing out the mechanisms and how everything works, we think tideglusib can be used in a whole different way, as a therapy for DMD and Alzheimer’s disease, which is very cool,” says Copeland, who will be one of three lead authors on an extensive journal paper describing the team’s results that span from muscle to brain.
The results of Copeland’s research are part of a larger partnership Fajardo has with the British biopharmaceutical company AMO Pharma Inc. to help develop the company’s tideglusib drug.
For Copeland, her brain research — inspired by her neuroscience undergraduate years at Brock — is also deeply personal.
“My grandpa had Alzheimer’s; it runs in my family,” says Copeland, adding that their local Alzheimer’s Society provided her grandfather with much support.
“My grandparents had lots of help from them,” she says. “I figured that, through my research, I would give back and by helping someone else’s grandparent.”