Prof. Terry Hébert is noticeably upbeat these days, and for good reason.
Thanks to a generous $1.6-million boost from the Fondation Courtois, the Department of Pharmacology and Therapeutics is now home to a state-of-the-art microscope that will play a pivotal role in research on dilated cardiomyopathy (DCM).
DCM is a condition in which the heart's chambers stretch and become thin, leading to a decreased ability to pump blood. The most common causes of DCM can be genetic or through exposures to chemotherapeutic drugs used to treat cancer. Complications can include heart failure, arrhythmias, blood clots and an increased risk of complications during pregnancy. Recent figures show heart failure affects over 600,000 Canadians, and close to 50% of patients with DCM die within five years.
![A professor and a graduate student with new piece of high-tech equipment](https://www.mcgill.ca/medhealthsci-alumni/files/medhealthsci-alumni/240205-100922-7284-terry_hebert_lab-400x600.jpg)
In partnership with heart failure specialist Dr. Nadia Giannetti (MDCM’91) at the Research Institute of the McGill University Health Centre (RI-MUHC), Hébert leads the Heart-in-a-Dish project, which is aimed at personalizing and improving the understanding and prevention of heart conditions, particularly DCM. It involves growing patient heart tissue in Petri dishes to create a disease-in-a-dish model.
![Three researchers in lab coats.](https://www.mcgill.ca/medhealthsci-alumni/files/medhealthsci-alumni/240205-102024-6825-terry_hebert_lab-3500_wide_0.jpg)
The project complements the Courtois Cardiovascular Signature Study, a 10-year research project co-led by Giannetti at the MUHC's Glen campus, which is collecting biological materials, MRI imaging and clinical data from participants, and seeks to understand all the factors that contribute to heart disease using artificial intelligence to puzzle out previously undetected patterns.
“This is big news,” says Hébert. “For example, when we take blood from a person with a cardiomyopathy and make muscle cells from the stem cells, they have the features of the patient’s disease. The experiments that we do require a type of microscope that can capture information from hundreds of thousands of cells simultaneously and can integrate that into a very rapid analysis of what’s going on in that patient. That’s part of the game changer, being able to model disease in individual patients.”
The new microscope captures images and analyzes them in ways that provide researchers with previously unattainable information. “Instead of getting an overall global response, it allows us to observe what we're measuring and actually track the response down to each cell in the dish, and we can look at the effects of therapies on individual cells,” Hébert explains.
Up until now the management of heart disease has been a one-size-fits-all approach where every patient receives medication in the same order and at the same doses. But as Hébert points out, men and women may be different in how they experience the disease. “We do see differences between male and female patients. We see clear differences between patients and control subjects, and I think that is going to feedback on their care at some point. We can now say to a patient, look at your cells and how they differ from our control subjects. We can see clear differences in how the cells respond to normal physiological stimuli and how they respond to therapeutic interaction.”
Therapy testing will allow researchers to experiment with medication in different orders, doses and combinations. “Using our cellular models as a surrogate for the patient, we can test these things in cells from the patient without having to subject them to a trial-and-error process, and then potentially suggest treatment to the cardiologist,” Hébert notes.
![Student at computer](https://www.mcgill.ca/medhealthsci-alumni/files/medhealthsci-alumni/240205-100545-7277-terry_hebert_lab-3500_wide_0.jpg)
Heart-in-a-Dish has partnerships with pharmaceutical companies that have recognized the value of these new testing methods and see the advantage of working with researchers to develop uses for their biosensors, says Hébert. “We have started a collaboration with two companies where we're actually testing their biosensors for different disease indications using this microscope. It's really scaled into a centrepiece of a lot of our ability to interact with many different stakeholders, right from patients up to big pharma. It's given us some ground to occupy and people see us. So, pharma understands the value of these models. Most companies are now moving into technologies such as stem cells and derived tissues. Drug companies realize they need people who do disease modelling in human samples and human tissues, so they're turning to programs like ours to connect.”
In the early days of drug development, scientists had to translate their findings from animal studies to human biology, but many failed: while they worked well in animals, they failed in humans. “We think that there's some use for the technologies and for the approaches that are tied to this microscope that will allow us to do a lot of earlier drug discovery work in human-relevant models,” Hébert says.
With files from Mark Witten for FMHS Focus.