A GlycoNet project has identified a series of molecules that may hold the key to preventing and treating heart failure, a disease for which there is currently no cure.
Cardiomyocytes are the muscle cells of the heart and are responsible for generating contractile force, keeping blood pumping throughout the body. When these cells die, heart failure occurs with often devastating results. But project investigators have discovered a molecule that protects cardiomyocytes from death.
“If we treat [cardiac cells] with these molecules, we can prevent the cardiac cells from dying in response to anti-cancer treatment. Which means we can preserve cardiac function and prevent heart failure,” says Dr. Mona Nemer (photo inset, University of Ottawa), an investigator on the project along with Dr. Yvan Guindon (Université de Montréal and IRCM).
While many things can lead to heart failure, including conditions such as hypertension, hardening of arteries, or complications from diabetes, this project focuses on heart failure caused by chemotherapy.
“Some very effective anti-cancer drugs cannot be used at their optimal dose or with many people because it’s known they would lead to heart failure,” says Nemer. “Initially we set out to develop a
way to protect the heart against heart failure that is induced by cancer treatment. We’re hoping that any developments will also be expanded to other types of heart failure.”
The team has already demonstrated the success of their lead molecule both in culture and in animal testing, and is hoping to continue to advance towards treatment of a disease that has unmet clinical need. Heart failure is the number one reason for hospitalization in people over 65.
“It’s a very serious condition,” says Nemer. “Right now, there are no therapies available to stop, slow down, or cure heart failure. As a result, it’s a diagnosis that can be worse than some cancers. Fifty per cent of the individuals diagnosed with heart failure will die within five years.”
Whether the drug could also reverse heart failure once it has progressed will determine the breadth of application of the drug, and it’s something the team is still investigating.
“The results are very encouraging, showing that it can prevent the onset of heart failure in conditions where the heart has already started to go down that path,” says Nemer. “Some of the experiments we’d like to do moving forward are to see the extent to which the drug can be effective – can it be given at mid-course heart failure, at end-stage? Are we able to stabilize once the disease has set in and at what stage?”
The group will also be doing more extensive pre-clinical studies, with the hopes of eventually moving to clinical studies. Nemer credits their success so far to fundamental studies in carbohydrate chemistry and in the effects of anti-cancer drugs, which were applied together thanks to the collaboration enabled by GlycoNet.
“A project like this cannot be carried out except with a multidisciplinary team because it’s an iterative process,” she says. “That’s the goal of a network like GlycoNet – to take basic discoveries and enable their translation into innovations that can be of socioeconomic benefit.”