A world leader in Alzheimer's disease is focused on slashing the impact of COVID-19

Targeting solutions

The escalation of COVID-19 has prompted a race around the globe for successful treatments for the virus – sometimes through unexpected avenues.

Most might assume there would be no connection between Alzheimer’s disease solutions and COVID-19. While COVID-19 involves rapid viral infection of the lungs, Alzheimer’s – the most common kind of dementia – is marked by the decline of memory, cognition and executive function. However, Dr. Donald Weaver, Director of the Krembil Research Institute, recognizes an overlap: the destruction of an organ’s function in both diseases that results in the collapse of immune response.

“Not only can this destruction derive from similar cellular and signaling pathways,” explains Dr. Weaver, “but a heightened risk to the elderly means that both diseases also share a common patient pool.”

Furthermore, societal COVID regulations have heightened the problems of those afflicted with Alzheimer’s and other forms of dementia by restricting their ability to engage and socialize. This confluence of factors is making life worse for these individuals, which could cause the disease to progress.

“In terms of people who are experiencing dementia, keeping mentally and physically active is extremely important to their well-being,” explains Dr. Weaver. “What we’ve experienced in lockdown is the opposite to both of those. People are isolated socially, and they are not going out as much they used to, which is also adding to depression.”

Dr. Weaver and his team are consequently exploring the pathological overlap between Alzheimer’s and COVID-19 in the hopes of finding a treatment for the virus. Specifically, their understanding of cellular and signaling pathways similar to Alzheimer’s disease – and the need for researchers across all specialties to target answers to the worldwide pandemic – has turned their attention to identifying effective drug solutions.

A PROMISING DRUG

When the body responds to a coronavirus infection, its immune system triggers an inflammatory response against the virus that is sometimes so sudden and strong that it becomes fatal. Addressing this issue in a pre-clinical study, Dr. Weaver and his team have shown that furosemide, a small molecule drug, has the potential to treat COVID-19 by reducing the harmful inflammation caused by the infection.

Furosemide is a diuretic commonly prescribed to treat high blood pressure, fluid build-up in the lungs and chronic kidney disease. The drug can be administered orally, intravenously and by inhalation. It is also safe, readily available and part of the World Health Organization’s (WHO) Essential Medicines List.

“While it usually takes many years to bring a new drug to market, we obviously don’t have that time – which is why we decided to repurpose existing drugs to accelerate the development of treatments for COVID-19,” says Dr. Weaver.

Searching through a library of 1,136 small molecules produced by the body, they found one molecule with significant anti-inflammatory potential known as 3-hydroxyanthranilic acid (3-HAA). They then looked for approved drugs that are similar in structure to 3-HAA.

Of the few candidates shortlisted, furosemide is the most promising. Cell culture studies revealed that furosemide preventing the production of pro-inflammatory molecules, and promoted the production anti-inflammatory molecules.

“Our pre-clinical study suggests that furosemide may be a candidate for repurposing as an inhaled therapy against COVID-19,” says Dr. Weaver. “It has been shown to reduce bronchial inflammation associated with asthma in previous clinical studies, and we are currently pursuing a clinical study to assess whether it can reduce the severity of COVID-19 infection.”

RELATED CONTENT

Watch: The Future of Alzheimer’s and Dementia
Presented by the Krembil Brain Institute and the Alzheimer’s Society of Canada on September 21, 2020 – World Alzheimer’s Day – the virtual event The Future of Alzheimer’s and Dementia showcased the work of Dr. Weaver and his colleagues, who spoke live about their efforts combating Alzheimer’s disease and its associated diseases, as well as the impact of COVID-19 on these patients. You can now watch the broadcast on YouTube.