Tag: 5/12/24

Deep Depletion of Blood Lipoprotein(a) Levels with New Drug

Image by Scientific Animations, CC4.0

In a new study, researchers found that a new drug under development, zerlasiran, depleted levels of lipoprotein(a) by more than 80% in participants with increased cardiovascular risk. The drug was well tolerated and the findings, published in JAMA Network, suggest that this could be the first viable treatment for elevated levels of lipoprotein(a).

Elevated levels of lipoprotein(a) (LPa) – a type of cholesterol – is a genetic risk factor for cardiovascular disease. Present in 20% of the population, it increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Currently, there are no interventions which can bring down high LPa levels: it is unresponsive to diet, exercise, and other lifestyle changes and there is no available drug.

Zerlasiran, a small-interfering RNA that targets synthesis of LPa serum concentration, was developed to fill this gap. It is effectively a gene silencer that shuts down LPA, a gene which produces a protein found only in LPa. This in turn is expected to reduce cardiovascular risk.

A phase I clinical trial had shown that zerlasiran was safe and effective.

For the study, researchers enrolled 178 patients (average age 63.7 years, 46 female) with ASCVD and LPa concentrations greater than or equal to 125nmol/L. They were randomised to subcutaneously receive zerlasiran 300mg or 450mg, or a placebo, every 16 or every 24 weeks. The least-squares mean placebo-adjusted time-averaged percent change in LPa serum concentrations was −85.6%, −82.8%, and −81.3% for the 450mg every 24 weeks, 300mg every 16 weeks, and 300 mg every 24 weeks groups, respectively. The most common adverse events were injection site reactions, with mild pain occurring in 2.3% to 7.1% of participants in the first day following drug administration. There were 20 serious adverse events in 17 patients, none considered related to the study drug. For the group receiving a 300mcg dose every 16 weeks, it was found that even at the 60 week follow-up, 28 weeks after the last administration, that lipoprotein(a) serum concentrations were still 60% lower than baseline.

Pregnancy Enhances Natural Immunity to Block Severe Flu

Photo by Anna Hecker on Unsplash

McGill University scientists have discovered that pregnancy may trigger a natural immunity to boost protection against severe flu infection. Contrary to the common belief that pregnancy increases vulnerability to infections, researchers found that it strengthened an immune defence in mice, blocking the Influenza A virus from spreading to the lungs, where it can cause severe infection.

Our results are surprising because of the current dogma, but it makes sense from an evolutionary perspective,” said co-lead author Dr Maziar Divangahi, Professor in McGill’s Faculty of Medicine and Health Sciences and Senior Scientist at the Research Institute of the McGill University Health Centre (The Institute).

“A mother needs to stay healthy to protect her developing baby, so the immune system adapts to provide stronger defenses. This fascinating response in the nasal cavity is the body’s way of adding an extra layer of protection, which turns on during pregnancy.”

Exploring benefits for pregnancy and beyond

The researchers used a mouse model to observe how a certain type of immune cell activates in the nasal cavity of mice during pregnancy, producing a powerful molecule that boosts the body’s antiviral defenses, especially in the nose and upper airways.

“Influenza A virus remains among the deadliest threats to humanity,” said first author Julia Chronopoulos, who carried out the research while completing her PhD at McGill. “This natural immunity in pregnancy could change the way we think about flu protection for expectant mothers.”

The Public Health Agency of Canada recommends pregnant women and pregnant individuals get the flu vaccine, as they are at high risk of severe illness and complications like preterm birth. The new insights offer promise for more targeted vaccines for influenza, which is among the top 10 leading causes of death in Canada.

“The broader population could also benefit, as our findings suggest the immune response we observed could be replicated beyond pregnancy,” said co-lead author Dr James Martin, Professor in McGill’s Faculty of Medicine and Health Sciences and Senior Scientist at the RI-MUHC. This could mean new nasal vaccines or treatments that increase protective molecules, known as Interleukin-17.

The team’s next focus is on finding ways to reduce lung damage during viral infections like the flu or COVID. Rather than targeting the virus, as previous research has done, they aim to prevent dysregulated immune systems from overreacting, an approach that could lower the risk of serious complications associated with flu infection.

Source: McGill University