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In treating sepsis, Lawson researchers find promise in carbon monoxide-releasing molecules

Courtesy: Lawson Health Research Institute

Scientists at London’s Lawson Health Research Institute are studying the promising use of carbon monoxide-releasing molecules in the treatment of sepsis, the potentially fatal condition wherein the body overreacts to an infection, leading to an overwhelming inflammatory response.

That inflammatory response from sepsis, triggered by microbial pathogens such as a virus, bacterium or fungi, can spread through the body causing damage to organs such as the heart, liver, lungs or brain.

Researcher Dr. Gedas Cepinskas says that with sepsis, the immune system becomes so activated that it attacks cell tissues, resulting in damage to affected organs.

“Unfortunately, there is no specific therapy or treatment. It is well-accepted, the use of antibiotics, fluids and supply of oxygen just to keep organs working. That’s why any new potential therapy in treating systemic inflammation, in general, is very desired,” Cepinskas told London Live with Mike Stubbs on Tuesday.

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“Carbon monoxide is not just the poisonous gas, but rather has very potent, protective anti-inflammatory cytoprotective characteristics,” in small, non-toxic concentrations, he notes.

Read more: COVID-19: Potential sepsis treatment moves to human trials in London, Ont.

Carbon monoxide is produced naturally by practically every cell in the human body, Cepinskas says, and is used as a defence mechanism — an “acute or early protective response against various cell-damaging signals or stresses.”

“We evolved on this idea … and we tried to use, not inhaled carbon monoxide, but rather specific molecules which are called carbon monoxide-releasing molecules or CORMs … in treating various inflammatory conditions in preclinical models,” he said.

They found success, according to a statement from Lawson, which noted a recent study published in Experimental Biology and Medicine found efficacy in using CORMs in preclinical models to “protect individual cells in the liver and lungs of sepsis-induced inflammation.”

“We were very lucky to be one of the first to demonstrate very potent anti-inflammatory effects of (CORMs) in experimental models of sepsis and even severe traumatic injuries, for example, compartment syndrome,” Cepinskas said.

“All these pathologies, compartment syndrome, sepsis, and even organ transplantation … have one common denominator or feature, which is systemic inflammation,” he added.

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According to Lawson, Cepinskas is working with LHSC clinicians to study the use of CORMs in treating limb compartment syndrome and to improve organ transplantation, and is working with the pharmaceutical industry to move the promising therapy into clinical trials.

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Meet Dr. Cepinskas, researcher at Lawson and Western University Schulich School of Medicine, Dentistry – Sep 23, 2020

According to the World Health Organization, 48.9 million cases of sepsis and 11 million sepsis-related deaths were reported around the world in 2017. Almost half of all sepsis cases that year involved children.

Diarrhoeal diseases and lower respiratory infections were the largest contributors to sepsis cases and sepsis-related deaths in 2017, linked to 9.2 to 15 million annual cases and 1.8 to 2.8 million annual cases, respectively, the WHO said. Nearly half of all deaths were due to underlying injury or chronic disease.

In Canada, just over 16,300 people died of sepsis from the start of 2015 through the end of 2019, an average of about 2,728 per year, according to the most recent data from Statistics Canada.

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Read more: What you need to know about sepsis, septic shock and stem cells

A study published late last year found that sepsis or systemic inflammation was among the most common complications associated with COVID-19, alongside pneumonia, respiratory failure, and kidney failure.

“Statistics indicate that every 2.8 seconds a person dies from sepsis globally,” Cepinskas said.

“Sepsis is one of the most expensive disease condition(s) to treat, and it costs to (the) Canadian health system $1 billion each and every year, and the expense is going up, unfortunately.”

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Health Matters: Sepsis kills more people than heart disease and cancer – Jan 17, 2020

According to the Canadian Sepsis Foundation (CSF), those at risk of developing sepsis include those 75 or older; those with chronic disease; those engaged in drug use, especially by injection; those who consume tobacco and tobacco products; and those on immunosuppressive agents like chemotherapy.

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According to CSF, the delaying of treatment for health conditions such as appendicitis, pneumonia, or even influenza may provoke an immune response leading to sepsis. COVID-19 and parasites such as malaria can also lead to sepsis.

Sepsis can also stem from infections caused by invasive procedures, like open-heart surgeries, where bacteria can be introduced directly into the bloodstream.

Symptoms may vary depending on the primary infection, but CSF says common symptoms of sepsis include an altered mental state, decreased urination, feeling extremely ill (severe pain or discomfort), fever and/or chills, and a rapid heart rate and/or rapid breathing.

Read more: July 2020: McMaster research leads Canada-wide research initiative to address sepsis

The research into carbon monoxide-releasing molecules isn’t the only work being done at Lawson when it comes to the treatment of sepsis.

A potentially groundbreaking drug more than 20 years in the making, developed by a team at Lawson led by Dr. Qingping Feng, entered clinical trials earlier this year involving local COVID-19 patients with sepsis.

The trial is looking into the effectiveness of a sepsis treatment using a manufactured form of annexin A5, a human protein believed to help counter inflammation and coagulation.

Pre-clinical studies showed promising results in treating sepsis in animal models, and in late 2020, the team reported that annexin A5 could be effective in 40 per cent of sepsis cases, a significant jump from current treatments which work roughly six per cent of the time, according to Lawson.

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— With files from Jacquelyn LeBel

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