TIA supports bid to overcome leading cause of hospital ICU deaths

TIA facilities are core to research into a targeted therapeutic to overcome sepsis, a leading cause of death in hospital intensive care units.

TIA’s Australian Translational Medicinal Chemistry Facility (ATMCF) at Monash Institute of Pharmaceutical Sciences has been used to study and refine compounds that show promise as a drug candidate for inflammation, primarily for people with sepsis.

The project involves leadership from Australian National University Professor Philip Board, alongside ATMCF Director Professor Jonathan Baell.

Source: Australian Translational Medicinal Chemistry Facility

Professor Baell said infection caused sepsis, which in turn could result in life-threatening inflammation.

When inflammation was combined with blood clotting in people with sepsis, blood flow reduced to vital organs, causing organ failure and even death, Professor Baell said.

Inflammation was a part of the body’s complex protective response against bacteria, tissue damage or irritants, he said.

“Inflammation is a natural immune response, but it has to match the size and scope of the issue that the body is protecting against.

“For example, too little inflammation is a problem because it doesn’t adequately stop a bacterial infection and too much is also serious for because it can reduce blood flow to limbs and vital organs.”

Sepsis a leading cause of death in hospital intensive care units, with between 20 and 30 per cent of sepsis patients dying – some in as little as 24 hours.Present treatments supress the entire immune system and leave patients at greater risk of infection and serious complications from side effects. No new medicines have been developed in the past 30 years.

At the core of Professor Baell’s research is a method to block an enzyme that plays a critical role in inflammation.

“There are only 22 molecules have been reported to block the enzyme and we have whittled that down to two as potential therapeutics that we want to study further. Our research will focus on predicting how each of the molecules will impact the body’s biological processes, and then aim to refine them. We want to make sure we have the best and most potent drug candidate as possible before we move into preclinical trials that focus on safety and efficacy.”

Professor Baell’s team used expertise in drug design, synthetic chemistry methods and structure activity relationships – used to predict biological activity – to conduct a thorough analysis at ATMCF and provide proof of concept ahead of preclinical trials.

OmegaOne Therapeutics, a partnership between Monash and the Australian National University, has secured $500,000 from national biomedical incubator CUREator, managed by Brandon BioCatalyst, for further studies.

“Chronic inflammation has the potential to increase the risk of various diseases, so with these funds the team will be looking further into validating small molecules as a new therapeutic strategy,” Professor Baell said.

“This can prevent inflammation caused by a wide range of common non-infectious diseases, without toxic side effects or weakening the patient’s immune system.

“Our ultimate aim is a safe and effective treatment for acute bacterial sepsis that can be dissolved in liquid for intravenous administration in a hospital.”

The research has an initial focus on sepsis, but the molecules being studied may also prove beneficial for people with heart disease, type 2 diabetes, Parkinson’s disease and even severe asthma, Professor Baell said.