Identifying obesity-related health issues before they become critical

New weight loss drugs may help tackle the global obesity crisis, but the scale of the problem is such that millions of people may still develop obesity-related health complications such as heart and liver disease.

There is currently no reliable way of identifying either those at risk of developing complications or those in the early stages of liver disease (when the damage is still reversible) and this deficit prompted Dr Fiona McGillicuddy, assistant professor of medicine at UCD, to channel her two decades of obesity and heart disease research into developing solutions for both.

The MetHealth risk stratification platform identifies those likely to develop metabolic-related health complications while a highly specialised blood test can indicate early stage liver disease a lot more accurately than conventional markers such as cholesterol and glucose.

The risk stratification platform is close to launch. The liver disease blood test is in late stage development.

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“Obesity is rapidly becoming the leading cause of liver transplants in western society yet the only way to clinically diagnose early (inflammatory) stage liver disease is through invasive biopsies, which are notoriously unreliable and are being phased out due to their associated risks,” Prof McGillicuddy says.

“That said, early identification of and aggressive intervention with the highest risk patients is a priority because it would limit the development of costly and life-limiting complications.”

The beauty of MetHealth’s solution is that it’s based around a simple blood test. Once the sample is taken, however, that’s when the complex science kicks in to accurately measure more than 80 proteins attached to the body’s “good” or HDL cholesterol. Measuring HDL particles gives clinicians a good insight into how healthy someone’s liver is.

“The HDL proteome is an extremely sensitive biomarker and our data to date indicates that the HDL proteome may serve as an early indicator of liver disease in patients with obesity,” Prof McGillicuddy says. “However, our ability to harness the powerful potential of HDL particles has been limited by the complexity of isolating HDL from serum as well as the lack of a high-throughput test that can accurately measure all the proteins. Our solution involves a new method of isolating HDL in an affordable and high-throughput manner.

“Secondly, the data shows that people who progress to a more metabolically unhealthy obese state have increased pro-inflammatory proteins, and loss of antioxidant and anti-inflammatory proteins on their HDL particles. By using a machine learning approach to process this data, we were able to create a scoring algorithm that can accurately stratify patients with obesity who are at most risk.”

An estimated 2.1 billion people worldwide are either overweight or obese making for a potentially huge global market for MetHealth’s products. Those expected to show an early interest are clinicians, pharma companies, academics and the food industry.

“Our solution is significant not only for liver disease but also because it has applications in heart disease, stroke and certain forms of cancer.

“We are also considering a B2C [business-to-consumer] route whereby those interested in checking their metabolic health can have this test done,” Prof McGillicuddy says, who adds that the platform can also be used to track metabolic health status if a patient starts a new treatment (such as a different medication) and in the functional food space to establish if foods that claim to have particular health benefits actually do, based on hard scientific evidence.

MetHealth is expected to spin-out in the second quarter of next year with the support of Nova UCD’s innovation hub.

To date the project has received €585,000 in funding from Enterprise Ireland and Science Foundation Ireland while early research into what has become MetHealth was supported by Prof McGillicuddy’s €750,000 Wellcome Trust fellowship. MetHealth is adequately funded for now but will be looking to raise a seed round of €2.5 million when the spin out is complete out in roughly a year’s time.