Professors Nicole Zitzmann and Raymond Dwek at the Oxford Glycobiology Institute have used proteomics techniques to identify potential novel protein biomarkers for the most common liver disorder in the Western world
Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of progressive liver disease ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH). Approximately 1 in 3 people in the UK have some degree of MASLD and most affected individuals are unaware they have the disease. Currently, the reference standard for assessing MASLD is the liver biopsy, an invasive, painful procedure which can be unreliable and costly. Consequently, there is a need for improved, minimally-invasive methods of determining stages of MASLD in patients.
Two post docs in the Zitzmann lab, Bevin Gangadharan and Abhinav Kumar, have used 2D gels and mass spectrometry to separate proteins in serum from patients with MASLD at various stages of the disease and have identified several potential biomarkers, importantly including ones which can differentiate simple steatosis from MASH.
The Zitzmann lab have successfully developed an antibody-free assay for serum apolipoprotein F (ApoF), one of their most promising MASLD biomarkers, using parallel reaction monitoring (PRM) mass spectrometry. Unlike currently used immunoassays, this approach has the potential to detect degraded proteins since the assay detects tryptic peptides instead of intact proteins.
Since MASLD affects 1 in 3 people in the UK and US, there is an urgent need for a rapid and inexpensive test to screen at risk individuals such as those who are clinically obese who have a 90% chance of having the disease. The Zitzmann lab are therefore currently looking into ways of developing a rapid point-of-care test which can determine biomarker levels from a single drop of finger-pricked capillary blood.
The novel Oxford biomarkers would allow clinicians to identify MASLD patients so they could be advised about lifestyle changes, such as diet and exercise, which could help to reverse the disease and thus save money for the NHS and other health providers. The technology could potentially be used to diagnose, prognose or monitor the progression of MASLD in an individual thereby reducing the need for a liver biopsy. These biomarkers could also help to reduce disease progression since patients could be stratified according to the stage of MASLD ensuring appropriate measurements can be taken.
This technology is at a preclinical stage and is currently being validated in a larger clinical cohort. The Zitzmann lab are currently looking for commercial partners who wish to collaborate to validate the biomarkers or licence this technology.
References
1. Bevin Gangadharan, Abhinav Kumar, Raymond Dwek, Nicole Zitzmann, Mark Thursz, Jeremy Cobbold (2018) Clinical diagnosis of non-alcoholic fatty liver disease using a panel of human blood protein biomarkers, Patent Publication Number: WO/2018/037229.
2. Abhinav Kumar, Bevin Gangadharan, Jeremy Cobbold, Mark Thursz, Nicole Zitzmann (2017) Absolute quantitation of disease protein biomarkers in a single LC-MS acquisition using apolipoprotein F as an example, Scientific Reports, 7, 12072.
