The Development of Targeted Proteomic Assays, Attempting to Take Biomarkers from the Research Lab to the Clinic

Kevin Mills
University College London

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Kevin Mills (Presenter) University College London

Presenter Bio: I am an Associate Professor at UCL, Honorary Clinical Scientist at Great Ormond Street Hospital (GOSH) and Head of the Translational Mass Spectrometry Research Group at the UCL Institute of Child Health. My research group's aim is to bring together state-of-the-art mass spectrometry with precision and stratified medicine, to find new drug targets, disease mechanisms, identify new biomarkers and develop new and more precise tests for the NHS.We mainly use the techniques of proteomic, metabolomic and lipidomics for hypothesis generating and biomarker discovery research, followed by validation and translation onto triple quadrupole mass spectrometry based platforms. My main research interest involves using these techniques to understand the disease mechanisms underlying neurological and rare inborn errors of metabolism.

Relevant Financial Disclosures (within past 24 months) Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

The development of targeted proteomic assays, attempting to take biomarkers from the research lab to the clinic.

Almost all large hospitals have LC-triple quadrupole based mass spectrometry platforms. These robust and versatile instruments are used for a multitude of small molecule analyses including amino acids, glycosphingolipids, glucosaminoglycans, vitamins as well as for monitoring immunosuppressant levels, drug trials and neonatal screening for inborn errors of metabolism. However, rarely are these instruments used in a clinical setting for the analyses of proteins and are usually analysed using immunochemistry based assays (ELISA, radioimmunoassays etc).

LC-MS based analyses, particularly with stable isotope labelled internal standards, are unparalleled for their accuracy and assay reproducibility with intra- and inter-assay coefficients of variations of often less than 2% and 5-8%, respectively. This is substantially lower than that of many immunochemistry based protein assays which often have intra- and inter-assay based coefficients in the range of 10-25%. Therefore, it is logical to try to combine the accuracy and reproducibility of LC-MS based platforms to analyse proteins in a clinical setting. This type of analysis has other added advantages over immuno-based technology including;

• Cost implications (no need to purchase kit based systems from a third party)
• Multiplexing up to 50-80 proteins in a single analysis
• Validation of biomarkers from discovery experiments
• the ability to translate biomarkers into routine tests in a clinical setting much quicker than having to wait for the development to market of a kite marked kit.

The work of my research group attempts to bridge the gap between finding a biomarker in a research lab to its validation and potential translation of that test into a clinical setting. I will give several examples of this where we have found biomarkers in plasma, urine and CSF and translated them into multiplexed tests. The diseases I will cover will include inborn errors of metabolism (Fabry Disease), hypertrophic cardiomyopathy and the neurodegenerative conditions of Alzheimer’s and Parkinson’s disease.