New strategies for ms-based metabolomics
Dr Roberta Pastorelli - IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
Post-arrest cardiac syndrome is a very complex situation, it’s a very dramatic physiopathological condition that is a consequence not only of the cardiac arrest but also of the treatment of the cardiac arrest. So this means that reperfusion, reoxygenation of the patient and this treatment can really worsen the already dramatic outcome. The majority of patients die actually from heart failure, recurrent cardiac arrest and myocardial dysfunction in the first 24 hours to 72 hours. Then there is another aspect that is very dramatic that is the neurological impairment and there is this neurological derangement in these patients that can really affect not only their survival but, in the case they are out of hospital, really their life.
What is your lab specifically working on?
It’s focussed on the use of omics tools like proteomics and metabolomics for helping in biomarker discovery, identifying novel targets of intervention and of also elucidation now for pathogenic mechanisms in different diseases, in different areas of biomedical research like neurodegeneration, cardiovascular and cancer. We got involved in this, just say, cardiovascular area a few years ago through a European project and that was very interesting because we found that the use of omics and all the advantages of knowledge that can be provided by the use of these techniques, then the conceptual framework of these techniques, they weren’t present in this setting of very fragile patients in the ICU where the management is very difficult because the lack is that you do not have factors that can predict very early what will be the outcome of these patients. For the MD really in the ICU sometimes it’s toss a coin and then to make a choice.
What metabolomics techniques are you using?
It’s been a lot of work and we are using different techniques, in terms of metabolomics different techniques. We were thinking that finding a panel of circulating metabolites could be very helpful because metabolomics can give you information about the phenotype, so the response, the final response, of a system of an organism. So we tried to move along what is the biomarkers pipeline from the discovery using preclinical models and it was very important the team collaboration. We had collaboration with our cardiovascular department, that was fundamental because they have preclinical models of, in that case, cardiac arrest, and then we move along the verification and the validation phase that’s very important for the biomarker discovery because they have access to a patient cohort. So that was possible to find that what we discovered in an animal model could have a possible meaning and a possible or putative clinical utility.
Do you think metabolomics will expand in the clinical setting?
Yes, metabolomics has a good chance to help in clinical and can move to clinics because of its own meaning. It’s the chance to look at the phenotype, so the response, to gather all the different characteristics of an individual – the genetics, the stimulus from the environment, just let’s say diet and use of drugs and everything. So they can really gather these they can really give information what is going on. And because of that there is a good chance that it’s possible to find biomarkers but, as any other omics science, it then has to face the validation. That’s the main constraint. There are a lot of papers right now and a lot of information about the putative very useful panels of biomarkers but then you have to go into cohorts. That is very expensive, of course, it’s very difficult to organise that, to have multicentre cohorts and it’s a lot of effort in terms of human resources, technologies and something like that. Also there is probably one of the limitations that hopefully will be a future trend of metabolomics that to move into the clinic it has to be more quantitative in order to provide to clinicians real treasure. This doesn’t mean like the cholesterol but it’s very important that metabolomics will have also more quantitative information to have some reference values for which you can choose what to do.
