Meet the Scientists: Dr Neil McGregor

by Sasha Nimmo

Dr McGregor is part of the research group preparing to publish ‘Biomarkers in Chronic Fatigue Syndrome’ and the data is being presented at the IACFS conference in October 2016. Until recently the group were the only researchers who used metabolomics to study ME/CFS (Canadian Consensus Criteria).

Dr McGregor was one of the editors of the Journal of Chronic Fatigue Syndrome and became involved in study of the syndrome. He was a coinvestigator and coauthor on studies with ME/CFS researchers such as Kenny De Meirleir, Dan Peterson and others.

Your paper confirms distinct biological changes, will this change how the majority of GPs treat patients?
Yes, is does identify the biological basis of the development of widespread pain. This paper should be one paper that will start to allow medical practitioners to better understand the mechanisms behind symptom development in fibromyalgia and ME/CFS or for that matter all inflammatory driven chronic disease. Until a study actually finds the cause of problem it makes it impossible to translate the findings into a valid clinical assessment. I feel this and the studies our research team are currently writing up will change the ability of clinicians to assess their patients.

Why are renal changes so important to monitor?
ME/CFS and fibromyalgia are inflammatory mediated syndromes and this is important to understand as we have found that the inflammation plays a significant part in the altering the normal renal function. Wide spread pain subjects lose amino acids through their kidney every time there is an increased inflammatory response and the frequent repetitive inflammatory response results in them gradually becoming depleted in amino acids. This is critical in the ability to convert our DNA into the enzymes required to run our cells, a process called DNA translation. The fall in urea identified in this paper not only is a result of the fall in available amino acids but also urea is used in the kidney to concentrate the urine. As the urea levels fall the ability of the kidney to concentrate urine also falls. Whilst taking amino acids may reduce the symptoms, unless we can get rid of the driver of the inflammatory response we are unlikely to be able to solve the problem properly. This alteration in renal function applies to all inflammatory driven chronic disease, which is why it is so important to understand.

The selection of the patient cohort is a problem with many studies in this field, how has the careful patient selection benefited this study?
The patients in the studies we do are selected by the clinicians involved in the projects and these have been based largely upon the Canadian criteria, although some of our earlier studies used other definitions. These clinicians run medical practices which only see ME/CFS patients which means of ability to obtain good samples, that meet the criteria, is less of a problem than we would experience if we obtained patients from general practices. These clinicians are integral partners in the research team. Their role will increase as we identify more biological events as they will be involved in the research to develop therapies.

What criteria do you use to select patient cohorts and why? 
The Canadian criteria mostly. There have been several attempts to define the ME/CFS cohort and I was an author on a paper where we evaluated the difference between a number of definitions. As one of the editors of JCFS I was involved in the acceptance and publication of the original Canadian criteria. I think it important that certain validated questionnaires are used in studies to identify subgroups within the ME/CFS cohort. It is a syndrome and therefore may have multiple causes and or genetic susceptibilities that can be identified if the data is evaluated properly.

What did you find particularly interesting about this study?
Whilst this study has interesting findings it was a reproduction study from one we published earlier. The findings were essentially the same but also gave us greater insight into the issues involved as it allowed us to extend our knowledge of the process. It is important to be able to reproduce the findings in a second study so that we know the findings are validated and not just a chance finding. This gives the clinicians and other scientists that read the paper added confidence in accepting its findings.

What are you working on at the moment?
We have just completed writing up several other papers from the metabolome/ microbiome study we collected information on a few years ago. It has taken some time to adequately address the information so we understood what we had observed. The first paper on the changes in glycolysis was published last year and the wide spread pain paper just recently. A paper on the faecal metabolome and microbiome has been submitted for publication. We are currently writing up papers on the metabolic changes associated with post exertion fatigue/malaise and a gene study based upon the findings of the post exertion paper. There are also quite a number of additional papers we will be publishing from that study.

With your background in dentistry, what led you to work in this field?
As a dentist I was consulted by patients seeking attention for face pain. What I learnt was that very little of the research seemed to be based upon sound science and was largely heresay opinions. I went to Uni of Queensland and did my specialty qualification and several years later did my PhD on pain in the facial region. What we learnt from that was that face pain Temporomandibular dysfunction syndrome has a biological basis and it part of a whole body set of changes and not a localized event. As many ME/CFS patient have this condition, as shown in the widespread pain paper, I became interested in ME/CFS. I have been privileged to be a coinvestigator and coauthor on studies with ME/CFS researchers such as Kenny De Meirleir, Dan Peterson and others. I was one of the editors of the now replaced Journal of Chronic Fatigue Syndrome and have become highly involved in study of the syndrome.

Why is your work important?
Up until recently we were the only researchers who used metabolomics to study ME/CFS and for that matter chronic pain syndromes. Other research groups have started to use these technologies but like all research it takes time to really understand the data one is evaluating. I have been involved in metabolomics research prior to the name being coined and have learnt a considerable amount about the science and how to interpret the results. It is only now that we have the knowledge base to apply to this research. Whilst many other researchers may obtain metabolomics data they will have to spend a considerable time to understand it before they can understand it and it turn apply the knowledge to its interpretation.

How is technology changing research for this illness?
The last 10 years has seen the reduction in prices for the previously highly expensive research tools such as Gas chromatography (GC), High performance liquid chromatography (HPLC), Nuclear magnetic resonance (NMR) and wide ranging genome testing. These have and will continue to change our ability to study ME/CFS. The real issue is having scientists who can understand the results produced by this technology.

Are you getting enough financial support for research? I ask because the NHMRC hasn’t funded a study into ME or CFS since 2005.

The answer is NO – not enough research dollars. To me it is important that the research dollar is wisely spent to maximize its outcome. Most of the research has been funded through philanthropic groups such as the Judith Mason and Harold Stannett Williams foundation and from donations from sufferers. I would like to take this opportunity to thank all of you so much for supporting us over the years. Without this support we would not have been able to do what we have.

Is Melbourne, and Australia, a good place to be a researcher?
We have the Bio21 institute at the University of Melbourne that gives us access to very high technology instruments – an invaluable resource. Unfortunately, Australia is not as good a place to get research funding as Europe or the US which is a significant draw back.

Given the evidence, do you believe it is time to stop recommending graded exercise therapy to people diagnosed with CFS or ME?
I would like to make a comment about this later as we have written a couple of papers to be published which address the underlying biological issues involved in the process of post exertional fatigue/malaise and its potential relationship to the exercise process. The data is being presented at the IACFS conference in October 2016 and hopefully submitted for publication prior to that date.

What are you most proud of in your career?
I have always been driven by curiosity, “the need to know how something works”. As a child I used to take radios and many other items apart to know what was in them and then put them back together. I will go to considerable lengths to understand the mechanisms behind a condition and hopefully gain knowledge that is a benefit to others. I am proud of what I have already achieved but have not finished yet.

What would you like to achieve in your career?
As a periodontist, to provide the best evidence based treatment to my patients. As a researcher I want to contribute to finding the mechanism behind pain development and the mechanisms of the development of ME/CFS and other related syndromes.

What do you enjoy outside work?
Family and friends. I paint and draw, and do photography. Have renovated many houses and built and restored furniture. There are not enough hours in the day to do what I like doing.