Dr John Parratt
$320,000 over 2010 - 2014
Dr John Parratt is the recipient of MS Research Australia’s inaugural Junior Practitioner Fellowship. He is a highly respected and talented clinician and researcher and represents a unique and valuable breed of clinical researchers that have both an in-depth clinical understanding of MS and scientific training at a PhD level.
In particular, Dr Parratt’s interests and skills in the epidemiology, clinical, molecular and pathological aspects of MS represent the integrated approach that is necessary to unravel the complexities of MS.
With this fellowship, Dr Parratt has the security and opportunity to undertake further clinical and scientific work to advance specific goals including:
- Identify and understand the development of newly forming lesions in MS
- Identify early and MS specific molecular changes in the brain
- Understand why myelin production appears to be compromised in the early stages of MS lesion formation
Overall, Dr Parratt’s work will identify, describe and explain the pathogenesis of acute MS lesions. The results have the capacity to improve and create better treatments for people with MS.
Progress to Date
Dr Parratt is developing a multi-modal method to identify the targets of the immune response in MS. The first step of this project is an effort to categorise people with MS into groups depending upon the clinical features of the disease in each individual case. To do this, Dr Parratt has developed new clinical and radiological criteria and set up an internationally-linked MS epidemiology study with the George Institute and the University of Sydney.
The epidemiological study, called MIDAS (Migrant Investigation of the Determinants of Multiple Sclerosis), will attempt to identify everyone with MS in Sydney and determine the ‘type’ of MS that they have according to the new criteria. The study will also examine MS amongst infrequently studied ethnic groups, particularly Indian and Chinese people. Dr Parratt will compare the characteristics of the disease in people from these ethnic groups who live in Sydney with people who do not migrate. This major international study involves collaborators in Mangalore (India), Shanghai (China) and Vancouver (Canada) and is the first study of this type worldwide. Not only will the MIDAS study help to characterise MS in large multi-ethnic populations in Australia, but it will also provide information on the burden of disease in these groups of people. It will also provide the ideal platform for future investigative studies into novel risk factors. The collaboration within Sydney has been established and eight major MS centres will participate. Recruitment of people with MS for the Sydney-based work is now underway.
To identify the pathological processes that exist in patients with specific types of MS, Dr Parratt has developed a novel laboratory method to identify antibodies in the blood of patients with MS and other neurological conditions (in association with Prof John Prineas, University of Sydney). This new method will reveal much about the pathogenesis of the disease and is considered by Dr Parratt to be ‘the most exciting avenue of MS research to date’. Three preliminary reports will be published in the next six months. Additional work has begun on characterising the targets of these antibodies and how they may damage the brain and spinal cord in MS.
To determine whether antibodies that are found in the blood of people with MS are relevant, Dr Parratt is also looking at brain tissue that has been affected by MS. Dr Parratt and colleagues have completed the largest study of myelin ever undertaken on autopsy cases of MS. This work will be published in a prestigious international journal, the Annals of Neurology, during 2012. From this exhaustive study, Dr Parratt has made a number of discoveries regarding how a MS lesion forms in the brain or spinal cord. Dr Parratt’s work shows that myelin destruction in MS is secondary to damage to the myelin producing cell, the oligodendrocyte. He has also shown that the death and damage seen in oligodendrocytes is the same, irrespective of the size, type or location of the lesion in the brain.
Dr Parratt has also compared MS lesions with the damage seen in a sister disease known as neuromyelitis optica (NMO). In NMO, damage first occurs in brain support cells, known as astrocytes, with damage to the oligodendrocytes occurring later. Dr Parratt and colleagues believe that in MS, the first cell affected may also be the astrocyte, or some similar element in the tissue, with secondary damage to the oligodendrocyte and later damage to the myelin. This is currently under investigation and will hopefully identify the targets of the immune system in MS and allow the development of new, highly specific therapies.
Prineas JW and Parratt J. (2012) Oligodendrocytes and the early MS lesion. Annals of Neurology DOI: 10.1002/ana.23634