Identifying what causes an MS lesion

Summary

Dr John Parratt is the recipient of MS Research Australia’s inaugural Junior Practitioner Fellowship. Dr Parratt is valuable clinical researcher who has both an in-depth clinical understanding of MS and its treatment and scientific training at a PhD level.

In particular, Dr Parratt’s interests and skills in epidemiology, clinical, molecular and pathology of MS represent the integrated approach that is necessary to unravel the complexities of MS.

This Fellowship enables Dr Parratt to pursue clinical research in parallel to his clinical practice, 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-producing factories appear 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.

This young and respected clinical researcher has accumulated 10 years of scientific and medical training. MS Research Australia is pleased to support Dr Parratt’s further research goals through this fellowship which ensures the close alignment of research with the clinical goals to improve the diagnosis and treatment of MS.

Project Outcomes

Over the course of this Fellowship so far, Dr Parratt has been pursuing a number of important lines of research, particularly in relation to the self-directed antibodies (auto-antibodies) that play a role in the pathology of MS. He is also aiming to characterise different sub-types of MS particularly in relation to the ethnic background and migration status of people with MS. These programs and Dr Parratt’s other studies are summarised below.

Migrant Investigations of the Determinants of Multiple Sclerosis

A major epidemiological study entitled “Migrant Investigation of the Determinants of Multiple Sclerosis (MIDAS)” is being coordinated by Dr Parratt through the George Institute, University of Sydney and all the major MS centres in the city. To date, 1600 patients with MS have been identified and clinical and demographic data obtained with a further 1700 to be identified over the coming year. The study will determine, for the first time, the frequency of MS in different patients according to ethnicity and place of birth. This will lead to more detailed analysis on the genetic and environmental contributions that make MS what it is in any given individual.

Phenotypic analysis of Multiple Sclerosis

As part of the MIDAS study Dr Parratt has studied 200 people with MS to develop new methods to characterise and describe different sub-types of MS based on where the lesions occur in the brain and spinal cord. This is important because the areas in which lesions occur appear to be associated with the type of neurological problems and the development of disability.

Immunological characterisation of MS

Dr Parratt and his laboratory team are also examining the immune system profiles and auto-antibodies that may be associated with these subgroups of MS. It is anticipated that this may lead to better understanding of the mechanisms behind MS in different groups and refine treatments for particular groups, accordingly. The team has refined the analysis to determine that three antibodies appear to be specific for MS but occur at relatively low frequency. There are also many more antibodies that occur in only one or two individuals with MS. To determine which antibodies are important and understand how the different antibodies contribute to the development of MS, Dr Parratt’s team is developing an “Antibody Map” to establish the major targets of the immune system in the brain and spinal cord.

Viral Studies in MS

Dr Parratt has been collaborating with Professor Howard Lipton at the University of Chicago to identify specific viruses in post-mortem brain tissue from MS and MS-sister disease, Neuromyelitis Optica (NMO). This work is continuing and may provide some evidence to support the theory that virus infected B cells located just outside of the brain may contribute to the development of disease.

Choroid plexus in MS

The choroid plexus is a vital structure in the brain that produces the spinal fluid. The fluid provides nutrients to nervous system cells and removes waste products. Dr Parratt and his team have been investigating inflammation in the choroid plexus in MS and NMO to determine whether it plays a role in the pathology of MS. This study is designed to determine the extent and type of destruction that occurs in the choroid plexus in MS and how it differs from ageing and other diseases.

Publications

A new era in the treatment of Multiple Sclerosis in Australia. Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, Hodgkinson S, Kermode AG, Lechner-Scott J, Macdonell R, Marriott M, Mason DF, Parratt JDE, Reddel S, Shaw C, Slee M, Spies J, Taylor BV, Carroll W, Kilpatrick TJ, King J, McCombe P, Pollard JD, Willoughby E. 2014. Medical Journal of Australia (In press).
Sriram P, Wang C, Yiannikas C, Garrick R, Barnett M, Parratt JDE, Graham S, Arvind H, Klisthorner A. Relationship between Optical Coherence Tomography and electrophysiology of the visual pathway in non-optic neuritis eyes of Multiple Sclerosis patients.2014. PLOS one (In press).
Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective Part 1 – Historical and established therapies. Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, Hodgkinson S, Kermode AG, Lechner-Scott J, Macdonell R, Marriott M, Mason DF, Parratt JDE, Reddel S, Shaw C, Slee M, Spies J, Taylor BV, Carroll W, Kilpatrick TJ, King J, McCombe P, Pollard JD, Willoughby E. 2014. Journal of Clinical Neuroscience (In press)
Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective Part 2 – New and Emerging therapies, and efficacy. Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, Hodgkinson S, Kermode AG, Lechner-Scott J, Macdonell R, Marriott M, Mason DF, Parratt JDE, Reddel S, Shaw C, Slee M, Spies J, Taylor BV, Carroll W, Kilpatrick TJ, King J, McCombe P, Pollard JD, Willoughby E. 2014. Journal of Clinical Neuroscience (In press)
Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective Part 3 – Treatment practicalities and recommendations. Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, Hodgkinson S, Kermode AG, Lechner-Scott J, Macdonell R, Marriott M, Mason DF, Parratt JDE, Reddel S, Shaw C, Slee M, Spies J, Taylor BV, Carroll W, Kilpatrick TJ, King J, McCombe P, Pollard JD, Willoughby E. 2014. Journal of Clinical Neuroscience (In press)
Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions. Klistorner A, Sriram P, Vootakuru N, Wang C, Barnett MH, Garrick R, Parratt JDE, Levin N, Raz N, Van der Walt A, Masters L, Graham SL, Yiannikas C. Neurology. 2014 Jun 17;82(24):2165-7.
Smith A, Matthews Y, Kossard S, Turner J, Buckland ME, Parratt JDE. Cutaneous lesions in a CLIPPERS patient: further confusion between CLIPPERS and grade 1 lymphotoid granulomatosis. 2014. Journal of Cutaneous Pathology. (In Press).
Latency of multifocal visual evoked potentials in nonoptic neuritis eyes of multiple sclerosis patients associated with optic radiation lesions. Alshowaeir D, Yiannikas C, Garrick R, Parratt JDE, Barnett MH, Graham SL, Klistorner A. Invest Ophthalmol Vis Sci. 2014 May 15;55(6):3758-64. doi: 10.1167/iovs.14-14571.
Risk of relapse phenotype recurrence in multiple sclerosis. Kalincik T, Buzzard K, Jokubaitis V, Trojano M, Duquette P, Guillermo I, Girard M, Lugaresi A, Grammond P, Grand'maison F, Oreja-Guevara C, Boz C, Hupperts R, Petersen T, Giuliani G, Iuliano G, Lechner-Scott J, Barnett M, Bergamaschi R, Van Pesch V, Amato MP, van Munster E, Fernandez-Bolanos R, Verheul F, Fiol M, Cristiano E, Slee M, Rio ME, Spitaleri D, Alroughani R, Gray O, Saladino ML, Flechter S, Herbert J, Cabrera-Gomez JA, Vella N, Paine M, Shaw C, Moore F, Vucic S, Savino A, Singhal B, Petkovska-Boskova T, Parratt JDE, Sirbu CA, Rozsa C, Liew D, Butzkueven H; on behalf of the MSBase Study Group. Mult Scler. 2014 Apr 28. [Epub ahead of print]
Neurotropic T-cell lymphocytosis: a cutaneous expression of CLIPPERS. Smith A, Matthews Y, Kossard S, Turner J, Buckland ME, Parratt JDE. J Cutan Pathol. 2014 Mar 18. doi: 10.1111/cup.12344. [Epub ahead of print]
Characterisation of a syndrome of autoimmune adult onset focal epilepsy and encephalitis.Ramanathan S, Bleasel A,Parratt JDE, Orr C, Dale RC, Vincent A, Fung VS.J Clin Neurosci. 2014 Jul;21(7):1169-75. doi: 10.1016/j.jocn.2013.09.024. Epub 2013 Dec
Ha AD, Parratt JDE, Babu S, Kim SD, O’Neill J, Halpern JP, Fung VS. Movement Disorders associated with CLIPPERS. Movement Disorders. Nov 2013. (Epub ahead of Print).
Kaushik M, Wang CY, Barnett MH, Garrick R, Parratt JDE, Graham SL, Sriram P, Yiannikas C, Klisthorner A. Inner Nuclear Layer Thickening is Inversely Proportional to Retinal Ganglion Cell Loss in Optic Neuritis. PLOS one. Oct 2013. 3: 8 (10)
Femia G, Parratt JDE, Halmagyi GM. Isolated reversible hypoglossal nerve palsy as the initial manifestation of pre-eclampsia. J of Clin Neuroscience. Nov 2013. 20:11; 1608-1610.
Simon NG, Parratt JDE, Barnett MH, Buckland ME, Gupta R, Hayes MW, Masters LT, Reddel SW.Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):15-22.
Barnett M, Prineas J, Buckland M, Parratt JDE, Pollard J.Massive astrocyte destruction in neuromyelitis optica despite natalizumab therapy. Mult Scler. 2012 Jan;18(1):108-12. Epub 2011 Aug 25.
Prineas JW, Henderson AP, Barnett MH, Parratt JDE. Multiple Sclerosis as an ‘inside-out’ disease. Ann Neurol. 2010 Nov.68 (5); 768-768.
Parratt JDE, Prineas JW.Neuromyelitis optica: a demyelinating disease characterized by acute destruction and regeneration of perivascular astrocytes. Mult Scler. 2010 Oct;16(10):1156-72. Epub 2010 Sep