Biomarkers in paediatric CNS demyelination, and risk of progression to MS

Dr Fabienne Brilot-Turville

Westmead Millennium Institute, NSW

January 2010

specialisation: Immunology

focus area: Causes and Prevention

funding type: Incubator

project type: Investigator Led Research

Summary

MS is the most common cause of neurological disability in young adults and adolescents. This study will identify the earliest immune responses against the brain in children who develop MS. Identifying these early immune responses will allow early and directed treatments to prevent disability in the future.

The goal of this project is to understand the role of humoral immunity (B cells and antibodies) during a first episode of demyelination. Among myelin neuronal antigens, myelin oligodendrocyte glycoprotein (MOG) is thought to be one of the main targets because of its outer position on the myelin sheath, and MOG is thus accessible to antibodies.

However, detection of anti-MOG antibody in MS patients has been controversial due to technical discrepancies. Instead, we have used a novel assay, which uses cells expressing the correctly folded native MOG protein at the cell surface. The detection of anti-native MOG Ab in children will help us to define a subgroup of patients that may benefit from therapy targeting humoral immunity with the aim of preventing progression to MS.

Outcome

In a short period of time the team of young researchers, with complimentary skills in clinical neuroscience and basic science immunology, have made rapid progress in the understanding of paediatric MS. Their research has already resulted in a remarkable four publications in peer-reviewed scientific journals. ‘We are grateful for the support of The Trish Multiple Sclerosis Research Foundation and MS Research Australia’, explained Dr Brilot-Turville.

Up to 10% of adult MS sufferers have their first episode of demyelination when they are young, and MS is being diagnosed increasingly in children. A protein named MOG (Myelin Oligodendrocyte Glycoprotein) is thought to be important in the autoimmune response observed in MS. Dr Brilot-Turville and colleagues have recruited the largest Australian group of Children with a first episode of demyelination. ‘With our Incubator grant from MS Research Australia and the Trish Multiple Sclerosis Research Foundation, we have been able to show that the presence of antibodies against MOG is a sensitive indicator in a subgroup of children with their first episode of demyelination,’ reported Dr Brilot-Turville.

The researchers have also developed a new test to enable them to identify white blood cells, especially antibody-producing B cells, in the cerebrospinal fluid of patients. This is important, as B cells may be involved in the generation of MOG antibodies in children with first episode of demyelination.

These exciting developments have enabled Dr Fabienne Brilot-Turville to build on MS Research Australia and Trish Multiple Sclerosis Research Foundation funding and gain a three year Research Fellowship from the Star Scientific Foundation to continue her research.

publications

Dale RC & Brilot F. Biomarkers of inflammatory and autoimmune central nervous system disorders. Curr Opin Pediat2010; 22: 718-725 (I.F.: 2.215)
Selter RC, Brilot F, Grummel V, Kraus V, Cepok S, Dale RC & Hemmer B. Antibody responses to EBV and native MOG in pediatric inflammatory demyelinating CNS diseases. Neurology 2010; 74(21): 1711-15 (I.F.: 8.172)
Dale RC, Tantsis E, Merheb V & Brilot F. Cerebrospinal fluid B cell expansion in longitudinally extensive transverse myelitis associated with Neuromyelitis Optica IgG. Dev Med Child Neurol, accepted for publication on Feb 28th 2011 (I.F.: 3.019)
Pröbstel AK, Dornmair K, Bittner R, Sperl P, Jenne J, Magalhaes S, A Villalobos, C Breithaupt, R Weissert, U Jacob, M Krumbholz, T Kuempfel, A Blaschek, W Stark, J Gärtner, D Pohl, K Rostasy, F Weber, I Forne, M Khademi, T Olsson, F Brilot, E Tantsis, RC Dale, H Wekerle, R Hohlfel, B Banwell, A Bar-Or, E Meinl, T Derfuss. Submitted to Neurology.
Brilot F, Dale RC, Selter RC, Grummel V, Reddy Kalluri S, Aslam M, Busch V, Zhou D, Cepok S & Hemmer B. Antibodies to native MOG in children with inflammatory demyelinating CNS disease. Ann Neurol 2009; 66(6): 833-42 (I.F.: 9.317)
Ramanathan, S., Reddel, S.W., Henderson, A., Parratt, J.D.E., Barnett, M., Gatt, P.N., Merheb, V., Kurrnan, R.A., Pathmanandavel, K., Sinmaz, N., Ghadiri, M., Yiannikas, C., Vucic, S., Stewart, G., Bleasel, A.F., Booth, D., Fung, V.S.C., Dale, R.C., & Brilot, F. (2014). Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis. Neurology. 1(4) 40.

Updated: 25 February 2015

lead investigator

Dr Fabienne Brilot-Turville
Dr Russell Dale

total funding

$26,000

start year

2010

duration

1 year

STATUS

Past project

Biomarkers in paediatric CNS demyelination, and risk of progression to MS

Dr Fabienne Brilot-Turville

Westmead Millennium Institute, NSW

January 2010

specialisation: Immunology

focus area: Causes and Prevention

funding type: Incubator

project type: Investigator Led Research

Summary

Outcome

publications

lead investigator

total funding

start year

duration

STATUS

1300 010 158

info@msaustralia.org.au

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Biomarkers in paediatric CNS demyelination, and risk of progression to MS