In 2006, four researchers were awarded grants by MSIF which enabled them to travel to work on MS projects in Australia and the United States.
Lisa van Baarsen, Netherlands
Lisa G.M. van Baarsen, from the Netherlands, was awarded a £4,000 grant and travelled to the Van Andel Research Institute, in Michigan, USA for six weeks.
Lisa was trained in proteomics using antibody array technology under the supervision of Dr Brian Haab (with Lisa, right). Her studies resulted in the identification of a list of proteins that were differentially produced in patients with recently onset MS compared to healthy patients. These proteins could potentially be biomarkers for diagnosis and prognosis.
A second study found some proteins that are differentially produced between relapsing-remitting MS and secondary progressive MS. Lisa was selected to give a presentation about her work at the ISNI2006 in Nagoya, Japan, in October 2006.
Recently Published Papers
van Baarsen LG, Vosslamber S, Tijssen M, Baggen JM, van der Voort LF, Killestein J, van der Pouw Kraan TC, Polman CH, Verweij CL.
Pharmacogenomics of interferon-beta therapy in multiple sclerosis: baseline IFN signature determines pharmacological differences between patients. PLoS ONE. 2008 Apr 2;3(4)
van Baarsen LG, van der Pouw Kraan TC, Kragt JJ, Baggen JM, Rustenburg F, Hooper T, Meilof JF, Fero MJ, Dijkstra CD, Polman CH, Verweij CL.
A subtype of multiple sclerosis defined by an activated immune defense program. Genes Immunology 2006 Sep;7(6):522-31
Raoul Oude Engberink, Netherlands
Raoul Oude Engberink from the Image Sciences Institute at the Utrecht University Medical Centre (UMCU) in the Netherlands used his MSIF Du Pré Grant to work with Prof JWM Bulte at the Department of Radiology and Radiological Science at the Johns Hopkins University School of Medicine, Baltimore, USA.
The research focused on the visualisation and tracking of monocytes using magnetic resonance imaging (MRI).
Results of the research show that monocytes can be effectively labelled by magneto electroporation (MEP) using a special class of magnetic resonance (MR) contrast agents - iron oxides - without affecting cell viability and metabolic activity. The high amount of iron uptake per cell, as observed on the histological stainings, indicates that these cells can be readily detected by MRI. In comparison to other labelling techniques like simple incubation and the use of transfection agents, MEP appears to be ultra-fast and extremely efficient. Based upon in vitro data acquired at Johns Hopkins, this monocyte labelling strategy is a powerful tool for accurate tracking of monocytes by MRI in MS pathology.
Having returned to the Netherlands, Raoul continues to work on this research project in collaboration with the Utrecht University Pharmaceutical Department. He aims to transfer the learnt technique to the UMCU laboratories through the purchase of an electroporator, funded, in part, by his MSIF Du Pré Grant.
- monocyte – a white blood cell that, as part of the human body’s immune system, protects against blood-borne pathogens. Monocytes are active in central nervous system inflammation and the neurodegeneration in MS.
- magneto electroporation (MEP) – a voltage based technique that causes an increase in the permeability of the cell plasma membrane through an externally applied electrical field
International Society for Magnetic Resonance in Medicine Meeting (18-25 May 2007, Berlin)
The results of a part of Raoul's continued work with the Utrecht University - MR visualization of electroporated monocytes - will be presented at the International Society for Magnetic Resonance in Medicine (ISMRM) meeting in Berlin in May 2007.
Recently Published Papers
Vellinga MM, Oude Engberink RD, Seewann A, Pouwels PJ, Wattjes MP, van der Pol SM, Pering C, Polman CH, de Vries HE, Geurts JJ, Barkhof F.
Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement.
Brain. 2008 Mar;131(Pt 3):800-7.
Oude Engberink RD, van der Pol SM, Döpp EA, de Vries HE, Blezer EL.
Comparison of SPIO and USPIO for in vitro labeling of human monocytes: MR detection and cell function.
Radiology. 2007 May;243(2):467-74.
Helen Tremlett, Canada(pictured centre with her Australian colleagues)
The collegial and intellectual environment at the Menzies Institute greatly facilitated learning throughout the placement. Furthermore, cross-fertilisation of ideas between different disciplines within the institute, such as rheumatology, diabetes, cancer and genetics, was possible. I was able to take advantage of the wealth of knowledge and numerous contacts the MS Research Group had amassed through previous collaborative research into MS in Tasmania and across Australia.
In November 2006, a Du Pré Grant enabled Helen Tremlett from the Neurology Division of the Faculty of Medicine, University of British Columbia in Canada to travel to the Menzies Research Institute, University of Tasmania in Australia. Overseen by Prof Anne-Louise Ponsonby and Dr Ingrid Van der Mei of the Institute’s MS Research Group, Helen spent four months working on part of an ongoing three-year population-based MS observational study being carried out in southern Tasmania. The study is primarily examining whether lifestyle and environmental factors influence the progression of MS and Helen was able to use the collected data for the two projects she carried out.
Project one – Adherence in multiple sclerosis: contrasting factors affect stopping immunomodulatory therapy and missing doses
During the study both levels of non-adherence – stopping immunomodulatory drugs (IMDs) and missing doses – were examined. Little is currently known about the latter. Demographic, clinical, psychological and cognitive factors affecting adherence were examined by logistic regression and a longitudinal analysis. The influence of missed doses on clinical outcomes was then examined.
It was found that stopping IMD was associated with previous relapses and education level whilst missing doses was associated with alcohol use and a prior history of missed doses. It was concluded that adherence measures should be routinely incorporated into clinical trials, which would facilitate establishing if missed doses drives therapeutic failure or reflects a ‘healthy adherer’ effect.
A paper has been submitted for publication in a peer-reviewed journal and an abstract will be submitted to ECTRIMS in 2007.
Project two – Relationship between relapses, infection and seasonal environmental factors in MS
The relationship between infections, relapses and disease progression in MS was examined with a special emphasis on assessing the seasonality of relapses and the contributions of these factors to the seasonal pattern. Ambient climatic and atmospheric data collated by the Cardio Respiratory Group in Tasmania supported the study.
The analysis is ongoing and collaborative work on this project will continue between the Menzies Research Institute, Tasmania and the University of British Columbia.
I wish to thank MSIF for enabling me to travel to Tasmania to carry out research at the Menzies Institute. I found the whole experience very positive and highly rewarding. I intend to continue building collaborations with Tasmania that were initiated because of the Du Pré Grant.
Gabrièle Piaton, France
This training period allowed me to acquire new expertise in the tissue culture model of central nervous system (CNS) myelination. I have also gained a better overview of the complex relationships affecting oligodendrocyte (OL) cell biology, which are involved in remyelination. - an understanding of which could be relevant in the development of new therapeutic strategies promoting remyelination in disorders such as MS.
In October 2006, Gabrièle Piaton from the Institut National de la Santé et de la Recherche Médicale (INSERM U711), Hôpital de la Salpêtrière in Paris, France began an eight month research visit to the Smilow Research Center, New York University School of Medicine in the USA.
As part of the Neuroscience Program, and under the supervision of Dr James Salzer and Dr Carla Taveggia, Gabrièle was involved in a number of different projects working on the origin of remyelinating cells in the adult CNS and the identification of the signals that trigger their activation.
Gabrièle’s main projects focused on gaining a better understanding as to whether the protein type III neuregulin-1 (NRG-1), also known as CRD, might be a pro-(re)myelinating signal. Recent studies have shown that type III NRG-1 is the main effector for myelination in the peripheral nervous system (PNS) and promotes myelination in the CNS. Preliminary results suggested that NRG-1 might participate in remyelination of specific neuronal subpopulation(s), along with other factors yet unidentified.
The work on type III NRG-1 will continue at the Center.
In June 2007, Gabrièle’s team at the Smilow Research Center presented an abstract at the 13th Annual Kentucky Spinal Cord and Head Injury Research Trust Symposium.
13th Annual Kentucky Spinal Cord and Head Injury Research Trust Symposium Abstract (13 kb)