TOMAS OLSSON GROUP
Clinical and experimental neuroimmunology
A large part of our research focuses on mechanisms involved in the disease pathogenesis of MS.
Since MS is caused by inflammation and the inflammation can be controlled, the MS disease should in principal be curable or at least preventable to a large extent. Some of the currently available therapies are in fact able to dampen the relapse rates up to 70 %. However, these therapies broadly interfere with the immune system, which is needed for the host defense against infections, and may be risky over a long term prospects. Therefore, the primary goal is to achieve a more detailed knowledge on the exact modes and mechanisms in which the immune system is allowed to attack the nervous system in order to develop much more precise therapeutic interventions.
Both environmental factors and gene variants contribute to the cause of MS. The genes involved are likely to be many (the candidate genes are around hundred today) and therefore may differ between different individuals with MS. This has been a working hypothesis for decades, but with recent technological and intellectual developments this can be properly studied.
Our General Aim is to understand the genetic and environmental causes of MS by translational approach integrating molecular genetics and functional studies in rodent models of MS and non- specific CNS damage with large scale studies in clinical MS materials.
Our detailed research plan:
Fine dissection of polymorphic genes regulating rat models of MS and inflammatory neurodegeneration after nerve trauma using advanced intercross lines (AIL), a heterogeneous stock (HS) and recombinant congenic mapping under the assumption that interspecies conserved mechanism may be of relevance for human neuroinflammatory disease.
By comparative genetics, study if the same gene, or genes in the same pathway, are of relevance in human disease.
Functionally dissect these pathways in rodents, and also study potential therapeutic intervention.
Study potential gene-environment interactions in a large ongoing case-control study.
Participate in a large international endeavour on un-biased whole genome scanning of a very large MS case-control cohort (the International Multiple Sclerosis Genetics Consortium, IMSGC). And in follow up studies in the included Swedish material, study relations between genetic variants, gene expression and gene-environment effects.
Identification of polymorphic genes regulating rat models of MS and inflammatory neurodegeneration after nerve trauma
By comparative genetics, is the same gene/pathway relevant in human disease
Study potential therapeutic interventions
Study potential gene-environment interactions in a large ongoing case-control study
Identification of genes regulating MS in patients (the International Multiple Sclerosis Genetics Consortium, IMSGC) and study relations between genetic variants, gene expression and gene-environment effects
Montgomery S, Hiyoshi A, Burkill S, Alfredsson L, Bahmanyar S, Olsson T. Reply to: Concussion may not cause multiple sclerosis. Ann Neurol. 2017 Oct;82(4):652-653. Abstract not available.
Steri M, et al. Overexpression of the Cytokine BAFF and Autoimmunity Risk. N Engl J Med. 2017 Apr 27;376(17):1615-1626.
Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234.
Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017
Häggmark-Månberg A, Zandian A, Forsström B, Khademi M, Lima Bomfim I, Hellström C, Arnheim-Dahlström L, Hallböök T, Darin N, Lundberg IE, Uhlén M, Partinen M, Schwenk JM, Olsson T, Nilsson P. Autoantibody targets in vaccine-associated narcolepsy. Autoimmunity. 2016 Sep;49(6):421-433.
Hedström AK, Alfredsson L, Olsson T. Environmental factors and their interactions with risk genotypes in MS susceptibility. Curr Opin Neurol. 2016 Jun;29(3):293-8.
Ayoglu B, Mitsios N, Kockum I, Khademi M, Zandian A, Sjöberg R, Forsström B, Bredenberg J, Lima Bomfim I, Holmgren E, Grönlund H, Guerreiro-Cacais AO, Abdelmagid N, Uhlén M, Waterboer T, Alfredsson L, Mulder J, Schwenk JM, Olsson T, Nilsson P. Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proc Natl Acad Sci U S A. 2016 Feb
Gustafsson M, Gawel DR, Alfredsson L, Baranzini S, Björkander J, Blomgran R, Hellberg S, Eklund D, Ernerudh J, Kockum I, Konstantinell A, Lahesmaa R, Lentini A, Liljenström HR, Mattson L, Matussek A, Mellergård J, Mendez M, Olsson T, Pujana MA, Rasool O, Serra-Musach J, Stenmarker M, Tripathi S, Viitala M, Wang H, Zhang H, Nestor CE, Benson M. A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases. Sci Transl Med. 2015 Nov 11;7(313):313ra178.
Moutsianas L, et al. Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat Genet. 2015 Oct;47(10):1107-1113.
International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013 Nov;45(11):1353-60.
Ayoglu B, Häggmark A, Khademi M, Olsson T, Uhlén M, Schwenk JM, Nilsson P. Autoantibody profiling in multiple sclerosis using arrays of human protein fragments. Mol Cell Proteomics. 2013 Sep;12(9):2657-72.
Khademi M, Dring AM, Gilthorpe JD, Wuolikainen A, Al Nimer F, Harris RA, Andersson M, Brundin L, Piehl F, Olsson T, Svenningsson A. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers. PLoS One. 2013 May 7;8(5):e63172.
Sandberg-Wollheim M, Olsson T. Cerebrospinal fluid oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald criteria 2010: Yes. Mult Scler. 2013 May;19(6):714-6.