[843] Multiple Sclerosis, Neuroimmunology, Experimental Autoimmune Encephalitis

Research areas: neuroimmunology, experimental autoimmune encephalitis (EAE), multiple sclerosis (MS), biomarkers in neurological diseases.

Our group is focused in the field of neuroimmunology, including multiple sclerosis (MS) and its animal model the experimental autoimmune encephalitis (EAE).

In EAE, we investigate several transgenic mice associated with modification of the inflammatory profile, in order to evaluate their effect on disease course. One of our major interests is to study the role hepatocyte growth factor (HGF). We recently showed that HGF, a well known neuroprotective factor, inhibits central nervous system (CNS) autoimmunity and prevent EAE development. By the mean of transgenic mice overexpressing HGF in the CNS, we demonstrated that this effect is mediated through an induction of tolerogenic dendritic cells and Foxp3+ regulatory T cells as well as an induction of a strong T-helper cell type 2 cytokine bias. Our results suggest that, by combining both potentially neuroprotective and immunomodulatory effects, HGF is a promising candidate for the development of new treatments for immune-mediated demyelinating diseases associated with neurodegeneration such as MS.

In MS, we investigate the mechanism of action (MoA) of disease-modifying therapy such as Glatiramer acetate (GA), Interferon beta and Cladribine. We recently showed that GA had an effect on naïve T cells and triggers monocytes toward a less inflammatory pattern through the IL-1/IL-1Ra system. We also investigate the potential neuroprotective effect of IFN-beta via the measurement of neuroprotective factors secreted by inflammatory cells. In addition, we recently initiated a prospective study on the MoA of Cladribine in MS patients, a new oral therapy for MS. Finally, we have a particular interest in defining and validating new biomarkers that may be useful for MS and other inflammatory diseases of the CNS. We are currently investigating IL-6 and NF-L in the cerebrospinal fluid of MS patients and also develop new proteomic approaches to examine the CSF of patients with demyelinating diseases of the CNS.



Scientific articles

  • A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients - A twelve month follow-up. Derfuss T, Curtin F, Guebelin C, Bridel C, Rasenack M, Matthey A, Du Pasquier R, Schluep M, Desmeules J, Lang AB, Perron H, Faucard R, Porchet H, Hartung HP, Kappos L, Lalive PH. J Neuroimmunol. 2015 Aug 15;285:68-70. doi: 10.1016/j.jneuroim.2015.05.019. Epub 2015 May 20. PMID: 26198921
  • Cerebrospinal fluid angiotensin-converting enzyme for diagnosis of neurosarcoidosis. Bridel C, Courvoisier DS, Vuilleumier N, Lalive PH. J Neuroimmunol. 2015 Aug 15;285:1-3. doi: 10.1016/j.jneuroim.2015.05.020. Epub 2015 May 21.PMID: 26198911
  • Hematologic modifications in natalizumab-treated multiple sclerosis patients: An 18-month longitudinal study. Bridel C, Beauverd Y, Samii K, Lalive PH. Neurol Neuroimmunol Neuroinflamm. 2015 Jun 18;2(4):e123. doi: 10.1212/NXI.0000000000000123. eCollection 2015 Aug
  • Successful long-term ambulatory norepinephrine infusions in a patient with pure autonomic failure. Zekeridou A, Michel P, Medlin F, Hayoz D, Lalive PH, Kuntzer T. Clin Auton Res. 2015 Jul 3. [Epub ahead of print] PMID: 26138858


Scientific articles

  • Hepatocyte growth factor: A regulator of inflammation and autoimmunity. Molnarfi N, Benkhoucha M, Funakoshi H, Nakamura T, Lalive PH. Autoimmun Rev. 2015 Apr;14(4):293-303. doi: 10.1016/j.autrev.2014.11.013. Epub 2014 Dec 1. Review. PMID: 25476732
  •  A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients. Derfuss T, Curtin F, Guebelin C, Bridel C, Rasenack M, Matthey A, Du Pasquier R, Schluep M, Desmeules J, Lang AB, Perron H, Faucard R, Porchet H, Hartung HP, Kappos L, Lalive PH. Mult Scler. 2015 Jun;21(7):885-93. doi: 10.1177/1352458514554052. Epub 2014 Nov 12. PMID: 25392325
  •  Transient gadolinium leakage in natalizumab-treated multiple sclerosis.Haller S, Barkhof F, Wattjes MP, Lalive PH. J Neurol Neurosurg Psychiatry. 2015 Apr;86(4):475-6. doi: 10.1136/jnnp-2014-309069. Epub 2014 Sep 22. No abstract available. PMID: 25246642
  •  Minimal supportive treatment in natalizumab-related PML in a MS patient. Lalive PH, Bridel C, Ferfoglia RI, Kaiser L, Du Pasquier R, Barkhof F, Haller S. J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):354-5. doi: 10.1136/jnnp-2014-308154. Epub 2014 Jun 23. No abstract available. PMID: 24957322