Signatures of immune reprogramming in anti-CD52 therapy of MS: markers for risk stratification and treatment response
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(2019) 1:40
Neurological Research and Practice
CLINICAL TRIAL PROTOCOL
Open Access
Signatures of immune reprogramming in anti-CD52 therapy of MS: markers for risk stratification and treatment response Laura Bierhansl* , Tobias Ruck, Steffen Pfeuffer, Catharina C. Gross, Heinz Wiendl and Sven G. Meuth
Abstract Background: Multiple sclerosis is one of the most prevalent neurological diseases in young adults affecting over 2 million people worldwide. Alemtuzumab is a highly effective therapy in relapsing remitting MS. Alemtuzumab is a monoclonal CD52 antibody that proved its efficacy against an active comparator (interferon [IFN]-β1a) in a phase II trial and two phase III trials regarding clinical and MRI outcomes. Nevertheless, the exact mode of action is still unknown. Alemtuzumab is commonly associated with secondary autoimmune disorders significantly affecting the risk-benefit ratio. Therefore, new biomarkers predicting treatment response and adverse events are urgently needed. This study aims to further elucidate the mechanism of action of the neuroprotective potential of alemtuzumab in relapsing-remitting multiple sclerosis (RRMS). Methods/Design: This is a 3-year multicentre, explorative study including overall 150 patients comprising three different groups: (i) de novo patients prior and after alemtuzumab treatment initiation, (ii) patients under alemtuzumab treatment and (iii) patients requiring more than two alemtuzumab infusions. Peripheral blood and serum samples will be collected semi-annually for several in vitro/ex vivo assays to detect and characterize immune cells including their functional activity. Furthermore, data of MRI scans and disease-related impairment (using EDSS and MSFC), as well as the number and time of relapses, will be assessed. The clinical study is registered at clinicaltrials.gov (NCT04082260). Perspective: Our study will provide deep insights into the underlying immunological changes in a longitudinal analysis of alemtuzumab treated RRMS patients. By combining clinical, radiological and functional immunephenotype data, we will be able to identify biomarkers and/or immune signatures predicting treatment response and adverse events. Thereby, the understanding of the mechanisms of action of alemtuzumab will improve its efficacy and safety for present and future patients. Keywords: Relapse-remitting multiple sclerosis, Alemtuzumab, CD52, Biomarker, mechanism of action, secondary autoimmune disease, Disease-modifying therapy, risk stratification
Background Multiple sclerosis affects over 2 million people worldwide and most commonly young adults usually above the second and below the fourth decade of life [1]. Pathological hallmarks of MS are inflammation, demyelination, oligodendrocyte death, axonal damage and neurodegeneration [2]. Therefore, many therapies have been established to modify the adaptive immune system to * Correspondence: [email protected] Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-C
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