Neuroinflammation refers to the inflammation of nervous tissue. Neuroinflammatory diseases include rare forms such as neuromyelitis optica spectrum disorders (NMOSD), MOG-AK-mediated disease (MOG-AK disease), and acute disseminated encephalomyelitis (ADEM). The most common and well-known neuroinflammatory disease is Multiple Sclerosis (MS).
The human body reacts to injuries or pathogens with inflammatory reactions. However, since brain tissue can hardly regenerate and additionally stores information in its neuronal networks, it must be particularly well protected. For this purpose, the central nervous system has its own immune defense system. However, if there is a dysregulation, the resulting inflammations can themselves become a danger to its own nervous tissue.
MS is a chronic inflammatory autoimmune disease of the central nervous system and is considered the most common disabling neurological disease in young people. Generally, it manifests in young adulthood, but in rare cases, it can already occur before the age of 18 years. This early disease manifestation is likely favored by specific environmental factors in combination with a genetic predisposition. In contrast to adults with multiple sclerosis, pediatric patients recover from the symptoms of an MS episode more quickly and usually completely, resulting in slower disease progression. However, due to the early onset of the disease, they are at risk of permanent disability at a younger age.
The Department of Pediatrics and Adolescent Medicine with its German Center of Multiple Sclerosis in Childhood and Adolescence (Deutsches Zentrum für Multiple Sklerose im Kindes- und Jugendalter and https://childrenms.de/ ) is a German leader in the treatment of pediatric multiple sclerosis and maintains the largest registry of children and adolescents with MS from all parts of Germany.
The aim of our research is to understand the early disease manifestation and the course of a pediatric MS disease and to provide a basis for the development of innovative diagnostic and therapeutic procedures.
In this project, the influence of new immunomodulatory agents on the course of pediatric MS will be investigated, also with a view to establishing valid safety profiles for the respective drugs.
Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Gärtner J, Hauser SL, Bar-Or A, Montalban X, Cohen JA, Cross AH, Deiva K, Ganjgahi H, Häring DA, Li B, Pingili R, Ramanathan K, Su W, Willi R, Kieseier B, Kappos L. Mult Scler. 2022 Sep;28(10):1562-1575.
Improving pediatric multiple sclerosis interventional phase III study design: a meta-analysis. Graves JS, Thomas M, Li J, Shah AR, Goodyear A, Lange MR, Schmidli H, Häring DA, Friede T, Gärtner J. Ther Adv Neurol Disord. 2022 May 1;15:17562864211070449. doi: 10.1177/17562864211070449. eCollection 2022.
Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis. Chitnis T, Arnold DL, Banwell B, Brück W, Ghezzi A, Giovannoni G, Greenberg B, Krupp L, Rostásy K, Tardieu M, Waubant E, Wolinsky JS, Bar-Or A, Stites T, Chen Y, Putzki N, Merschhemke M, Gärtner J; PARADIGMS Study Group. N Engl J Med. 2018 Sep 13;379(11):1017-1027.
Pediatric multiple sclerosis: Conventional first-line treatment and general management. Ghezzi A, Amato MP, Makhani N, Shreiner T, Gärtner J, Tenembaum S. Neurology. 2016 Aug 30;87(9 Suppl 2):S97-S102.
Pathogenetic mechanisms of disease development
In this project, pathogenetic mechanisms of disease development will be elucidated to identify those parameters that lead to the unusually early manifestation of MS in childhood and adolescence.
Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis. Bergner CG, Genc N, Hametner S, Franz J, van der Meer F, Mitkovski M, Weber MS, Stoltenburg- Didinger G, Kühl JS, Köhler W, Brück W, Gärtner J, Stadelmann C. Glia. 2021 Oct;69(10):2362-2377.
Association of Obesity With Multiple Sclerosis Risk and Response to First-line Disease Modifying Drugs in Children. Huppke B, Ellenberger D, Hummel H, Stark W, Röbl M, Gärtner J, Huppke P.JAMA Neurol. 2019 Jul 15;76(10):1157-65.
JC virus antibody status in a pediatric multiple sclerosis cohort: prevalence, conversion rate and influence on disease severity. Huppke P, Hummel H, Ellenberger D, Pfeifenbring S, Stark W, Huppke B, Brück W, Gärtner J.Mult Scler. 2015 Apr;21(4):382-7.
This project is about testing potential biomarkers, i.e. quantifiable indicators for MS manifestation and typical progressive demyelination including axonal or neuronal degeneration processes. In the long term, suitable biomarkers will be used for diagnostics, but also for the prediction of individual disease activity and the effect of therapeutics on disease progression.
Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis. Reinert MC, Benkert P, Wuerfel J, Michalak Z, Ruberte E, Barro C, Huppke P, Stark W, Kropshofer H, Tomic D, Leppert D, Kuhle J, Brück W, Gärtner J. Neurol Neuroimmunol Neuroinflamm. 2020 May 13;7(4):e749.