TY  - JOUR
A1  - Minnerup, Jens
A1  - Sutherland, Brad A.
A1  - Buchan, Alastair M.
A1  - Kleinschnitz, Christoph
T1  - Neuroprotection for Stroke: Current Status and Future Perspectives
JF  - International Journal of Molecular Science
N2  - Neuroprotection aims to prevent salvageable neurons from dying. Despite showing efficacy in experimental stroke studies, the concept of neuroprotection has failed in clinical trials. Reasons for the translational difficulties include a lack of methodological agreement between preclinical and clinical studies and the heterogeneity of stroke in humans compared to homogeneous strokes in animal models. Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria. However, there are a number of neuroprotective treatments under investigation in clinical trials such as hypothermia and ebselen. Moreover, promising neuroprotective treatments based on a deeper understanding of the complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases and PSD-95 are currently evaluated in preclinical studies. Further concepts to improve translation include the investigation of neuroprotectants in multicenter preclinical Phase III-type studies, improved animal models, and close alignment between clinical trial and preclinical methodologies. Future successful translation will require both new concepts for preclinical testing and innovative approaches based on mechanistic insights into the ischemic cascade.
KW  - free radical scavenger
KW  - ischemic cascade
KW  - acute ischemic stroke
KW  - trial
KW  - focal cerebral-ischemia
KW  - interleukin-1 receptor antagonist
KW  - colony-stimulating factor
KW  - tissue-plasminogen activator
KW  - traumatic brain injury
KW  - placebo-controlled
KW  - alias pilot trial
KW  - damage cool aid
KW  - neuroprotection
KW  - ischemic stroke
KW  - translation
KW  - STAIR
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134730
VL  - 13
IS  - 9
ER  - 
TY  - JOUR
A1  - Kleinschnitz, Christoph
A1  - Niemczyk, Gabriele
A1  - Rehberg-Weber, Karin
A1  - Wernsdörfer, Colin
T1  - Interferon Beta-1a (AVONEX®) as a treatment option for untreated patients with multiple sclerosis (AXIOM): a prospective, observational study
JF  - International Journal of Molecular Sciences
N2  - The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies.
KW  - subcutaneous injection
KW  - therapy
KW  - trial
KW  - relapsing-remitting multiple sclerosis
KW  - injection site reactions;
KW  - efficacy
KW  - quality of life
KW  - disease-modifying therapy
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148487
VL  - 16
ER  - 
TY  - JOUR
A1  - Rovituso, Damiano M.
A1  - Duffy, Catharina E.
A1  - Schroeter, Michael
A1  - Kaiser, Claudia C.
A1  - Kleinschnitz, Christoph
A1  - Bayas, Antonios
A1  - Elsner, Rebecca
A1  - Kuerten, Stefanie
T1  - The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients
JF  - Scientific Reports
N2  - B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-\(\beta\) (IFN-\(\beta\))-treated RRMS patients (n = 23). These data suggest that GA has an effect on brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of brain-reactive B cells is likely to be a suitable tool to identify drug responders.
KW  - cortical pathology
KW  - natural history
KW  - disability
KW  - expression
KW  - antibodies
KW  - disease
KW  - lesions
KW  - trial
KW  - multiple sclerosis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148172
VL  - 5
IS  - 14265
ER  -