Immunotherapy of experimental and human stroke with agents approved for multiple sclerosis: a systematic review

Abstract

Background:‘Thromboinflammation’ describes a novel concept in stroke pathophysiology that has opened up the possibility of immunotherapeutic approaches which could become promising strategies for targeted stroke therapies in the future.Methods:We reviewed current evidence for agents approved for multiple sclerosis in preclinical and clinical stroke studies. A systematic review was performed in accordance with the PRISMA statement, searching MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 16 October 2017.Results:The review included 52 of 629 identified studies, consisting of 5 clinical and 47 preclinical trials. Most of the studies showed beneficial effects of the evaluated immunotherapeutic drugs in terms of reduction in morphological lesion size and improvement in functional outcome. Nevertheless, the significance of these findings is limited due to the high degree of heterogeneity.Conclusions:Immunotherapy of stroke might be effective and could become a promising treatment strategy, but larger clinical trials with standardized interventions and outcome measures are needed.

Rapamycin in ischemic stroke: Old drug, new tricks?

“…166 Small clinical trials have shown that fingolimod is well tolerated; however, due to small patient numbers and heterogeneity of the trials, no definitive answer on the efficacy of this therapy can be made at this time. 167 Subcutaneous interleukin-1 receptor antagonist (Anakinra) is another immunomodulatory therapy currently being trialled as an adjunct to thrombolysis in ischemic stroke. 168 This intervention is backed up by many years of animal model evidence, systematic review and meta-analysis 169 and a multicentre randomised pre-clinical trial confirming its efficacy in improving stroke outcome.…”

“…166 Small clinical trials have shown that fingolimod is well tolerated; however, due to small patient numbers and heterogeneity of the trials, no definitive answer on the efficacy of this therapy can be made at this time. 167…”

Filling the gaps on stroke research: Focus on inflammation and immunity

“…The timing of outcome assessment is another factor that contributes to contradictory results between mouse and human studies. While in most clinical studies the neurological outcome is measured in patients up to several months after the stroke (usually 90 days), a vast majority of preclinical studies in mice focus only on the first days after the stroke ( Veltkamp and Gill, 2016 , Dreikorn et al, 2018 ).…”

Thinking Outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke

“…Until 2015, seven animal studies exploring the effects of natalizumab on IS had been published [17]. The majority of them reported a reduction in infarct size with natalizumab administration [32][33][34][35] and an improvement in recovery outcomes [34,35].…”

“…Given the attention inflammation and immune activation has been gathering in the context of IS [14], and the fact that MS treatment modalities targeting the CNS are usually immunosuppressive/immunomodulatory [15,16], research is being conducted on whether substances used in MS can ameliorate IS parameters and recovery. In fact, studies in the respective experimental models have shown that treatment modalities fitted to MS may indeed be beneficial in IS [11,17].…”