Join us on an amazing journey towards next-generation treatments for CNS disorders: Launch of Neuroprotection, a new high-quality journal in translational neuroscience.
Join us on an amazing journey towards next-generation treatments for CNS disorders: Launch of Neuroprotection, a new high-quality journal in translational neuroscience.
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DOI：
10.1002/nep3.8
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发表时间：
2023-09
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重要的是，随着实验研究的内部和外部有效性不断提高，该领域已经从以往的翻译挫折中吸取了教训。与此同时，旨在建立新的治疗方法的临床试验数量也在增加。例如，神经保护目前在中风和创伤性脑损伤的研究和治疗领域正在复兴。卒中早期神经保护范式依赖于急性期和亚急性期全身应用神经保护剂的翻译失败已有报道并进行了详细的分析。虽然以前的临床前研究和结果转化为临床治疗经常受到实验设计缺陷的影响，但该领域的研究质量已大幅提高，今天在许多领域应用的方法严谨性是突出的。1此外，再通疗法的时代现在提供了在需要的时间和地点进行局部神经保护治疗的可能性。2此外，神经保护剂的应用策略也得到了极大的改进。事实上，当代的方法并不主要关注永久性的神经保护，试图通过针对单一的病理机制来挽救更大部分的脑梗塞组织。取而代之的是，他们使用精心设计的方法来保护半影区，以便获得再通的时间，防止再灌注损伤，或者在各自的保护时间窗口针对不同的大脑驻留细胞。3其中许多方法在院前环境中应用是安全的，为更有针对性和更有效的第二代神经保护治疗范例开辟了新的途径。此外，这些新的范例被开发为与包括再通方法在内的既定治疗程序完全兼容。4其他领域也报告了类似的进展。例如，最近的一项多发性硬化症(MS)的双盲随机II期临床试验显示，初步证据表明，间充质干细胞(MSC)移植具有温和但具有临床意义的治疗效果。5骨髓间充质干细胞可通过分泌多种生长因子发挥治疗作用，并具有较强的免疫调节能力，是中枢神经系统再生医学等领域的理想资源。事实上，骨髓间充质干细胞移植伴随着脑脊液中神经细丝L和CXCL-13水平的显著降低，前者表明神经元丢失，后者是一种有效的B细胞趋化物质和MS活动性损害的生物标志物。最近的研究评估了单胺氧化酶B抑制剂雷沙吉兰在帕金森氏病(PD)和淀粉样变性侧索硬化症(ALS)中的神经保护作用。在帕金森病中，雷沙吉兰被用作标准左旋多巴治疗的附加药物，参加了一项随机、双盲、安慰剂对照的II/III期临床试验的日本队列研究。根据运动测量，雷沙吉兰减少了非工作时间，并及时改善了症状
Importantly, the field has learned from previous translational setbacks as the internal and external validity of experimental studies are continuously improving. This is paralleled by an increase in the number of clinical trials aimed at establishing new therapeutic approaches. For instance, neuroprotection is currently seeing a renaissance in the areas of stroke and traumatic brain injury research and treatment. The translational failure of early neuroprotective paradigms for stroke which rely on systemic administration of neuroprotectants during acute and subacute stages has been reported and analyzed in detail. Whereas previous preclinical research and the translation of results obtained therein into clinical treatments were often impaired by shortcomings in experimental design, research quality in the field has improved substantially and methodological rigor applied today is outstanding across many fields. 1 Moreover, the era of recanalization therapies now offers the possibility to apply neuroprotective treatments locally, when and where they are needed. 2 Moreover, the application strategies for neuroprotectants have been greatly refined. Indeed, contemporary approaches do not focus primarily on permanent neuroprotection trying to rescue larger parts of infarcted brain tissue by targeting single pathomechanisms. Instead, they use elaborate approaches to protect the penumbra in order to gain time for recanalization, to prevent reperfusion injury, or to target different brain resident cells in their respective protective time windows. 3 Many of these approaches are safe to be applied in a prehospital setting, opening new ways for more targeted and effective ‘2nd generation’neuroprotective treatment paradigms. Moreover, these new paradigms are developed to be fully compatible with established treatment procedures including recanalization approaches. 4 Similar progress is reported in other fields. For example, a recent double‐blind and randomized phase II clinical trial in multiple sclerosis (MS) revealed preliminary evidence for a modest yet clinically meaningful therapeutic effect of mesenchymal stem cell (MSC) transplantation. 5 MSCs can exert therapeutic effects via the secretion of numerous growth factors and have strong immunomodulatory abilities, making them an ideal resource for central nervous system regenerative medicine and beyond. Indeed, MSC transplantation was accompanied by a marked reduction of cerebrospinal fluid levels of neurofilament L, indicating neuronal loss, and CXCL‐13, a potent B‐cell chemoattractant and biomarker for active lesions in MS.Recent studies have evaluated the therapeutic potential of rasagiline, a monoamine oxidase B inhibitor, regarding its neuroprotective potential in Parkinson's disease (PD) and in amylotrophic lateral sclerosis (ALS). In PD, rasagiline was used as an add‐on to the standard levodopa treatment in a Japanese cohort enrolled into a randomized, double‐blind, placebo‐controlled, Phase II/III clinical trial. Rasagiline reduced OFF‐time and improved symptoms in ON‐time as measured by the Movement