Windisch M, Gschanes A, Hutter-Paier B
Institute of Experimental Pharmacology, Research Initiative Ebewe, Graz, Austria.
J Neural Transm Suppl. 1998;53:289-98. doi: 10.1007/978-3-7091-6467-9_25.
In spite that the use of naturally occurring neurotrophic factors like NGF, BDNF, CNTF, GDNF and others for treatment of neurodegenerative disorders seems promising because of their pharmacological properties, until now no large scale clinical trials have been published. One of the reasons is that these molecules are unable to penetrate through the blood brain barrier, making invasive application strategies like intracerebroventricular infusion necessary. Another one is the fact that in first clinical studies, several undesirable side-effects like hyperalgesia or weight loss have been reported. Major efforts are now put into development of improved application procedures and in treatment protocols for avoiding the known side-effects. Already 7 years ago it has been demonstrated that Cerebrolysin, a peptidergic drug, produced from purified brain proteins by standardized enzymatic breakdown, containing biologically active peptides, is exerting nerve growth factor like activity on neurons from dorsal root ganglia. Still ongoing investigations are showing growth promoting efficacy of this drug in different neuronal populations from peripheral and central nervous system. The current findings are in accordance with several older publications, enabling now a more clear interpretation of these findings. In addition to the direct neurotrophic effect, the drug also shows clear neuroprotective properties after different types of lesion in vitro and in vivo, resembling the pharmacological activities of naturally occurring nerve growth factors. Neurotrophic and neuroprotective efficacy has been shown with a broad variety of methods in different models and it is remarkable that all biochemical and morphological drug dependent alterations are resulting in improvements of learning and memory. Because of these experimental results, clinical trials using cerebrolysin in Alzheimer's patients have been performed, demonstrating a quick improvement in the overall state of the patients, particularly enhancing the cognitive performance. It is remarkable that these effects are long lasting after cessation of the active treatment procedure. Even 6 months after stop of drug application improvements in AD-patients are detectable. Therefore it is concluded that cerebrolysin is able to induce repair phenomena, resulting in long term stabilization. In contrast to the naturally occurring growth factors, tolerability of this drug is extremely high, without any reports about serious side-effects in these clinical studies.
尽管使用天然存在的神经营养因子（如神经生长因子、脑源性神经营养因子、睫状神经营养因子、胶质细胞源性神经营养因子等）治疗神经退行性疾病因其药理特性似乎很有前景，但到目前为止，尚未发表大规模的临床试验。原因之一是这些分子无法穿透血脑屏障，使得诸如脑室内输注等侵入性应用策略成为必要。另一个原因是，在最初的临床研究中，已经报告了一些不良副作用，如痛觉过敏或体重减轻。目前主要致力于开发改进的应用程序和治疗方案，以避免已知的副作用。早在7年前就已证明，脑蛋白水解物是一种肽能药物，由纯化的脑蛋白经标准化酶解产生，含有生物活性肽，对背根神经节的神经元具有类似神经生长因子的活性。正在进行的研究表明，这种药物在周围和中枢神经系统的不同神经元群体中具有促进生长的功效。目前的研究结果与一些较早的出版物一致，现在能够对这些发现进行更清晰的解释。除了直接的神经营养作用外，该药物在体外和体内不同类型的损伤后也表现出明显的神经保护特性，类似于天然存在的神经生长因子的药理活性。在不同模型中，通过多种方法已证明了其神经营养和神经保护功效，值得注意的是，所有与药物相关的生化和形态学改变都导致学习和记忆的改善。基于这些实验结果，已对阿尔茨海默病患者进行了使用脑蛋白水解物的临床试验，结果表明患者的整体状态迅速改善，尤其是认知能力得到增强。值得注意的是，在停止积极治疗程序后，这些效果仍然持久。即使在停药后6个月，仍可检测到阿尔茨海默病患者的改善情况。因此得出结论，脑蛋白水解物能够诱导修复现象，从而实现长期稳定。与天然存在的生长因子相比，这种药物的耐受性极高，在这些临床研究中没有关于严重副作用的任何报告。
