NEUROTROPHIC ACTIVITIES AND THERAPEUTIC EXPERIENCE WITH A BRAIN-DERIVED PEPTIDE PREPARATION

In spite that the use of naturally occurring neurotrophic factors like NGF, BDNF, CNTF, GDNF and others for treatment of neurodegenerative d isorders seems promising because of their pharmacological properties, until now no large scale clinical trials have been published. One of t he reasons is that these molecules are unable to penetrate through the blood brain barrier, making invasive application strategies like intr acerebroventricular infusion necessary. Another one is the fact that i n first clinical studies, several undesirable side-effects like hypera lgesia or weight loss have been reported. Major efforts are now put in to development of improved application procedures and in treatment pro tocols for avoiding the known side-effects. Already 7 years ago it has been demonstrated that Cerebrolysin(R), a peptidergic drug, produced from purified brain proteins by standardized enzymatic breakdown, cont aining biologically active peptides, is exerting nerve growth factor l ike activity on neurons from dorsal root ganglia. Still ongoing invest igations are showing growth promoting efficacy of this drug in differe nt neuronal populations from peripheral and central nervous system. Th e current findings are in accordance with several older publications, enabling now a more clear interpretation of these findings. In additio n to the direct neurotrophic effect, the drug also shows clear neuropr otective properties after different types of lesion in vitro and in vi vo, resembling the pharmacological activities of naturally occurring n erve growth factors. Neurotrophic and neuroprotective efficacy has bee n shown with a broad variety of methods in different models and it is remarkable that all biochemical and morphological drug dependent alter ations are resulting in improvements of learning and memory. Because o f these experimental results, clinical trials using cerebrolysin in Al zheimer's patients have been performed, demonstrating a quick improvem ent in the overall state of the patients, particularly enhancing the c ognitive performance. It is remarkable that these effects are long las ting after cessation of the active treatment procedure. Even 6 months after stop of drug application, improvements in AD-patients are detect able. Therefore it is concluded that cerebrolysin is able to induce re pair phenomena, resulting in long term stabilization. In contrast to t he naturally occurring growth factors, tolerability of this drug is ex tremely high, without any reports about serious side-effects in these clinical studies.