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 neuro-degenerative 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 intracere-broventricular 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.
KeywordsNerve Growth Factor Dorsal Root Ganglion Brain Derive Neurotrophic Factor Spatial Navigation Neurotrophic Activity
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- Albrecht E, Hingel S, Crailsheim K, Windisch M (1993) The effects of cerebrolysin on survival and sprouting of neurons from cerebral hemispheres and from the brainstem of chick embryos in vitro. Adv Biosci 87: 341–442Google Scholar
- Anand R, Gharabawi G (1996) Clinical development of ExelonTM (ENA-713): the Adena programme. J Drug Dev Clin Pract 8: 117–122Google Scholar
- Boissiere F, Hunot S, Faucheeux B, Mouatt-Prigent A, Agid Y, Hirsch EC (1997) Trk neurotrophin receptors in cholinergic neurons of patients with Alzheimer’s disease. Dementia 8: 1–8Google Scholar
- Cummings J, Bieber F, Mas J, Orazem J, Gulanski B (1997) Metrifonate in Alzheimer’s disease: results of a dose-finding study. In: Iqbal K, Winblad B, Nishimura T, Takeda M, Wisniewski HM (eds) Alzheimer’s disease: biology, diagnosis and therapeutics. Wiley, New York, pp 659–669Google Scholar
- Gschanes A, Windisch M (1997) The influence of brain-derived peptides on spatial navigation of young and adult rats. Soc Neurosci Abstr 23: 1842Google Scholar
- Hampson DR, Windisch M, Baskys A (1997) Increased binding of BDNF to trkB induced by the antidementia drug cerebrolysin. Soc Neurosci Abstr 23: 1896Google Scholar
- Hefti F (1994) Growth factors and neurodegeneration. In: Calne D (ed) Neuro-degenerative diseases. Saunders, Philadelphia, pp 177–194Google Scholar
- Hutter-Paier B, Eggenreich U, Windisch M (1996) Effects of two protein-free peptide derivatives on passive avoidance behaviour of 24-month-old rats. Arzneimit-telforschung/Drug Res 46/1: 237–241Google Scholar
- Hutter-Paier B, Frühwirth M, Windisch M (1996b) Ischemia induced loss of map2 is prevented by cerebrolysin and THA. Mol Biol Cell 7: 1278Google Scholar
- Lin JH, Hu GY, Tang XC (1997) Comparison between huperzine A, tacrine, and E2020 on cholinergic transmission at mouse neuromuscular junction in vitro. Chung Kuo Yao Li Hsueh Pao 18/1: 6–10Google Scholar
- Masliah E, Armasola F, Veinbergs I, Mallory M, Samuel W (1997) Neurotrophic and neuroprotective effects of cerebrolysin in experimental models of neuro-degeneration. Internal Research ReportGoogle Scholar
- Satou T, Imano M, Akai F, Hashimoto S, Itoh T, Fujimoto M (1993) Morphological observation of effects of cerebrolysin on cultured neural cells. Adv Biosci 87: 195–196Google Scholar
- Satou T, Itoh T, Fujimoto M, Hashimoto S (1994) Neurotrophic-like effects of FPF-1070 on cultured neurons from chick embryonic dorsal root ganglia. Jpn Pharmacol Ther 22/4: 205–212Google Scholar
- Shimazu S, Iwamoto N, Itoh T, Akasako A, Seki H, Jujimoto M (1991) Neurotrophic activity of cerebrolysin. Second International Springfield Symposium on Advantage in Alzheimer Therapy, Springfield, USA, p 51Google Scholar
- Siegfried K (1995) The efficacy of cholinergic drugs in patients with Alzheimer’s disease — focus on the aminoacridines. Humanpsychopharmacology 10: 89–96Google Scholar
- Suchanek-Fröhlich H, Wunderlich E (1987) Randomized, plazebo-controlled, double-blind study with an amino-acid-peptid extract. Prakt Arzt 1: 1027–1034Google Scholar