Name:	Cerebrolysin
Therapeutic Applications:	Improvement of cognitive and behavioral functions and in activities of daily living.
Therapy Types:	pharmacological: injectable peptide solution
Mechanisms:	Neuroprotection, neurotrophic agent, promotes neurogenesis, may decrease rate of apoptosis.
FDA Phase:	Approved outside U.S.
Primary Medical Role:	Treatment of Alzheimer's Disease
Role in Alzheimer's Disease:	Cerebrolysin is a peptide-based drug product supporting the survival, stability, and function of neurons. Cerebrolysin decreases amyloid production, promotes synaptic repair, and improves cognitive and behavioral performance.
Pharmacological Role:	It is 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. Neurotrophic and neuroprotective agent. It improves behavioral performance by affecting synaptic transmission in the hippocampus.
Contraindications:	Hypersensitivity to one of the components of the drug, epilepsy, severe renal impairment.
Side Effects:	Cerebrolysin is generally well tolerated. If injected too quickly it may cause a moderate heat sensation. In extremely rare cases hypersensitivity reactions manifest themselves as chills, headaches, or slight increases in body temperature of the patient. In no case to date has the undesirable effect persisted or proved threatening to the patient’s health.
Evidence pro its efficacy:	Efficacy was demonstrated in randomized controlled clinical trials on different levels of clinical ailment by using standardized and validated assessment scales. Significant improvement of the patients was demonstrated in clinical global impression (CGI, CIBIC; 0.25–0.45 points), cognitive performance (MMSE, SKT, Trail-Making test, ADAS-cog [2–4 points]) and on the level of activities of daily living (NAI, DAD). Cerebrolysin has a fast onset of action (1 month) and beneficial effects are maintained up to 3 months after cessation of treatment.
Companies:	Ebewe Pharmaceutical
Notes:	Approved in 44 countries worldwide, for stroke, dementia, and traumatic brain injury. Cerebrolysin is currently in Phase 3 in multiple countries in Europe.

References

Rockenstein E, Torrance M, Mante M, Adame A, Paulino A, Rose JB, Crews L, Moessler H, Masliah E. Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease. J Neurosci Res. 2006 May 15;83 (7):1252-61. Abstract

Alvarez XA, Cacabelos R, Laredo M, Couceiro V, Sampedro C, Varela M, Corzo L, Fernandez-Novoa L, Vargas M, Aleixandre M, Linares C, Granizo E, Muresanu D, Moessler H. A 24- week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease. Eur J Neurol. 2006 Jan 1;13(1):43-54. Abstract

Rockenstein E, Adame A, Mante M, Larrea G, Crews L, Windisch M, Moessler H, Masliah E. Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer's disease with the neurotrophic compound cerebrolysin. J Neural Transm. 2005 Feb 1;112(2):269-82. Abstract

Rockenstein E, Adame A, Mante M, Moessler H, Windisch M, Masliah E. The neuroprotective effects of Cerebrolysin trade mark in a transgenic model of Alzheimer's disease are associated with improved behavioral performance. J Neural Transm. 2003 Nov ;110(11):1313-27. Abstract

Tatebayashi Y, Lee MH, Li L, Iqbal K, Grundke-Iqbal I. The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease. Acta Neuropathol (Berl). 2003 Mar ;105 (3):225-32. Abstract

Panisset M, Gauthier S, Moessler H, Windisch M. Cerebrolysin in Alzheimer's disease: a randomized, double- blind, placebo-controlled trial with a neurotrophic agent. J Neural Transm. 2002 Jul ;109(7-8):1089-104. Abstract

Muresanu DF, Rainer M, Moessler H. Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin. J Neural Transm Suppl. 2002 ;:277-85. Abstract

Ruether E, Alvarez XA, Rainer M, Moessler H. Sustained improvement of cognition and global function in patients with moderately severe Alzheimer's disease: a double- blind, placebo-controlled study with the neurotrophic agent Cerebrolysin. J Neural Transm Suppl. 2002 ;:265-75. Abstract

Ruether E, Husmann R, Kinzler E, Diabl E, Klingler D, Spatt J, Ritter R, Schmidt R, Taneri Z, Winterer W, Koper D, Kasper S, Rainer M, Moessler H. A 28-week, double- blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease. Int Clin Psychopharmacol. 2001 Sep ;16(5):253-63. Abstract

Bae CY, Cho CY, Cho K, Hoon Oh B, Choi KG, Lee HS, Jung SP, Kim DH, Lee S, Choi GD, Cho H, Lee H. A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease. J Am Geriatr Soc. 2000 Dec 1;48 (12):1566-71. Abstract

Molloy DW, Standish TI. Clinical experience with Cerebrolysin. J Neural Transm Suppl. 2000;59:293-300 Abstract

Ruther E, Ritter R, Apecechea M, Freytag S, Gmeinbauer R, Windisch M. Sustained improvements in patients with dementia of Alzheimer's type (DAT) 6 months after termination of Cerebrolysin therapy. J Neural Transm. 2000;107(7):815-29. Abstract

Veinbergs I, Mante M, Mallory M, Masliah E. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J Neural Transm Suppl. 2000;59:273-80. Abstract

Lombardi VR, Windisch M, Garcia M, Cacabelos R. Effects of Cerebrolysin on in vitro primary microglial and astrocyte rat cell cultures. Methods Find Exp Clin Pharmacol. 1999 Jun;21(5):331-8. Abstract

Masliah E, Armasolo F, Veinbergs I, Mallory M, Samuel W. Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. Pharmacol Biochem Behav. 1999 Feb;62(2):239-45. Abstract

Funke M, Fiehler J, Mewes I, Eiselt M, Rother I, Windisch M. Dose-dependent effects of Cerebrolysin on EEG and short- term memory of healthy volunteers during control and hyperventilation induced cerebral ischemia. J Neural Transm Suppl. 1998;53:385-98. Abstract

Schwab M, Schaller R, Bauer R, Zwiener U. Morphofunctional effects of moderate forebrain ischemia combined with short- term hypoxia in rats--protective effects of Cerebrolysin. Exp Toxicol Pathol. 1997 Feb;49(1-2):29-37. Abstract

Rainer M, Brunnbauer M, Dunky A, Ender F, Goldsteiner H, Holl O, Kotlan P, Paulitsch G, Reiner C, Stossl J, Zachhuber C, Mossler H. Therapeutic results with Cerebrolysin in the treatment of dementia. Wien Med Wochenschr. 1997;147(18):426-31. Abstract

Francis-Turner L, Valouskova V. Nerve growth factor and nootropic drug Cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbria-fornix transection: short-term study. Neurosci Lett. 1996 Jan 5;202(3):193-6. Abstract