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THE NEW APPROACH Introduction For a long period of time it was state of the art to design drugs displaying one defined pharmacological mode of action. These drugs failed in the approach to cure complex diseases! Recently the medical community postulated the need for drugs displaying a mode of action resulting in pleiotropic effects for treatment of complex diseases like CNS injury or neurodegeneration . Introduction The mature central nervous system has limited capacity for selfrenewal and repair after injury or neurodegeneration, therefore therapeutic strategies with effects similar to neurotrophic factors resulting in pleiotropic effects are required. Cerebrolysin acts similar to neurotrophic factors and is therefore an optimal treatment strategy after CNS injury or neurodegeneration. neurogenesis neuroplasticity neuroprotection neuronal survival Cerebrolysin NEUROTROPHIC MECHANISM Cerebrolysin – Indications DEMENTIA STROKE TBI Cerebrolysin – Characterisation Protein powder Starting material Enzymatic hydrolysis Ethanol precipitation Molecular weight cut-off filtration Addition of amino acids Cerebrolysin Concentrate Active Pharmaceutical Ingredient Cerebrolysin – Mode of action Cerebrolysin, a balanced peptide preparation acting like neurotrophic factors. General Pharmacodynamics (PD) Special Pharmacodynamics (PD) Cerebrolysin – General PD The neurotrophic mechanism of Cerebrolysin results in pleiotropic effects: • neuronal survival • neuroprotection • neuroplasticity • neurogenesis Cerebrolysin – General PD Neuronal survival Neurotrophic factors exert survival-promoting and trophic actions on neuronal cells to avoid neuronal atrophy, hypofunction and cell death. Cerebrolysin – General PD Neuroprotection Neurotrophic factors limit neuronal dysfunction and attempt to maintain the highest possible integrity of cellular interactions in the brain under detrimental conditions. Cerebrolysin – General PD Neuroplasticity Neurotrophic factors enable neuroplasticity, a process which allows the brain to adapt by "re-wiring" in response to changes in the environment and which allows the regrowth of damaged neuronal processes. Cerebrolysin – General PD Neurogenesis Neurotrophic factors induce differentiation of progenitor cells to form neurons, which become functionally integrated into the surrounding brain tissue during pre-natal development but also throughout adulthood. Cerebrolysin – General PD Cerebrolysin – General PD Cerebrolysin – Special PD Efficacy of Cerebrolysin has been proven in several invitro and in-vivo experiments with model systems for • Dementia • Stroke • TBI Cerebrolysin – Special PD Model systems for diseases: STROKE DEMENTIA TBI Cerebrolysin – Special PD Findings in Dementia Models: - Cerebrolysin decreases A deposition by regulating APP maturation. - Cerebrolysin acts as a synaptic modulator to promote integrity of neuronal circuits. - Cerebrolysin restores neuronal cytoarchitecture resulting in improved behavioral performance. - Cerebrolysin stimulates neurogenesis in the dendate gyrus, which might provide a basis for neuronal replacement therapy in neurodegenerative diseases. Cerebrolysin – Special PD Findings in Stroke Models: - Cerebrolysin stabilizes cytoskeleton by inhibition of calpain. - Cerebrolysin stimulates neurogenesis to promote integrity of neuronal circuits, a potential mechanisms for self-repair after stroke. - Cerebrolysin decreases infarct volume. - Cerebrolysin limits edema formation. - Cerebrolysin promotes functional recovery. Cerebrolysin – Special PD Findings in TBI Models: - Cerebrolysin prevents apoptosis of lesioned motoneurons. - Cerebrolysin promotes functional recovery. Cerebrolysin – Summary Cerebrolysin, a balanced peptide preparation acting like neurotrophic factors. Cerebrolysin – Summary The neurotrophic mechanism of Cerebrolysin results in pleiotropic effects: • neuronal survival • neuroprotection • neuroplasticity • neurogenesis Cerebrolysin – Summary Efficacy of Cerebrolysin has been proven in several invitro and in-vivo experiments with model systems for • Dementia • Stroke • TBI Cerebrolysin – Conclusion Cerebrolysin is an optimal treatment strategy after CNS injury or neurodegeneration.