Save Your Maximum Tolerated Dose: How to Diagnose Procedure-Related Spinal Cord Lesions After Lumbar Intrathecal Bolus Administration of Oligonucleotides in Cynomolgus Monkeys
| Autor: | Magdalena Wozniak, Jorge Luft, Peter Korytko, F. Runge, Serge Zander, Lars Mecklenburg, Anne von Keutz, Florian Timo Ludwig, Betina Pajaziti, Annette Romeike, Sven Korte |
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| Rok vydání: | 2020 |
| Předmět: |
010501 environmental sciences
Toxicology Intrathecal 030226 pharmacology & pharmacy 01 natural sciences Spinal Cord Diseases Necrosis 03 medical and health sciences 0302 clinical medicine Lumbar Laboratory Animal Science medicine Animals Injections Spinal 0105 earth and related environmental sciences Oligonucleotide business.industry Monkey Diseases Oligonucleotides Antisense Spinal cord Spinal cord necrosis Macaca fascicularis medicine.anatomical_structure Spinal Cord Anesthesia Maximum tolerated dose Antisense oligonucleotides business |
| Zdroj: | International Journal of Toxicology. 39:510-517 |
| ISSN: | 1092-874X 1091-5818 |
| Popis: | Many potential drugs for treatment of neurodegenerative diseases, particularly antisense oligonucleotides (ASOs), are administered via lumbar intrathecal injection, because these drugs do not cross the blood–brain barrier. Intrathecal injection is a well-established method in cynomolgus monkeys, a species that is used in preclinical safety assessment when other nonrodent species cannot be used. The authors completed intrathecal ASO administration in over 30 preclinical safety studies (>1000 animals and >4500 dose administrations) during which we observed 3 cases of procedure-related spinal cord necrosis (incidence |
| Databáze: | OpenAIRE |
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