دورية أكاديمية
Awake intracerebroventricular delivery and safety assessment of oligonucleotides in a large animal model
| العنوان: | Awake intracerebroventricular delivery and safety assessment of oligonucleotides in a large animal model |
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| المؤلفون: | Hector Ribeiro Benatti, Rachel D. Prestigiacomo, Toloo Taghian, Rachael Miller, Robert King, Matthew J. Gounis, Ugur Celik, Stephanie Bertrand, Susan Tuominen, Lindsey Bierfeldt, Elizabeth Parsley, Jillian Gallagher, Erin F. Hall, Abigail W. McElroy, Miguel Sena-Esteves, Anastasia Khvorova, Neil Aronin, Heather L. Gray-Edwards |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 31, Iss , Pp 101122- (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | oligonucleotide safety assessment, large animal model, CNS drug administration, CSF drug delivery, i.c.v. injection, Ommaya reservoir, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S2329050123001614Test; https://doaj.org/toc/2329-0501Test |
| DOI: | 10.1016/j.omtm.2023.101122 |
| الوصول الحر: | https://doaj.org/article/47746a402a8d49c9b29336720b82daaeTest |
| رقم الانضمام: | edsdoj.47746a402a8d49c9b29336720b82daae |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 |
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| DOI: | 10.1016/j.omtm.2023.101122 |