Smith D.L. and Woodman B. and Mahal A. and Sathasivam K. and Ghazi-Noori S. and Lowden, Philip and Bates G.P. and Hockly E. (2003) Minocycline and doxycycline are not beneficial in a model of Huntington's disease. Annals of Neurology 54 (2), pp. 186-196. ISSN 0364-5134.
Abstract
Huntington's Disease (HD) is an inherited neurological disorder causing movement impairment, personality changes, dementia, and premature death, for which there is currently no effective therapy. The modified tetracycline antibiotic, minocycline, has been reported to ameliorate the disease phenotype in the R6/2 mouse model of HD. Because the tetracyclines have also been reported to inhibit aggregation in other amyloid disorders, we have investigated their ability to inhibit huntingtin aggregation and further explored their efficacy in preclinical mouse trials. We show that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30μM. However, despite achieving tissue levels approaching this concentration by oral treatment of R6/2 mice with minocycline, we observed no clear difference in their behavioral abnormalities, or in aggregate load postmortem. In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline. Ann Neurol 2003
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Sarah Hall |
| Date Deposited: | 07 May 2019 15:46 |
| Last Modified: | 02 Aug 2023 17:51 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/27432 |
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