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O4‐04–02: Therapeutic effects of gene therapy in the late treatment of prion diseases
Author(s) -
Verdier Jean-Michel,
Toupet Karine,
Compan Valérie,
Crozet Carole,
Mestre-Frances Nadine,
Corbeau Pierre,
Perrier Véronique
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.528
Subject(s) - bovine spongiform encephalopathy , scrapie , disease , fatal familial insomnia , genetic enhancement , prion protein , transmissible spongiform encephalopathy , virology , medicine , in vivo , incubation period , biology , gene , pathology , genetics , incubation , biochemistry
was administered i.m. as single doses once per week. DMTS testing was initiated 60 min after dosing. For two of the 6 doses 0.116 and 1.16 g/kg, data also were obtained 24 hr, 48 hr, and 6 days after drug administration. Results: Clonidine treatment produced a tendency toward improved accuracies after the lowest 3 doses, particularly during long delay trials. However, the effect was not statistically significant. There was a tendency (P 0.09) towards improved accuracy measured during the sessions initiated 24 hr after clonidine administration (with no other pre-test treatment). Because of the trend towards improved accuracy with time after administration we compared the accuracy values obtained 1 hr through 6 days after clonidine administration. For the 0.116 g/kg dose, there was a statistically significant improvement in accuracies associated with long delay trials (P 0.001). The improvement in task accuracies was maintained over the first 3 days of testing. In fact, mean task accuracies measured 24 and 48 hours after clonidine administration were greater than those measured during the 60 min session. Conclusions: Though initial effects on task accuracy obtained from the dose-response study were not statistically significant, for clonidine, the statistics belie the usefulness of the drug. These results not only suggest a role for central noradrenergic mechanisms in memory consolidation, but they point to the need to determine the central pharmacodynamic effects of cognition enhancing compounds when designing clinical treatment regimens. For compounds like clonidine, the efficacy towards cognition enhancement might be underestimated when only a single time point after administration is studied.