In order to determine whether daily gel use was required for efficacy, we tested the activity of the two most protective gels, MIV-150/zinc acetate and zinc acetate alone, when applied every other day for 4 weeks, followed by virus challenge 24 h after the last gel.
Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice.
They concluded that telcagepant is unlikely to block CGRP action in the CNS and that CNS penetration is unlikely to be required for efficacy.
Preclinical studies demonstrate that, depending on the timing of the intervention, antibody effector functions mediated by the Fc region may not be required for efficacy [ 3, 29- 31].
Emerging data suggest that differential inhibition of select HDAC enzymes is required for efficacy among different tissues, and much emphasis has been placed on developing selective HDAC inhibitors to improve efficacy.
However, because beneficial effects of β-blockade therapy might require chronic-dosing-induced remodeling of cardiac channels, chronic treatment with propranolol might be required for efficacy in RTT mice.
Molecules may have distinct functions in different cellular contexts, therefore rigorous target validation is critical [ 260, 261]; if a signalling protein has a scaffold function, disruption of protein-protein interactions may be required for efficacy.
However, acute treatment with the β-antagonist propranolol has been previously shown ineffective in preventing these cardiac problems in RTT mice, suggesting that chronic treatment might be required for efficacy.
These and other clinical failures summarized elsewhere,, underscore the complex nature of S. aureus pathogenicity and suggest that a multiantigen vaccine designed to address major bacterial pathogenesis mechanisms will be required for efficacy.
