– Can you provide more detailed information about the assumptions and diagnostics used in the statistical analyses to ensure robustness?
– Were lower doses of MK-8189 than 0.3 mg/kg tested, and if so, what were the findings? If not, why were lower doses excluded?
Why was a focused microwave irradiator chosen for euthanasia? Could alternative methods have been used without compromising data integrity?
– In the PET studies, how was the cerebellum validated as a reference region for rhesus monkeys? Were there any discrepancies in uptake across animals?
– Could additional pharmacokinetic comparisons between MK-8189 and other PDE10A inhibitors, including off-target effects, be provided for better context?
– How do you account for variability between animals in determining the threshold for PDE10A EO in behavioral assays?
– The cognitive performance improvement in the ORD task is notable. How does this translate to anticipated effects in humans, given the known interspecies differences?
– Were there any independent validations or oversight mechanisms to address potential biases due to the authors’ affiliation with Merck?
