from the 4 MCI Patients on Annovis website:
Proof of Concept Study
?
Annovis conducted an experiment in rats, where it is possible to measure the PK of ANVS401 in plasma, CSF and the brain. Annovis extrapolated human plasma/CSF and rat plasma/CSF/brain levels to calculate human brain levels of ANVS401 and determined they were eight times higher than plasma levels. This is consistent with the data the Company has in mice, where in several studies, ANVS401 brain levels were found to be approximately 6-8 times higher in the brain than in plasma.
ANVS401’s extended presence in the brain is matched by an extended effect, reducing levels of APP, tau and aSYN for the whole 12-hour period tested. The extended effect of ANVS401 in human brains was consistent with the preclinical data in rodent brains.
?:
The persistence of ANVS401 in the CSF and brain and the extended pharmacodynamic effect observed make ANVS401 a good candidate for once a day dosing. Extrapolated brain levels of ANVS401 at 60 mg four times a day are far in excess of levels required to down-regulate APP and aSYN. The doses of ANVS401 needed to lower the levels of neurotoxic proteins are similar for the toxic proteins, suggesting similar dosing in AD-DS, AD and PD. Annovis further compared levels of ANVS401 in the brains of mice that had shown improved memory, learning and colonic motility and calculated that the optimum brain levels are between 150 and 500 nM. Using three different extrapolation/comparisons the Company deduced that a daily dose of 5-6 mg should achieve desired brain levels in humans.
MCI patients were treated for 10 days and CSF and plasma were extracted over 12 hours before the first administration of ANVS401 and after the last administration of ANVS401. The levels of neurotoxic proteins decreased to levels similar to the average found in healthy, normal volunteers.
MCI patients also showed high levels of inflammatory factors and microglia activation factors in their CSF. ANVS-401 significantly lowered the levels of several inflammation factors in their CSF
