RVX-208 Exploratory Study Illustrates Early Potential for Alzheimer's Disease
News Nov 11, 2008
Resverlogix Corp. has announced that treatment with its lead drug RVX-208, a first in class ApoA-I/Prebeta-HDL elevating drug, in a post-hoc analysis from the Phase 1a clinical trial found that treatment with RVX-208 resulted in a positive trend on an important marker of cognitive function and Alzheimer's disease, Amyloid-beta40 is an important constituent of amyloid plaques in the brains of Alzheimer's patients.
The analysis of the plasma markers for Alzheimer's disease was performed by Dr. D. Larry Sparks, Senior Scientist and Head of the Roberts Laboratory for Neurodegenerative Disease Research at Sun Health Research Institute in Sun City, Arizona.
The Phase 1a trial, a double-blind, dose-escalation, placebo-controlled trial enrolled 24 subjects in three separate dosing cohorts for a period of one week: 6 received placebo, and 6 received 2mg/kg per day, 6 received 3mg/kg per day and 6 received 8 mg/kg per day of RVX-208.
Plasma levels of A-beta (A-beta40) were measured on day 1 and 7. A 12-14 percent increase in plasma A-beta40 levels was observed at the highest dose of RVX-208 after 7 days of dosing. Based on the study hypothesis these results trended towards significance versus placebo, even with the minimal number of study subjects.
Emerging evidence from large epidemiology studies such as the Harvard Women's Study, the Honolulu-Asia Aging Study and the Whitehall II study continue to build support for the relationship between poor HDL and ApoA-I levels and decreased cognitive function and Alzheimer's disease.
Dr. Sparks's investigation of elective statin use and fractionated cholesterol levels in the ADAPT cohort has identified a significant relationship between elevated HDL levels and better performance on the Mini Mental State Examination (MMSE), and a significant inverse relationship between increased total and LDL cholesterol and learning and memory.
Elevated cholesterol levels are thought to increase the production and accumulation of the putative AD neurotoxin, amyloid-beta (A-beta). The A-beta peptide is produced by aberrant cleavage of a larger precursor protein resulting in two lengths, either 42 or 40 amino acids long.
"Stemming from RVX-208's effects on ApoA-I, Prebeta-HDL production and the facilitation of reverse cholesterol transport, we hypothesized that RVX-208 might increase circulating A-beta40 levels through its effects on functional HDL, which can act as a sponge to draw A-beta40 from the brain to the circulation, for enhanced clearance from the body," stated Dr. Sparks.
"Although it was a pilot study, with minimal subjects, we were pleased to find a positive signal and look forward to performing further research on RVX-208 in this critical area of unmet medical need," Dr. Sparks added.
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