Advanced Alzheimer's Disease Patients Show Safe, Significant, and Persistent Benefit in 6-Month Bryostatin Trial

Background: In pre-clinical studies, Bryostatin, MW(molecular weight) 904, has demonstrated synaptogenic, anti-apoptotic, anti-amyloid, and anti-tau tangle efficacies. Objective: To identify AD patients who show significant cognitive benefit versus placebo when treated in a trial with chronic Bryostatin dosing. Methods: In this 6-month 122 AD patient Bryostatin trial, there were two cohorts: the Moderate Cohort (MMSE, Mini-Mental Status Exam: 15-18) and the Moderately Severe Cohort (MMSE 10-14) as pre-specified secondary endpoints. Patient randomization was stratified by baseline SIB to insure balance in baseline cognitive ability between treatment arms. Results: With no safety events noted by the data safety and monitoring board, the Moderately Severe (MMSE 10-14) Bryostatin-treated patients were significantly improved above the placebo patients for Weeks #13 through Week #42. After two cycles of 7 x i.v. Bryostatin doses over a 26-week period, the 10-14 Cohort Severe Impairment Battery (SIB), measured every 2 weeks, showed significant benefit using a Mixed Model Repeated Measures model (MMRM, 2-tailed, p < 0.05) for Weeks #13 through #42, even 16 weeks after dosing completion by Week #26. Placebo 10-14 patients showed no benefit, declining to negative 12.8 points byWeek #42. Trend analyses confirmed the MMRM data for this Cohort, with a significant downward slope (equivalent to Cognitive Decline) for the placebo group, p < 0.001, 2-tailed, but no significant decline for the Bryostatin-treated group (p = 0.409, NS), treatment versus placebo p < 0.007. The Moderate Cohort patients showed no significant benefit. Conclusions: The Bryostatin-treatedMMSE10-14 patients showed no significant cognitive decline throughout the 10-month trial, versus placebo patients' decline of -12.8 SIB points.