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

Abstract

In pre-clinical studies, Bryostatin, MW (molecular weight) 904, has demonstrated synaptogenic, anti-apoptotic, anti-amyloid, and anti-tau tangle efficacies. To identify AD patients who show significant cognitive benefit versus placebo when treated in a trial with chronic Bryostatin dosing. 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. 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 by Week #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. The Bryostatin-treated MMSE 10-14 patients showed no significant cognitive decline throughout the 10-month trial, versus placebo patients' decline of -12.8 SIB points.