{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:33:01Z","timestamp":1791419581162,"version":"4.3.3"},"reference-count":60,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:00:00Z","timestamp":1493683200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2017,5,11]]},"abstract":"<jats:p>\n                    Bryostatin 1, a potent activator of protein kinase C epsilon (PKC \u025b), has been shown to reverse synaptic loss and facilitate synaptic maturation in animal models of Alzheimer\u2019s disease (AD), Fragile X, stroke, and other neurological disorders. In a single-dose (25 \u03bcg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ) randomized double-blind Phase IIa clinical trial, bryostatin levels reached a maximum at 1-2\u200ah after the start of infusion. In close parallel with peak blood levels of bryostatin, an increase of PBMC PKC \u025b was measured ( p\u200a=\u200a0.0185) within 1\u200ah from the onset of infusion. Of 9 patients with a clinical diagnosis of AD, of which 6 received drug and 3 received vehicle within a double-blind protocol, bryostatin increased the Mini-Mental State Examination (MMSE) score by +1.83\u00b10.70 unit at 3\u200ah versus \u20131.00\u00b11.53 unit for placebo. Bryostatin was well tolerated in these AD patients and no drug-related adverse events were reported. The 25 \u03bcg\/m\n                    <jats:sup>2<\/jats:sup>\n                    administered dose was based on prior clinical experience with three Expanded Access advanced AD patients treated with bryostatin, in which return of major functions such as swallowing, vocalization, and word recognition were noted. In one Expanded Access patient trial, elevated PKC \u025b levels closely tracked cognitive benefits in the first 24 weeks as measured by MMSE and ADCS-ADL psychometrics. Pre-clinical mouse studies showed effective activation of PKC \u025b and increased levels of BDNF and PSD-95. Together, these Phase IIa, Expanded Access, and pre-clinical results provide initial encouragement for bryostatin 1 as a potential treatment for AD.\n                  <\/jats:p>","DOI":"10.3233\/jad-170161","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T11:59:20Z","timestamp":1493985560000},"page":"521-535","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":115,"title":["Bryostatin Effects on Cognitive Function and PKC\u025b in Alzheimer\u2019s Disease Phase IIa and Expanded Access Trials"],"prefix":"10.1177","volume":"58","author":[{"given":"Thomas J.","family":"Nelson","sequence":"first","affiliation":[{"name":"Blanchette Rockefeller Neurosciences Institute, Morgantown, WV, USA"},{"name":"West Virginia University, Morgantown, WV, 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