# Long-term therapeutic effects of synthetic bryostatin-1 in advanced AD without memantine

> **NIH NIH R44** · SYNAPTOGENIX, INC. · 2021 · $1,732,392

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Miao-Kun Sun
Project Summary/Abstract
The importance of memory impairment and dementias, including Alzheimer’s disease (AD), as a global priority
has been well recognized. Many compounds that target AD pathologies have been developed preclinically but
have failed in clinical trials, mostly for the lack of therapeutic efficacies.
 Neurotrope Bioscience Inc. is developing bryostatin-1, a relatively selective protein kinase Cε activator, for
the treatment of AD (IND 71,276). Bryostatin-1 has a combination of some unique pharmacological profiles,
including enhancing activation of the brain-derived neurotrophic factor (BDNF) signaling pathways, pro-synaptic
remodeling, pro-synaptogenesis, pro-synaptic maturation, anti-apoptosis, anti-Aβ oligomers, anti-
hyperphosphorylated tau, and anti-inflammatory. Importantly, at appropriate doses, it has been found well
tolerated in clinical trials and to produce a period of therapeutic efficacy for the treatment of the advanced AD
patients in the absence of memantine. It is not clear, however, whether the therapeutic benefit would last, a
profile highly desirable for AD, which lasts years and even decades. The objective of this proposal is to directly
test the long-term therapeutic benefit of the chronic bryostatin-1 (synthetic) treatment for the advanced AD
patients. The proposed study will establish whether a 12-week treatment with synthetic bryostatin-1, through
restoring synaptic functions and enhancing synaptic capacity in supporting cognitive challenges in addition
to actions of anti-AD pathologies, will effectively produce long-term and effective improvements in cognition
of the advanced AD patients. If the therapeutic effect is short-lived, a second treatment will be applied to
reverse the cognitive decline after the end of the first 12-week treatment. The clinical trial research is entirely
for the development of innovative therapeutics that may advance progress in preventing and treating AD and
other AD-related dementias, a necessary and important phase IIa trial for the commercial development of
AD therapeutics. We anticipate that completion of this study would greatly facilitate progress in treating AD
and other AD-related dementias and speed-up the commercialization of the effective therapeutics into
market, thus paving the road toward successful outcomes in AD therapy.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10022520
- **Project number:** 5R44AG066366-02
- **Recipient organization:** SYNAPTOGENIX, INC.
- **Principal Investigator:** Miao-Kun Sun
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,732,392
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022520

## Citation

> US National Institutes of Health, RePORTER application 10022520, Long-term therapeutic effects of synthetic bryostatin-1 in advanced AD without memantine (5R44AG066366-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10022520. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*