At the 15th International Virtual Conference on Alzheimer’s disease (AD) and Parkinson’s disease (PD) 2021, a clinical-stage biotech company based in New York, US Synaptogenix, presented its product bryostatin-1 for AD, a novel therapeutic designed to restore cognitive function and regenerate cerebral connections.
Bryostatin-1 is a protein kinase C activator, acting by targeting protein kinase C (PKC), that belongs to the family of natural marine cyclic macrolides. PKC epsilon activates endothelin converting enzyme (ECE), an enzyme that degrades beta amyloid. Activation of PKC blocks the process of degradation of beta amyloid and releases the nerve growth factors at neuronal synapses, which leads to improvement of memory. Bryostatin-1 is currently under Phase II of development for the treatment of AD; moreover, the company is working on the development of several other indications, such as multiple sclerosis and fragile X syndrome in Phase I, and PD, stroke, and traumatic brain injury in preclinical phase of development.
In a pilot study conducted by the company, bryostatin-1 was well tolerated and showed early signals of cognitive benefit. The trial was a double-blind, randomized, placebo-controlled Phase II, 12-week trial of bryostatin for 150 advanced AD patients between 55 and 85 years old, with Mini-mental state examination-2 (MMSE-2) of 4–15 and randomized into 20μg and 40μg bryostatin and placebo arms. The results showed that the safety profile was similar for both doses and placebo patients; however, primary improvement of Severe Impairment Battery (SIB) scores at 13 weeks was not significant (p = 0.134) in the full analysis set, although in the confirmation of acceptance for studies, the SIB comparison favored 20μg bryostatin compared to placebo patients (p < 0.07). Furthermore, a pre-specified analysis of covariance for baseline Namenda (memantine) blocking bryostatin and positive post-hoc trend analyses revealed statistical significance of p < 0.001.
After these results, in May 2020 the company announced the launch of a new long-term study of bryostatin-1 for the treatment of patients with AD. Currently the company has enrolled about a third of the patients, and this study is conducted in collaboration with the National Institutes of Health (NIH), which has awarded $2.7M in funding to the company to further investigate the therapeutic effect of bryostatin-1 in this patient population. This Phase II clinical study, which is expected to enroll approximately 100 patients, evaluates bryostatin-1 in the absence of Allergan’s Namenda for a 6-month period, which will include two 11-week dosing cycles. The study will focus on AD patients with moderately severe (MMSE-2 baseline score 14–10) and moderate (MMSE-2 baseline score 18–15) disease, and it will focus on assessing cognitive benefit measured by the SIB score. The company expects to read out about the trial in Q4 2022.
No new drug for AD has been approved in the past 18 years, despite more than 400 clinical trials and billions of dollars being spent in an attempt to tackle the disease. Pharma companies and researchers have understood the necessity and importance to look at different approaches and search other ways to treat the most important unmet needs in AD. In the absence of any proven disease-modifying therapy, the minute one became available, the rush to use it would be unmeasurable and the rewards in term of profits for the developer would be huge