Bryostatin-1 effective for Alzheimer's disease

Preliminary phase 2 study findings indicated efficacy of Bryostatin-1, a protein kinase C epsilon activator, for moderate-to-severe Alzheimer’s disease.

“These results, which show improvement in patients with moderate to severe Alzheimer's disease, the population that is generally recognized as the most difficult to treat, provide exciting evidence of a new therapeutic approach potentially could rejuvenate synaptic networks in the brain. Improvements across the range of important manifestations of the underlying neurodegenerative disease, as shown in this phase 2 study, could potentially represent a shift in the paradigm to treat Alzheimer’s disease,” Daniel Alkon, MD, president and chief scientific officer of Neurotrope, said in a press release.

To assess safety and efficacy of Bryostatin-1 for moderate-to-severe Alzheimer’s disease, researchers conducted a phase 2 study comparing 20 µg and 40 µg of Bryostatin-1 with placebo among 147 individuals with late-stage Alzheimer’s disease. The primary endpoint was Severe Impairment Battery (SIB), measured after 12 weeks of treatment. The study cohort had a mean age of 72 years.

Study participants in the completer population (n = 113) met the primary endpoint, while those in the modified intent-to-treat population (n = 135) did not.

Among participants who received 20 µg of Bryostatin-1, participants in the completer population exhibited a mean increase in SIB scores of 1.5, compared with a 1.2 increase in the modified intent-to-treat population and decreases of –1.1 and –0.8 in the placebo groups.

Compared with placebo, participants who completed the study (P < .082) and in the modified intent-to-treat population (P < .104) exhibited better improvement on the Alzheimer Disease Cooperative Study-Activities of Daily Living Inventory, Severe Impairment version.

Participants who received 20 µg pf Bryostatin-1 had higher incidence of diarrhe compared with the placebo group.

Adverse events were more commonly reported in participants who received 40 µg of Bryostatin-1 than those who received 20 µg.

Analysis of the phase 2 findings is ongoing, according to the release.

Once all analyses have been reviewed, Neurotrope plans to meet with the FDA to discuss clinical and regulatory pathways for Bryostatin-1.

“The results of this relatively small randomized, double-blind, placebo controlled study of Bryostatin-1 shows that Bryostatin-1 has the potential to positively impact the lives of these severely debilitated patients with moderate-to-severe [Alzheimer’s disease], a population that is in dire need of new therapies, especially drugs with a new mechanism of action,” Susanne Wilke, PhD, CEO of Neurotrope, said in a press release. “We are excited to take the next steps in advancing the development of Bryostatin-1 to treat this serious disease that every year becomes a larger and larger public health burden in the U.S. and around the world. Additional development, with a path to phase 3, is clearly warranted.”