Alzheimer’s Therapy Candidate Bryostatin Generates New Synapses in Mouse Brains, Study Shows

Neurotrope Bioscience’s lead Alzheimer’s drug candidate, bryostatin, promotes the formation of new synapses in the brains of mice, according to the study, “PKC epsilon Promotes Synaptogenesis through Membrane accumulation of the Postsynaptic Density Protein PSD-95,” recently published in the Journal of Biological Chemistry.

Synaptogenesis and synaptic maturation are two common concepts in the field of neuroscience. While synaptogenesis is about the formation of synapses between neurons in the nervous system, synaptic maturation is related to a maturing process that synapses undergo from a young neuron (at this stage, they cannot receive synapses from other cells) to adult, mature neurons.

Previous reports showed the protein kinase C epsilon (PKCε) promotes both synaptic maturation and synaptogenesis. However, the full molecular mechanisms involving PKCε-mediated maturation were not fully understood. Another protein, called PSD-95, was also shown to lead to synaptic maturation.

In this study, researchers investigated the relationship between PKCε and PSD-95.

They discovered that bryostatin activates PKCε and increases the levels of PSD-95, targeting it to the neuronal membrane and enhancing synaptogenesis through PSD-95.

Two proteins, amyloid-beta and tau, established factors known to form toxic accumulates in the brains of people with Alzheimer’s disease, also reduce PSD-95. This reduction continues to be detected as the disease progresses.

Neurotrope Bioscience is funding a Phase 2b clinical trial to test the effectiveness of bryostatin in treating the causes and progression of Alzheimer’s disease.

“Dr. Sen, together with Dr. Tom Nelson, continue to reveal important new insights into the processes of brain degeneration and regeneration,” Dr. Dan Alkon, scientific director of BRNI (Blanchette Rockefeller Neurosciences Institute in Morgantown, West Virginia), said in a press release.

“Our studies consistently demonstrate that the synaptogenic growth factors such as BDNF, NGF, IGF, etc., are increased by bryostatin-induced activation of PKC epsilon. Bryostatin has the ability to regenerate the brain wiring lost in preclinical disease models and entirely restore memory capacity due to many causes of neurodegeneration such as Alzheimer’s, Fragile X, and TBI,” he said.

“This latest article provides major new evidence that BRNI is developing and Neurotrope is clinically testing bryostatin as a potential ‘universal’ therapeutic for neurodegeneration in the brain, however it arises, even due to disease genes as distinct as Fragile X, ApoE, and Presenilin,” Alkon said, referring to a BRNI review article published in Trends in Pharmacological Sciences.