Dr. Daniel Alkon of Neurotrope BioSciences discusses the importance of partnering with Advocacy Groups such as the Fragile X Foundation for company. Neurotrope has reached out to advocacy groups for their clinical trial strategy for Bryostatin 1 for the treatment of patients with Fragile X Syndrome. Bryostatin 1 was granted by the FDA’s Office of Orphan Products Development in 2015.

A drug designated as an orphan must still undergo the regulatory review process to achieve marketing authorization, as with any other drug product in development. Sponsors of orphan drugs do, however, receive incentives from regulatory agencies and governments to encourage the development of such drugs. Bryostatin-1 activates Synaptic Growth Factors – BDNF, NGF, IGF, others. It also activates all amyloid-β Degrading Enzymes (ECE, Neprilysin, IDE). Bryostatin also activates α-secretase, which reduces formation of neurotoxic amyloid-β formed by γ-secretase and BACE. ApoE3 induces PKCϵ; by activating PKCϵ, so there is an increase in BDNF expression. Bryostatin blocks ApoE4 reduction of BDNF via HDAC inhibition. Bryostatin normalizes GSK3-β, thereby inhibiting pathological Tau protein transformation into neurofibrillary tangles (NFTs).

Studies have demonstrated that PKCϵ plays a pivotal role in learning and memory. Bryostatin, a small molecule, penetrates the blood-brain barrier and activates PKCϵ, resulting in Improved synaptic function, promotion of new synapse formation, maturation of immature synapses and repair of damaged synapses. PKCϵ protects against synaptic and neuronal loss, degrades toxic beta amyloid, enhances new synapses and memory, prevents neurofibrillary tangle formation. Preclinical work at BRNI demonstrated improved memory and learning in multple different Alzhiemer’s mouse models and several other animal models.