Biotech Values

[SF Wolf]

mcbio, regarding Neurotrope's (NTRP) upcoming release of Ph2b AD study results in 147 moderate to severe Alzheimer’s patients due by the end of this month you ask: "Is there any strong independent data to suggest activating protein kinase C epsilon would work in AD?"

This study provides some context using NTRP's lead drug
Byrostatin -1 to restore synaptic loss, the underlying cause of AD according to Neurotrope:

Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury

"Bryostatin-1 has been successfully used in numerous animal models of neural injury including TBI, ischemic stroke, auditory neurodegeneration, and Alzheimer’s disease and is currently under investigation in clinical trials...For example, bryostatin-1 protects against loss of pre-synaptic synaptophysin and loss of post-synaptic spinophylin following TBI in mice... Likewise, bryostatin-1 decreased apoptosis and prevented deficits in synaptogenesis in a global model of cerebral ischemia..."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000781/


Also, the scholarly article below was referenced twice by Dr. Alkon, the lead researcher and CSO of NTRP in recent presentations at both the Oppenheimer and Sachs Forums. I believe for Dr. Alkon this study independently confirms an element of his theoretical framework for the role of PKC epsilon in modulating Alzheimer’s disease. This study addresses one aspect of the multi-modal effect of treatment with Byrostatin. The reduction of amyloid plaque pathology.

Briefly, the study took mice that genetically express AD at an early stage in their life cycle. Then this mouse model was further genetically manipulated with a gene to produce higher than normal levels of PKC epsilon (the brain agent that Byrostatin stimulates to treat AD). The premise was, will higher levels of PKC epsilon prevent AD symptoms in animals that always develop the disease.

This study showed that these double transgenic mice had lower amyloid plaque deposits and Alzheimer’s disease expression confirming an important theoretical aspect of Dr. Alkons work.

PKCe increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice
Choi et. al.
March 31, 2006

Abstract
Deposition of plaques containing amyloid ß (Aß) peptides is a neuropathological hallmark of Alzheimer's disease (AD). Here we demonstrate that neuronal overexpression of the e isozyme of PKC decreases Aß levels, plaque burden, and plaque-associated neuritic dystrophy and reactive astrocytosis in transgenic mice expressing familial AD-mutant forms of the human amyloid precursor protein (APP). Compared with APP singly transgenic mice, APP/PKCe doubly transgenic mice had decreased Aß levels but showed no evidence for altered cleavage of APP. Instead, PKCe overexpression selectively increased the activity of endothelin-converting enzyme, which degrades Aß. The activities of other Aß-degrading enzymes, insulin degrading enzyme and neprilysin, were unchanged. These results indicate that increased neuronal PKCe activity can promote Aß clearance and reduce AD neuropathology through increased endothelin-converting enzyme activity. http://www.pnas.org/content/103/21/8215.full