Synaptogenix Inc (SNPX)

[Cyosol]

Looks like the Chinese are starting to show some interest in the Bryostatins:

https://pdfhost.io/v/BkncGb4U_wu2019pdf.pdf

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2.4. Bioactivities of Bryostatin 1 in Central Nervous System Diseases

As a PKC activator, bryo 1 effectively enhanced the expression and activation of the brain-derived neurotrophic factor in the hippocampus. Thus bryo 1 can improve learning and memory, and reverse depression. It is also a potential clinical therapeutic drug for neurodegenerative diseases such as Alzheimer's disease (AD), fragile X syndrome (FXS), and stroke. The preclinical research progress in these fields is discussed below.

Studies by Thomas J. Nelson demonstrated that bryo 1 could go through the blood-brain barrier (BBB) and activate PKC in the brain, including signal transduction enzyme PKCe, which is involved in learning and memory functions. Therefore, it could prevent/reverse the synaptic loss and promote synaptic maturation. Meanwhile, bryo 1 was well tolerated in patients in an anti-AD clinical trial, although there was a pharmacokinetic difference among individuals.

In 2014, Rosen analyzed the biological restorative effect of bryo 1 on BBB after single blast exposure by examining the degree of brain damage. It was found that bryo 1 could effectively repair the injury of BBB via up-regulating tight junction proteins (occluding, VE-cadherin and ZO-1) and modulating PKC isozymes.

FXS is a CNS disease resulting in intellectual disability caused by transcriptional silencing of neurons of the FMR1 (the X-linked gene fragile mental retardation 1) gene product. The deficiency in FMRP (fragile X mental retardation protein, a repressor of dendritic mRNA translation) leads to dysregulation of synaptically driven protein synthesis and impairments of intellectual, cognitive and behavioral functions. Many great efforts for finding effective therapy have been performed to treat FXS. In 2014, Alkon et al. reported that after treatment with bryo 1, the synaptic growth and cognitive ability, spatial learning and memory of adult FXS mice were effectively improved. The mechanism of bryo 1 on FXS was shown to be based on the restoration of the normal functioning of the hippocampus. This result opened a new avenue for bryostatin-like agents as new drugs to treat FXS even after the complete development of the postpartum brain.

Combined therapeutic effects of bryo 1 and exercise regime on stroke-induced paralysis were studied by Shimpo’s group. They found that in contrast to treatment with bryo 1 alone, combined therapy promoted the recovery via improvement in synaptic transmission efficiency. Further research on the mechanism of this compound revealed in 2016 that the combination therapy effectively increased serotonin (5-HT) levels and decreased 5-HT turnover, in contrast to exercise or bryo 1 alone. In this study the levels of 5-HT, a contributing factor to brain plasticity and therefore may facilitate paralysis recovery, were monitored in the perilesional cortex, a potential site for intracortical brain-machine interfaces that may restore motor ability after stroke. This conclusion supported the theory that the administration of bryo 1 in combination therapy would be beneficial for motor function recovery in stroke rehabilitation.

Multiple sclerosis (MS) is an inflammation of CNS, mainly driven by self-activated T-helper (Th) 1 and peripheral activation of Th17 lymphocytes, while diffuse activation of myeloid cells is a progression of MS and currently has no satisfactory treatment. In 2018, the researchers at John Hopkins University brought the hope for the treatment of MS, they discovered that bryo 1 could prevent the progress of MS.
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