Bryostatin

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"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- Bryostatin -

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Observations:

FDA Gives Clinical Trial Green Light On Drug To Treat Alzheimer’s Disease

Previous Studies Show Bryostatin Protects Against Alzheimer’s Protein, Rewires and Repairs Brain Damage

Morgantown, WV (April 22, 2009) - The Food and Drug Administration (FDA) has given the Blanchette Rockefeller Neurosciences Institute (BRNI) the go-ahead to conduct Phase II clinical trials of Bryostatin for the treatment of Alzheimer’s disease patients. The drug showed pre-clinical efficacy to not only treat Alzheimer’s disease symptoms, but also its underlying causes.

“We are very excited about the FDA’s agreement for BRNI to move forward with clinical trials,” said Dr. Daniel Alkon, Scientific Director of BRNI. “Bryostatin shows the promise to repair and protect against neurodegeneration caused by Alzheimer’s disease, stroke and other brain trauma, as well as enhance the brain’s normal memory functions.”

Bryostatin was originally created as an anti-cancer chemotherapy. When BRNI scientists extensively tested PKC activators against Alzheimer’s disease models, they discovered the drug’s hidden potential to stop Alzheimer’s disease.Over the past six years, the drug has shown remarkable possibilities. In preclinical testing, BRNI scientists experimented with Bryostatin on three species of Alzheimer’s disease transgenic mice, each species based on different human Alzheimer’s disease genes. The test results revealed that Bryostatin, and a related class of drugs discovered at BRNI, can reduce the toxic Alzheimer’s disease protein A Beta, restore lost synapses, and protect against the loss of memory functions. Bryostatin has been shown to enhance and restore memory by rewiring connections in the brain previously destroyed by stroke, head trauma, or aging itself.

The Phase II trials, slated to begin in approximately two to four months, will test these preclinical findings on human Alzheimer’s disease patients as well as controls, along with Bryostation’s effects on molecular targets in the human body, such as the signaling enzyme PKC. The drug’s side effects will also be carefully monitored using low doses that were previously found to be generally benign in human cancer patients.

Clinical trials for Alzheimer's drug at BRNI

Chestnut Ridge Center, West Virginia University’s psychiatric hospital, will conduct the trials on Bryostatin, a drug originally created as an anti-cancer chemotherapy...
http://backup.wvpubcast.org/newsarticle.aspx?id=10302

Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer's Disease
http://clinicaltrial.gov/ct2/show/NCT00606164

The Blanchette Rockefeller Neurosciences Institute Identifies Groundbreaking New Therapies for Prevention and Treatment of Alzheimer's Disease

MORGANTOWN, W.Va., Jan. 11, 2011 /PRNewswire-USNewswire/ -- A Blanchette Rockefeller Neurosciences Institute (BRNI) study published today in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in Alzheimer's Disease and identifies promising pharmaceutical solutions for the devastating condition... Alzheimer's Disease is not primarily a disease of plaques and tangles as many had previously concluded, it is most importantly a disease of synapses," said Dr. Daniel Alkon, the scientific director of BRNI and co-author of the study, "This study found that treatments that target the loss of synapses in the Alzheimer's brain, can virtually eliminate all other elements of the disease – elevation of the toxic protein, A Beta, the loss of neurons, the appearance of plaques, and loss of cognitive function; the animals' brains were normalized."...
http://www.prnewswire.com/news-releases/the-blanchette-rockefeller-neurosciences-institute-identifies-groundbreaking-new-therapies-for-prevention-and-treatment-of-alzheimers-disease-113303809.html

Morgantown, WV, January 12, 2011 – A Blanchette Rockefeller Neurosciences Institute (BRNI) study published today in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in Alzheimer’s Disease and identifies promising pharmaceutical solutions for the devastating condition that affects more than 5 million people in the United States. The BRNI study is the first to achieve fundamental molecular understanding of how synapses are lost in Alzheimer’s Disease before the plaques and tangles develop. At the same time, it is the first study to demonstrate the comprehensive benefits of synaptogenic compounds in treating Alzheimer’s Disease...
http://www.brni.org/news/articles/The_Blanchette_Rockefeller_Neurosciences_Institute_Identifies_Gr,46.aspx

PKC {varepsilon} Activation Prevents Synaptic Loss, A{beta} Elevation, and Cognitive Deficits in Alzheimer's Disease Transgenic Mice.
J Neurosci. 2011 Jan 12;31(2):630-43.
Hongpaisan J, Sun MK, Alkon DL.

Blanchette Rockefeller Neurosciences Institute at West Virginia University, Morgantown, West Virginia 26505, and Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Abstract

Among the pathologic hallmarks of Alzheimer's disease (AD) neurodegeneration, only synaptic loss in the brains of AD patients closely correlates with the degree of dementia in vivo. Here, we describe a molecular basis for this AD loss of synapses: pathological reduction of synaptogenic PKC isozymes and their downstream synaptogenic substrates, such as brain-derived neurotrophic factor. This reduction, particularly of PKC α and ε, occurs in association with elevation of soluble β amyloid protein (Aβ), but before the appearance of the amyloid plaques or neuronal loss in the Tg2576 AD transgenic mouse strain. Conversely, treatment of the Tg2576 mouse brain with the PKC activator, bryostatin-1, restores normal or supranormal levels of PKC α and ε, reduces the level of soluble Aβ, prevents and/or reverses the loss of hippocampal synapses, and prevents the memory impairment observed at 5 months postpartum. Similarly, the PKC ε-specific activator, DCP-LA, effectively prevents synaptic loss, amyloid plaques, and cognitive deficits (also prevented by bryostatin-1) in the much more rapidly progressing 5XFAD transgenic strain. These results suggest that synaptic loss and the resulting cognitive deficits depend on the balance between the lowering effects of Aβ on PKC α and ε versus the lowering effects of PKC on Aβ in AD transgenic mice.

PMID: 21228172 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/21228172

New Therapies for Prevention and Treatment of Alzheimer's Disease Identified

ScienceDaily (Jan. 14, 2011) — A Blanchette Rockefeller Neurosciences Institute (BRNI) study published in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in Alzheimer's Disease and identifies promising pharmaceutical solutions for the devastating condition that affects more than 5 million people in the United States...
http://www.sciencedaily.com/releases/2011/01/110112110739.htm

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