Clinical Trials

Bryostatin – Phase II Clinical Testing of a non-toxic PKC Activator

The Food and Drug Administration (FDA) has given Blanchette Rockefeller Neurosciences Institute (BRNI) permission 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.

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 and the deposits of A Beta called amyloid plaques, restore lost synapses, and protect against the loss of memory functions. In related preclinical testing, 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 will test these preclinical findings on human Alzheimer’s disease patients as well as controls, along with Bryostatin’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.


New Compounds for Clinical Testing


Based on a large body of basic research on animal models as well as the potent and specific efficacy of Bryostatin for AD models, BRNI scientists synthesized an entirely new class of PKC Activators that activate the PKC enzyme at a different molecular site. These new drugs show highly specific and potent activation of one specific form of PKC know as PKC epsilon.  It is this isozyme that most directly controls synaptogenesis as well as protects against the toxic protein, A Beta, of AD.  These PKC epsilon activators are metabolized to substances that are already present in the diet but that lack the PKC activating capacity.  However, as metabolites they are non-toxic and thus support the lack of toxicity of this new class of drugs.  These PKC epsilon-specific drugs, like Bryostatin, offer the potential of treating a variety of neurologic memory disorders as described above through their “neurorescue” properties of inducing the growth of new synapses, i.e. synaptogenesis, and preventing the loss of dying neurons.


Other Classes of New Drugs to Treat Neurological Memory Disorders


Using the same application of basic molecular research on cognitive functions of the brain, BRNI scientists have developed other drug classes with other molecular targets and the potential to treat other disorders such as Attention Deficit Disorder, Post-Traumatic Stress Disorder, and Mental Retardation. These efforts have already produced new drug classes and will be the basis of new drug optimization programs and clinical trials in the future.


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