Alzheimer’s disease is the most common form of dementia, accounting for 60%-80% of all cases. Neurotrope has conducted the first placebo-controlled, Phase 2 trial of a protein kinase C epsilon (PKCɛ) activator for the treatment of Alzheimer’s, which in preclinical studies induced the growth of new synapses and prevented neuronal death. Recent clinical trial data showed sustained increase in Severe Impairment Battery measures and improvement in cognition, suggesting the drug may treat the progression of AD, rather than just symptoms. A confirmatory trial will commence in 2018.
Fragile X syndrome is a genetic disorder that causes developmental delays, intellectual and learning disabilities, anxiety, and autism spectrum disorders. FXS affects 135,000 in the U.S. alone. Bryostatin-1 for Fragile X has been designated as an orphan drug, and in animal models, was shown to restore synaptic networks, rectify memory deficits, and reverse biochemical abnormalities. Neurotrope preclinical data, in a collaboration with the FRAXA Research Foundation, showed that Bryostatin-1 significantly improves autism spectrum abnormalities. Neurotrope plans to initiate clinical testing of FXS patients in 2018.
Niemann Pick Type C is both a debilitating and lethal disease, affecting about 35,000 children per year. Neurotrope is working with world renowned experts at the Icahn School of Medicine, Mt. Sinai to develop its lead compound, Bryostatin-1, as a potential treatment for the excessive accumulation of cholesterol and other lipids in the viscera and brain resulting in cell death and to neuologic symptoms, including difficulty in swallowing and speaking, loss of coordination, seizures, and progressive dementia. There is no FDA approved treatment for Niemann-Pick Type C.
|PKC epsilon Promotes Synaptogenesis through Membrane Accumulation of the Postsynaptic Density Protein PSD-95 J Biol Chem. 5;291(32):16462-76, 2016 Abhik Sen, Jarin Hongpaisan, Desheng Wang, Thomas J. Nelson and Daniel L. Alkon|
|Rescue of Synaptic Phenotypes and Spatial Memory in Young Fragile X Mice. J. Pharmacol. Exp. Ther. 357: 300-310, 2016Miao-Kun Sun, Jarin Hongpaisan, and Daniel L. Alkon|
|ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation Neuroscience 35(19): 7538-7551; doi: 10.1523 /JNEUROSCI. 0260-15.2015 Abhik Sen, Thomas J. Nelson and Daniel L. Alkon|
|Apolipoprotein E3 (ApoE3) but Not ApoE4 Protects against Synaptic Loss through Increased Expression of Protein Kinase Cε. J Biol Chem 287(19), 15947-15948, 2012. Sen A, Alkon DL, Nelson TJ|
|PKCε Activation Prevents Synaptic Loss, Aβ Elevation, and Cognitive Deficits in Alzheimer's Disease Transgenic Mice, Journal of Neuroscience, 31(2):630–643, 2011. Hongpaisan, J., Sun, MK, Alkon DL|
|Postischemic PKC activation rescues retrograde and anterograde long-term memory. (Proc Nat. Acad. Sci. USA) 106 (34): 14676–14680, 2009. Sun, MK, Hongpaisan, J, Alkon, DL|
|A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC. Proc Natl Acad Sci USA 104 (49): 19571-19576, 2007. Hongpaisan J, and Alkon DL|
|Towards universal therapeutics for memory disorders. Trends in Pharmacological Sciences, June 2015, Vol. 36, No. 6. Miao-Kun Sun, Thomas J. Nelson, and Daniel L. Alkon|
|PKC activator therapeutic for mild traumatic brain injury in mice. Neurobiology of Disease 41 (2011) 329–337. Ofer Zohar, Rotem Lavy, Xiaomei Zi, Thomas J. Nelson, Jarin Hongpaisan, Chaim G. Pick, D.L. Alkon|
– George Perry, Ph.D., Professor of Neurobiology and Dean of the College of Sciences at The University of Texas at San Antonio
Charles Ryan, J.D., Ph.D.
Director & CEO
George Perry, Ph.D.
Ivan Gergel, M.D.
Martin R. Farlow
Paul Coleman, PhD
Daniel F. Hanley Jr. MD
Marwan Sabbagh, MD
Lee Jen Wei, PhD
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Sam Martin / Ryan Baker