Professor Rudolph Tanzi, Founding Scientist and Chief Scientific Advisor for Prana Biotechnology, presented results obtained from testing PBT2, Prana’s lead candidate for Huntington and Alzheimer’s diseases, at the Alzheimer’s Association International Conference (AAIC) in Toronto, Canada on July 26, 2016.
The presentation is entitled: “Reconstructing Alzheimer Amyloid and Tau Pathology in 3D Cell Cultures Derived from Human Stem Cells.”
In October, 2014, Professor Tanzi and his colleague Dr. Doo Yeon Kim of Massachusetts General Hospital/Harvard Medical School reported in the journal Nature that they successfully recreated Alzheimer’s disease pathology in an organoid consisting of human stem-cell derived neurons grown in 3D cultures. The landmark disease model, awarded with the Smithsonian 2015 American Ingenuity Award, exhibited beta-amyloid plaque deposition, neurofibrillary tangles and neuronal cell death, all major hallmarks of Alzheimer’s disease. The ‘Alzheimer’s-in-a-Dish Model’ provided the first proof of concept that beta-amyloid is sufficient to trigger neurofibrillary tangle formation.
Since that time, the inventors have been expanding and further validating the model for drug screening. At the AAIC 2016 meeting, Professor Tanzi reported testing results with PBT2 in the ‘Alzheimer’s-in-a-Dish Model’. He found that treatment of the 3D model cells with PBT2 significantly reduced levels of both phospho-tau (p-tau) aggregates and Aβ42 fibrils when compared to controls, also visible with immuno-staining. PBT2 also led to modest improvements in neuronal cell viability in the model.
Professor Tanzi reported that PBT2 testing in the 3D model resulted in dose-related, statistically significant reductions in p-tau (40 to 56%) and soluble Aβ42 (31 to 51%). PBT2 testing also resulted in statistically significant reductions in p-tau/total tau and insoluble Aβ42 ranging from 34% to 37% and 31% to 46%, respectively.
PBT2 comes from a library of over 2,000 compounds which Prana is evaluating separately for various indications. The 3D Alzheimer’s model adds to the body of evidence that PBT2 significantly reduces both p-tau and Aß42.
Based on Prana’s prior pre-clinical and clinical testing and these new results, PBT2 appears to carry great potential for targeting both the proteins at the root of Alzheimer’s; Aß42 and p-tau. p-tau also plays a role in other neurodegenerative disorders, such as Huntington disease.
Source: Prana Biotechnology