In recent years, Huntington’s disease has joined the group of neurodegenerative diseases characterized by aggregation of the tau protein in fibrillary tangles inside neurons.
An invention by Prana Biotechnology might give new insights into the disease processes and allow for new drug candidates to be screened for activity against the disease. The tool, originally aimed at Alzheimer’s disease and dubbed ‘Alzheimer’s-in-a-Dish’, also models Huntington’s disease and is now used to evaluate a drug developed for both conditions — the experimental drug PBT2 for lowering tau levels.
PBT2 is a molecule with the ability to both decrease protein aggregation and normalize levels of metal ions in the aging brain. Called ‘MPACs’ (Metal Protein Attenuating Compounds), they prevent the interactions between metal ions and proteins outside cells. Scientists believe that high levels of copper and zink speed up the aggregation of proteins.
The disease model, produced in 2014, was described in the journal Nature. Professor Rudolph Tanzi, founding scientist and chief scientific advisor for Prana, and his colleague Dr. Doo Yeon Kim of Massachusetts General Hospital and Harvard Medical School detailed how it successfully recreated Alzheimer’s brain damage in a three-dimensional tissue culture created with the help of stem cells. The model was later awarded the Smithsonian 2015 American Ingenuity Award.
Prana researchers have improved and evaluated the model for the purpose of drug screening. Data presented by Tanzi on July 26 at the 2016 Alzheimer’s Association International Conference (AAIC) in Toronto, showed that PBT2 reduced levels of phospho-tau aggregates in the model. The drug also improved the survival of neurons.
PBT2 was evaluated in a Phase 2 clinical trial of Huntington’s disease, where the drug was shown to be safe, well-tolerated, and did not create more side effects than placebo. The trial also showed that the drug improved cognition, particularly the ability to plan activities, an aspect of cognition referred to as executive function.
According to a press release, “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.”