MELBOURNE, Australia & SAN FRANCISCO--(BUSINESS WIRE)--Prana Biotechnology Ltd (NASDAQ: PRAN) (ASX: PBT) today announced the article “The novel compound PBT434 prevents iron-mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease” was accepted for publication in the peer reviewed journal Acta Neuropathologica Communications. The peer reviewed article can be accessed from: https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-017-0456-2
The publication is the culmination of ten years of research from scientists at the Florey Institute of Neuroscience and Mental Health, (Melbourne, Australia), investigating compounds from Prana Biotechnology’s propriety chemical library. The novel drug candidate PBT434 is the first of a new generation of small molecules from the quinazolinone class of drugs that was specifically designed to block the accumulation and aggregation of alpha-synuclein, an abundant brain protein widely believed to be involved in the pathogenesis of Parkinson’s disease and related disorders.
Not only was PBT434 shown to block alpha-synuclein accumulation, but it also prevented loss of nerve cells in the region of the brain primarily affected in Parkinson’s disease, called the substantia nigra. To investigate the therapeutic potential of PBT434 to slow neurodegeneration, the researchers performed extensive animal testing in multiple Parkinson’s disease models, including tests in mice that over-expressed the alpha-synuclein protein. These results showed that PBT434 lowered alpha-synuclein and its toxic effects and simultaneously improved motor performance.
If these findings are also observed in patients with diseases caused by alpha-synuclein, PBT434 could address a significant unmet medical need in preventing their progression.
The key findings from the publication in Acta Neuropathologica Communications are:
- PBT434 prevents the formation of toxic alpha synuclein fibrils.
- PBT434 prevents the formation of insoluble alpha synuclein in animals.
- PBT434 prevents alpha synuclein mediated oxidative stress that induces cell death.
- PBT434 protects against cell death and preserves neuronal circuitry in both transgenic and toxin mouse models of Parkinson’s disease.
- PBT434 improves motor behaviour in Parkinson’s disease mouse models.
- PBT434 normalises brain iron distribution.
David Stamler, M.D., Prana’s Chief Medical Officer and Senior Vice President, Clinical Development said: “These findings are important because Parkinson’s disease and the related synucleinopathies cause significant disability and diminish the independence of afflicted individuals. An agent which slows disease progression could have a great impact on reducing disease burden and improving quality of life. We are eager to begin clinical testing of PBT434.”
The required animal testing has been completed and PBT434 is expected to begin human testing in a Phase 1 trial later this year.