Prana's Anti-Parkinsonian compound PBT434 presented at 13th International Conference for Alzheimer’s & Parkinson’s Diseases
Prana (ASX PBT: NASDAQ PRAN) today announced a scientific presentation demonstrating pre-clinical evidence for Prana’s PBT434 as a first-in-class disease modifying therapy for the treatment of Parkinsonian movement disorders that will be featured at the 13th International Conference for Alzheimer’s and Parkinson’s Diseases in Vienna from 29 March 2 April 2017.
The poster entitled, ‘PBT434 prevents neuronal loss, motor function and cognitive impairment in preclinical models of movement disorders by modulation of intracellular iron’ will be presented by Associate Professor David Finkelstein, senior scientific consultant to Prana and Head of the Parkinson’s Disease Laboratory at the Florey Institute of Neuroscience and Mental Health in Australia.
The poster presents in vivo evidence of the ability of PBT434 to prevent the loss of neurons that underpin motor and cognitive dysfunction by preventing metal mediated degenerative processes that lead to neuronal death. For example, PBT434 intercedes in the production of damaging reactive oxygen species that are toxic to normal cellular function and the compound also prevents the accumulation of misfolded forms of the tau protein, which are known to promote cell death.
In addition to the beneficial impact of PBT434 on underlying neurodegenerative processes, the compound is also able to prevent the iron mediated accumulation of toxic aggregates of the protein alpha synuclein. Alpha-synuclein is of great interest to researchers because aggregated forms of the protein are considered a pathological hallmark of Parkinsonian conditions and are a recognised therapeutic target.
Importantly, when orally administered to rats and dogs, PBT434 reduced alpha-synuclein in the cerebrospinal fluid, which is present in the brain and spine, demonstrating the capability for PBT434 for in vivo target engagement. Collectively, the ability of PBT434 to promote neuronal health by reducing oxidative stress and preventing the toxic gain of function of both tau and alpha synuclein, positions PBT434 as a novel disease modifying agent.
From the comprehensive pre-clinical studies, PBT434 shows a strong toxicology profile and favourable therapeutic margin. Prana is preparing its pre-clinical development package for PBT434 to enable initiation of human studies.