Australia’s Prana Biotechnology will demonstrate pre-clinical results of PBT434 as a novel therapeutic strategy for managing Parkinson’s disease during the 13th International Conference on Alzheimer’s & Parkinson’s Diseases, set for March 29-April 2 in Vienna.
The results will be presented in a poster, “PBT434 prevents neuronal loss, motor function and cognitive impairment in preclinical models of movement disorders by modulation of intracellular iron,” by David Finkelstein, PhD, senior scientific consultant to Prana and head of the Parkinson’s Disease Laboratory at Melbourne’s Florey Institute of Neuroscience and Mental Health.
The study included in vivo experiments showing that PBT434 protects against cognitive and motor dysfunction. It does so by preventing metal-mediated degenerative mechanisms. PBT434 counteracts the production of toxic reactive oxygen species that may damage lipids, proteins and DNA, and therefore disrupt cellular function. It also prevents an increase in misfolded forms of the protein tau, which form insoluble aggregates and lead to cell death.
The research team also observed that PBT434 prevents the iron-mediated accumulation of toxic aggregates of the protein alpha-synuclein, which are a pathological hallmark of Parkinson’s and currently being studied as a potential target for therapy.
Moreover, after oral administration to rats and dogs, PBT434 decreased alpha-synuclein in the cerebrospinal fluid (present in the brain and spinal cord), demonstrating that PBT434 therapy is capable of in vivo targeting of the central nervous system.
The results reveal that PBT434 has a strong toxicology profile and favourable therapeutic margin. Overall, PBT434’s neuroprotective effect and its ability to prevent the toxicity of tau and alpha-synuclein position it as a promising medication to treat Parkinson’s. Furthermore, Prana’s parallel studies shows that PBT434 induces beneficial effects on motor and cognitive function in various models of Parkinsonian disorders.
Prana is currently preparing PBT434’s pre-clinical development to initiate studies in humans. This adds to the company’s development of PBT2 for the treatment of Alzheimer’s and Huntington’s diseases.
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