Australian company Prana Biotechnology revealed pre-clinical results of a novel therapeutic treatment called PBT434 at the International Conference in Vienna recently. David Finkelstein, senior scientific consultant to Prana and head of the Parkinson’s Disease Laboratory at Melbourne’s Florey Institute of Neuroscience and Mental Health stated that “PBT434 prevents neuronal loss, motor function and cognitive impairment in preclinical models of movement disorders by modulation of intracellular iron.”
The study showed that PBT434 protects against cognitive and motor dysfunction by preventing metal-mediated degenerative mechanisms. PBT434 disrupts the production of toxic reactive oxygen species (free radicals) that damage lipids, proteins and DNA, leading to cellular dysfunction and prevents an increase in misfolded forms of the protein tau, which form insoluble aggregates and lead to cell death.
The research team also noted that PBT434 prevents the iron-mediated build-up of toxic aggregates of the protein alpha-synuclein, which are a pathological hallmark of Parkinson’s and subject of many studies. Furthermore, after oral administration to rats and dogs, PBT434 decreased alpha-synuclein in the cerebrospinal fluid, demonstrating that PBT434 therapy is capable of in vivo targeting of the central nervous system.
The results show PBT434 has a strong toxicology profile and favourable therapeutic margin. So, PBT434’s neuroprotective effect and its ability to prevent the toxicity of tau and alpha-synuclein place it as a potential medication to treat Parkinson’s. Prana’s parallel studies show that PBT434 induces beneficial effects on motor and cognitive function in various models of Parkinsonian disorders.
Prana is 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.