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news.Prana Biotechnology has entered into a research collaboration with Takeda Pharmaceuticals International to study the potential of its investigational movement disorders compound, PBT434, to slow or prevent neurodegeneration of the gastrointestinal system.
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One of the important non-motor features of Parkinson’s disease is often the early presentation of severe and disabling impairment of gastrointestinal function.
Parkinson’s disease is characterised by the loss of neurons and their networks in the brain and in the gut.
The cause of neurodegeneration and gastrointestinal dysfunction in Parkinson’s disease is not known, but the protein alpha-synuclein has been hypothesized to be implicated in this process
Prana recently announced the publication of results with PBT434 demonstrating significant reduction of alpha-synuclein in various pre-clinical models of Parkinson’s disease in the paper entitled, “The novel compound PBT434 prevents iron-mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease” in the peer reviewed journal Acta Neuropathologica Communications. This paper suggested that PBT434 may reduce the formation of toxic alpha-synuclein fibrils and aggregates, rescue neurons burdened by such toxic forms of alpha-synuclein and restore motor function in animal models.
The research collaboration will investigate the ability of investigational compound PBT434 to mitigate gastrointestinal dysfunction; constipation, lowered colon motility and inflammation in mouse models, including an alpha-synuclein transgenic mouse.
Associate Professor David Finkelstein, Prana’s Senior Scientific Consultant and Head of the Parkinson’s Disease Laboratory at the Florey Institute of Neuroscience and Mental Health (Melbourne), said: “This early research is important because our major therapeutic objective is to treat these disabling symptoms and provide an early therapeutic intervention for both motor and non-motor Parkinsonian symptoms in patients which may significantly impact on the quality of life.”
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 and is expected to begin human testing in a Phase 1 trial later this year.