Human brain

The announcement was made at a Parkinson’s Disease and Movement Disorders conference in Sydney on 20 June 2013. Prana Biotechnology says the drug shows “significant disease-modifying capability in multiple animal models of Parkinson’s disease with potential utility in a range of movement disorders”.

The role of dopamine

Parkinson’s is a degenerative condition that affects the central nervous system and is caused by the death of neurons in the region of the brain called the substantia nigra. In Parkinson’s disease, iron is able to bind with dopamine (in the substantia nigra), preventing it from functioning normally. Dopamine acts as a neurotransmitter, enabling smooth, quick, coordinated movements. Conversely, lack of available dopamine causes the awkward movements and tremors characteristic of Parkinson’s.

The iron can also bind with alpha synuclein proteins causing them to aggregate. The aggregation of this protein is a well established pathological feature of Parkinson’s and a target for new disease-modifying therapies.

The researchers say PBT434 prevents alpha synuclein from aggregating and also prevents the toxic consequences of iron combining with dopamine.

Preservation of neurons

In a further sign of the potential of PBT434 as an effective treatment, its therapeutic benefits were seen to be dose dependent. Increasing increments of the drug resulted in increased preservation of neurons and increased improvement in motor function.

“These data are highly positive and support the advancement of PBT434 as a first-in-class drug that could change the course of Parkinson’s disease and related movement disorders,” says Geoffrey Kempler, Prana’s Chairman and CEO, in a press release from the company. “This would be a major step forward in therapy as existing treatments are focused on symptomatic relief and offer little in the way of halting neurodegenerative decline once it has begun. The drug is progressing through the development process, with the aim of first clinical trials in 2015.”

The findings were presented by Professor Colin Masters, Director of The Mental Health Research Institute at The Florey Institute of Neuroscience, in a plenary presentation, and Associate Professor David Finkelstein, Head of the Parkinson’s Disease Laboratory also at The Florey Institute.

“What we have known for some time is that dopamine and iron together in the brain form a combustible mix and this drives alpha synuclein aggregation and toxicity,” said Professor Finkelstein.

PBT434’s modes of action

“What we’ve seen with PBT434 is two beneficial modes of action – it prevents cell death by inhibiting the interaction between dopamine and iron and it also stops this accumulation of alpha synuclein.”

Professor Finkelstein said this is the first molecule designed to inhibit the neurotoxic build-up of alpha synuclein in the brain, and PBT434 could support the “next generation for PD [Parkinson’s disease] therapies”.

According to Parkinson’s New Zealand, approximately 1 in 500 people are living with the condition. While it generally affects older people, approximately 10% of the population diagnosed with Parkinson’s are under the age of 40 – it can and does strike anyone, including, in rare instances, children. The average age at diagnosis is 59.