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Thursday, July 6, 2017

Prana’s Parkinson’s Therapy Candidate Shows Promise in Preclinical Studies .


Treatment with Prana Biotechnology’s investigational drug PBT434 showed potential in preventing neuronal death in a mouse model of Parkinson’s disease, according to a new study.
Results showed that PBT434 blocked the formation of alpha-synuclein aggregates, a hallmark of Parkinson’s, and normalized iron levels in the brain, thereby protecting neurons from damage.
Prana Biotechnology plans to start a Phase 1 clinical trial later this year to investigate the effects of PBT434 in humans with Parkinson’s disease.
Parkinson’s disease is characterized by the loss of a dopaminergic neurons, which produce the neurotransmitter dopamine, in a brain region called the substantia nigra. Death of these neurons affects the normal functioning of another brain region, the basal ganglia, which is responsible for voluntary body movements.
Several changes in the normal functioning of neurons are associated with the development of this disease, such as an abnormal iron distribution in the brain. Iron promotes the aggregation of alpha-synuclein, which is toxic to neurons and may cause their death.
Using mice with Parkinson’s disease, researchers observed that treatment with PBT434 improved brain levels of iron and prevented the formation of alpha-synuclein clumps. By doing so, it also prevented the toxic effects caused by the aggregated protein, such as oxidative stress, triggering neuronal loss. Oxidants damage other molecules within cells, such as proteins, lipids and DNA.
Indeed, PBT434 protected the neurons of the substantia nigra, the brain region rich in dopamine-producing neurons that is involved in movement coordination. The new compound also improved movement deficits in mice with Parkinson’s disease.
“These findings are important because Parkinson’s disease and the related synucleinopathies cause significant disability and diminish the independence of afflicted individuals,” David Stamler, MD, senior vice president and chief medical officer at Prana, said in a press release.
“An agent which slows disease progression could have a great impact on reducing disease burden and improving quality of life. We are eager to begin clinical testing of PBT434,” Stamler added.
The scientists who designed PBT434 work at the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia.

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