Motor Neuron disease biomarkers and pharmacodynamics results

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PharmAust (ASX:PAA) has provided an update on the pharmacodynamic data from the Phase 1/2 trial of its lead drug candidate, monepantel (MPL) in Motor Neurone Disease.

The disease is believed to develop and progress as a result of neuronal inflammation and cell death due to the production of misfolded proteins in brain tissue.

PharmAust said that preliminary data from the trial indicate suppression of inflammation that may be responsible for the disease progression.

PharmAust’s executive chairman Dr Roger Aston said, “Molecular and cellular pathways of neurodegeneration in MND are complex. However, it appears that oxidative stress, protein misfolding and aggregation may be underlying causes for the inflammation associated in neurones during MND progression.

“Here we show that in Cohort 1 of oral monepantel in treating MND there is significant suppression of inflammatory markers. In preclinical studies we have shown that monepantel crosses the blood-brain barrier. These results bode well as we analyse markers that predict MND disease progression.”

Peripheral Blood Mononuclear Cells from the blood of all seven trial subjects enrolled in Cohort 1 have been collected at Calvary Healthcare Bethlehem in Melbourne and Macquarie University in Sydney. They were assayed at the Florey Institute of Neuroscience and Mental Health in Melbourne. Assays are looking for changes in protein levels of the mTOR pathway markers p-RPS6KB1 and p-EIF4EBP1.

The company said that assays show that MPL correctly targets these mTOR pathway markers in the blood, with five of seven participants having decreased p-RPS6KB1 levels and six of seven participants having decreased p-EIF4EBP1 protein levels.

The company said the demonstration of decreased p-RPS6KB1 and p-EIF4EBP1 levels is significant as it shows MPL correctly targets the pathway in the blood of people with the disease.