Prana touts development as possible Alzheimer's therapy

By Graeme O'Neill
Wednesday, 10 September, 2003

Melbourne-based biomedical company Prana Biotechnology (ASX:PBT) has announced it has developed a set of assays for high-throughput testing of molecules with therapeutic potential for Alzheimer's disease.

The assay will rapidly identify molecules that exhibit strong copper-chelating activity. Prana has already used it to identify a new lead compound, PBT2, which on all measures, appears to have more potent activity that the company's original candidate therapy, the disused antibiotic clioquinol.

In the late 1990s, Prana's co-founder, Dr Ashley Bush, showed that copper ions play a key role in the aggregation of molecules of beta-amyloid, the protein fragment that forms nerve-killing deposits called amyloid plaques in Alzheimer's-affected brains.

In a key experiment, he showed that clioquinol could dissolve amyloid plaques in vitro, by capturing and sequestering the copper ions that bind the beta amyloid fragments together.

Prana's chief operating office, Dr Ross Murdoch, said the new assay system incorporated an improved version of this test.

It also tests for a candidate molecule's ability to inhibit production of hydrogen peroxide - the copper ions in amyloid plaques catalyse the formation of hydrogen peroxide, which, in decomposing, spins out hydroxyl radicals, highly reactive molecules that intoxicate, then kill, neurons in the brain.

A third test checks whether a candidate molecule is potentially neurotoxic.

Murdoch said Prana has tested PBT2 in a transgenic mouse model of human Alzheimer's disease, and it is "doing all the right things". The company expects to begin clinical trials before the end of next year.

He said the molecule came out of 300 candidates screened. Prana is now making the assays available to other drug companies.

"Obviously, big pharmaceutical companies have huge libraries of compounds that might be good candidates for an Alzheimer's therapy," he said.

"We can test them very rapidly with our high-throughput assay, and if we find anything with interesting activity, there's potential for collaboration."

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