Prana to conduct Swedish trials of potential Alzheimer's treatment

Melbourne-based Prana Biotechnology has announced that it has received regulatory approval from Sweden's Medical Products Agency (MPA) to start a Phase IIa clinical trial of its proprietary lead compound, PBT2, in patients with early Alzheimer's disease.

The trial will be conducted in seven centres in Sweden.

The study, which will commence next month, will evaluate the safety and tolerability of PBT2. In addition, it will examine the drug's mechanism of action and indicators of potential efficacy in treating Alzheimer's disease. Results are expected to be announced in the fourth quarter of 2007.

Prana director Colin Masters, a University of Melbourne professor, said earlier clinical findings about PBT1, together with recent data on PBT2 in a mouse model, led the company to believe there may be biochemical and possibly even cognitive benefit in mildly affected patients.

"The best hope is that in the course of its development PBT2 could be shown to be disease modifying, offering real hope to Alzheimer's disease patients," Masters said. "Currently there are no approved disease-modifying treatments available to patients."

The Phase IIa study is a randomised, double blind, placebo-controlled design, in which 80 Alzheimer's disease patients will receive three months of either one of two oral dose levels of PBT2, or placebo.

In addition to examining safety and tolerability, the study will investigate the ability of PBT2 to affect multiple cerebrospinal fluid (CSF) and blood biomarkers of Alzheimer's disease during the treatment period. Outcomes will include measures of CSF A-beta and tau levels, as well as neurocognitive and behavioural changes.

Prana's co-founder, Professor Ashley Bush, recently told Australian Life Scientist magazine that mice improved markedly in Morris water maze tests less than a week after commencing once daily oral doses of Prana's PBT2 metal-protein-attenuating compound (MPAC).

Showing evidence of learning after five days of treatment, the mice performed virtually as well as normal mice in the Morris maze, a standard test of memory in the amyloid precursor protein (APP) gene mouse model of human Alzheimer's disease.

"Usually, a therapeutic intervention like the Alzheimer's vaccine takes many weeks, even months to show an effect," Bush said.

"With PBT2, we saw profound rescue of memory function within five days. By 10 days, they were basically operating like normal mice.

"The result was breathtaking, beyond anything we had expected."

Bush said the response of the mice to the experimental drug had provided new insights into the nature and progression of Alzheimer's disease.

"It's teaching us something that we had theorised - that there are two components to the disease. There is a loss of neurons, which may be irreversible. We don't expect to see neurons growing back.

"But we know that these mice don't lose many neurons, even though they show clear memory impairment. Their brain tissues contain lots of amyloid plaque, and we see clear symptoms of memory impairment, as well as synaptic pruning - the neurons are not forming many synapses.

"Most of the neurons remain alive; they're just not making as many connections as they should."

For the full story on Prana's lead compound, see Graeme O'Neill's story in the September/October issue of Australian Life Scientist, titled "Breathtaking results in Alzheimer's drug trial".