News Release

Melbourne dementia discovery chosen for synchrotron testing

Peer-Reviewed Publication

Research Australia

The Australian Synchrotron experiment will play a pivotal role in helping scientists from Melbourne’s Howard Florey Institute and St Vincent’s Institute to analyse how recently identified compounds, which improve memory in rats, interact with the protein, called insulin-regulated aminopeptidase (IRAP).

Data from the experiment, which began on 6 June, will help the scientists refine the structure of these compounds so that they bind better to the IRAP protein, which is the next step in developing a drug that enhances and restores memory.

Dr Siew Yeen Chai from the Howard Florey Institute said these IRAP-binding compounds had already proven to be promising candidates for a drug to treat dementia and other forms of memory loss, including amnesia.

“Within five minutes of giving experimental rats a single injection of these compounds, the animals display a dramatically improved ability to run mazes, which is a standard memory test,” Dr Chai said.

Prof Michael Parker, an international leader in structural biology and Australian Research Council Federation Fellow at St Vincent’s Institute, was invited to submit projects for the Australian Synchrotron and chose his collaboration project with Dr Chai as one of the first proteins to be analysed at the new facility. For the past few months, Prof Parker’s team have been preparing a crystal form of IRAP bound to one of the promising compounds so it can be tested at the Australian Synchrotron.

Prof Parker said the synchrotron produces an extremely high intensity light beam that is used to see objects that are too small to be seen with a normal microscope.

“The beam will hit the IRAP crystal and will scatter to reveal the 3-D atomic shape of IRAP and show us how the compounds bind to and interact with IRAP,” Prof Parker said.

“Once we know how these compounds interact with IRAP, we can refine their structures so they bind more tightly, thus reducing the possibility of side-effects when the compounds are developed into a treatment for humans,” he said.

Around six years ago, Dr Chai and her Florey colleague, Dr Anthony Albiston, discovered IRAP, a specific protein in the brain that certain compounds act on to enhance learning and memory, as well as reverse memory deficits.

For the past four years, the Florey scientists, in collaboration with Prof Parker’s lab, have been searching for synthetic compounds that bind specifically to IRAP using a computer model of the protein.

Now the scientists are excited that the Australian Synchrotron experiment will speed up their drug-development research.

“The Australian Synchrotron is helping us to rapidly accelerate this research as we are able to collect, in hours, data on IRAP’s structure that would usually take months,” Prof Parker said.

“Access to the Australian Synchrotron also allows us to use smaller amounts of the scarce material being tested and provides an accurate protein structure,” he said.

This drug development project is being funded by a National Health and Medical Research Council drug development grant, Neurosciences Victoria, and the Institute for the Study of Aging in the US, but the Florey is now looking for a commercial partner to invest in this research.

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Dementia is a debilitating medical condition that is characterised by short-term memory loss and the most common form is Alzheimer’s disease. A recent report prepared by Access Economics revealed that the number of individuals with dementia in the Asia-Pacific region is estimated at 13.7 million in 2005. It is imperative that new effective treatments are developed to treat the disease and ameliorate the symptoms.

The Howard Florey Institute is Australia’s leading brain research centre. Its scientists undertake clinical and applied research that can be developed into treatments to combat brain disorders, and new medical practices. Their discoveries will improve the lives of those directly, and indirectly, affected by brain and mind disorders in Australia, and around the world. The Florey’s research areas cover a variety of brain and mind disorders including Parkinson’s disease, stroke, motor neuron disease, addiction, epilepsy, multiple sclerosis, and dementia.

St Vincent's Institute (SVI) is an independent medical research institute, which conducts laboratory research into the cause, prevention and treatment of high-impact diseases such as cancer, diabetes, obesity, bone diseases, Alzheimer's, cardiovascular disease and infectious diseases. SVI is affiliated with St Vincent's Hospital and the University of Melbourne.

The Australian Synchrotron is an accelerator-based light source located in Clayton, Melbourne. It produces fine beams of extremely intense light, including x-rays. Researchers from science and industry use the unique properties of this synchrotron light to analyse the molecular and atomic structure of samples with higher resolution and clearer data than can be achieved with conventional equipment. The Australian Synchrotron will officially open in the second half of 2007.


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