GSK award winner at forefront of quest for new kidney treatment

Start small, but think big, could be Melissa Little's motto. The kidney disease researcher, an associate professor at the University of Queensland's Institute of Molecular Bioscience, is hunting molecules that may stimulate failing kidneys to repair themselves -- but her ultimate goal is to be able to program stem cells to grow new kidneys from scratch.

Last night Little's 20-year quest was recognised when she received the prestigious, $50,000 GlaxoSmithKline Australia Award for Research Excellence for her development of new treatments for kidney disease.

At last night's award ceremony in Melbourne, Little told 300 eminent medical researchers, GSK executives and the Victorian treasurer and innovation minister, John Brumby, that there is an urgent need for new therapies, technologies and strategies to treat kidney disease.

Little said that currently, only one in four of the 7500-odd end-stage renal disease (ESRD) patients who receive kidney dialysis, at an annual cost of $375 million, will find a compatible donor for a kidney transplant.

The rest will remain on dialysis for life, which Little said was a poor substitute for having healthy kidneys. Dialysis provides only 10 to 15 per cent of the function of normal kidneys, necessitating long hours of treatment, hooked up to a dialysis machine.

And a dialysis machine doesn't provide the endocrine services of healthy kidneys, which include regulation of red-blood cell production, control of blood pressure, and maintenance of bone density.

Little, who originally trained as a cancer geneticist, began studying Wilm's Tumour, a form of kidney cancer, two decades ago, and showed that it was due to mutations that inactivate the Wilm's tumour suppressor gene, WT-1.

She has spent much of her career studying the molecular events involved in nephrogenesis -- the formation of the kidneys during embryonic development.

"The working hypothesis is that if we can fully understand the molecular basis of normal development, we should get a handle on how we can regenerate the kidney system," she said.

In recent years, Little has been assembling expression profiles of gene activity in the kidney during each phases of its development, and during normal kidney-repair processes. She has identified three lead molecules -- cytokines and cellular receptors -- that appear to have key roles in these processes. Two are cytokines that are involved in initiating the development of stem cells are kidney cells, the other enhances regeneration of ailing kidneys.

In 2002, the University of Queensland spun out a company, Nephrogenix, to commercialise the discoveries of Little's research group. The company is currently developing techniques to isolate kidney stem cells and growth factors.

None of the compounds is yet in pre-clinical development, but Little said the company already had a research partnership with a pharmaceutical company involving one molecule, and is looking for partners to develop the other two.

In situ repair is the easiest option, said Little, and likely to give Nephrogenix a faster and easier path to market.

"For many reasons, the idea of gene therapy scares the community, and the ethics of stem-cell therapy are still controversial," she said.

Asked whether she believed it would eventually be possible to grow new kidneys from stem cells, Little said she believed it would -- but said new kidneys grown in vitro, or even in vivo, would not be replicas of normal kidneys, either in form or function.

"But even to create a facsimile of a kidney with reasonable function would be an improvement over dialysis," she said.

Little chairs the Renal Regeneration Consortium, a group of a dozen experts in developmental biology, molecular genetics, bioinformatics and stem cell biology. The consortium is working to develop new technologies to repair kidneys damaged by chronic kidney disease.

Paul Lirette, the managing director of GSK Australia, said his company was delighted that Little had a track record of ground-breaking discoveries. But, he added, it was equally important that she had established a company to ensure the discoveries made by her research group could be commercialised and translated into better outcomes for patients.