Protein shows promise of liver disease cure

By SIMON COLLINS science reporter

Auckland University scientists have discovered that a naturally occurring "anti-fat" protein can cure liver diseases caused by over-eating and drinking.

The breakthrough offers a potential treatment for thousands of New Zealanders with obesity or alcohol-related diseases.

Researchers are now raising $20 million to start human trials.

The team, led by Professor Garth Cooper, has found that injections of the protein can drastically cut the number of fatty liver cells in mice that have been fed on alcohol or high-fat diets. Other researchers have found that the protein can reduce weight, cut blood sugar levels and overcome resistance to insulin in mice with diabetes.

If the same results can be achieved in humans, the protein offers potential treatments for a wide range of diseases associated with alcohol, obesity and lack of exercise, such as heart disease and Type 2 diabetes.

Those two diseases alone kill 4600 New Zealanders a year - slightly more than cancer, and accounting for one-third of all deaths.

Chronic liver disease, also often associated with alcohol and obesity, is the 10th-biggest cause of death in the United States, and this month's US-based Journal of Clinical Investigation has put the Auckland breakthrough with the disease on its cover. "There are no effective therapies," Dr Cooper said.

"You can try to stop drinking, but many people can't do it, and even then, in the later stages of the disease the liver doesn't recover.

"We can make the liver recover. This is the first time in the history of medicine that it has been done."

The protein in question, adiponectin, is a hormone, or "signalling" protein, which is made by fat cells to regulate the body's absorption of food.

A post-doctoral researcher in Dr Cooper's laboratory, Chinese-born Dr Aimin Xu, 36, has found abnormally low levels of the hormone and high rates of liver disease in 90 obese people in Hong Kong - suggesting that the protein might have the same effects in humans that it has in mice.

Dr Cooper is now negotiating with Auckland-based financier Birnie Capital Partners (formerly FR Partners) to raise about $20 million for human trials with adiponectin and other potential drugs through his research company, Protemix.

Dr Cooper himself has put in "several million" dollars from selling his shares in Amylin Pharmaceuticals, which he founded to develop diabetes drugs in the United States in 1987. That company is now worth about US$2 billion ($3.4 billion).

"Our objective ultimately is to build a New Zealand-based biopharmaceutical industry here," he said. "We will succeed, I have little doubt of that."

Dr Xu's wife, Yu Wang, who gained her own doctorate this week after 2 1/2 years' study with Dr Cooper, said Dr Xu's research on human patients was done in Hong Kong because of its population density.

"It's a collaboration between China and here, using the big population advantages of China and the advanced technology here," she said.

The Hong Kong study was funded by Hong Kong University.

Protemix has a $10.8 million grant from New Zealand's Foundation for Research, Science and Technology to research several potential drugs, and has just won a six-year, $4.8 million grant from the Health Research Council.

Bill Birnie, of Birnie Partners, said the $20 million being raised from the company's investors and institutions would be used at first for trials of a potential diabetes drug labelled GC811007, which had just completed phase two human trials centred at Middlemore Hospital.

Dr Cooper said the US Food and Drug Administration had agreed to consider that drug on its "fast-track" approval process. A multinational chemical synthesis company will be involved in the next stage, but Dr Cooper hopes to keep part of the drug manufacturing process in New Zealand.

A professor of medicine and human nutrition at Otago University, Dr Jim Mann, said that the research on adiponectin was still at an early stage.

"There is a lot of interest in adiponectin, absolutely so.

"But one has to be very careful about extrapolating what happens in mice to men," he said.

He was wary of "breakthroughs". "I think we should have the data before we say we have the answer."