 |
 |
 |
 |
 |
 |
||||
    | ||||
|
|
Obesity: a big problemWith more than 300 million sufferers worldwide, obesity is now a global healthconcern. But a Monash professor conducting research into obesity has developed a new class of drug that could make controlling the condition as easy as popping a pill, writes COREY NASSAU Associate Professor Frank Ng knows all about diabetes and obesity, but he is neither a diabetic nor overweight – he is a molecular biologist who has dedicated his life to understanding the causes, treatment and now prevention of diabetes. Dr Ng (above) first made news in 1969 while part of the Monash research team that discovered the benefits of using Human Growth Hormone (HGH) for the treatment of diabetes. Now, still working from the same office he has occupied for 30 years, Dr Ng is leading a team of researchers who have developed a weight control drug that has demonstrated, in animal trials, the ability to significantly reduce fat. The drug, developed in the Department of Biochemistry and Molecular Biology, is known as Advanced Obesity Drug 9604 (AOD9604) and can be administered orally or intravenously to control and treat obesity. Currently it is undergoing phase I human trials in the UK. It is estimated that almost one in two Australian men and one in three Australian women are overweight or obese, resulting in costs to the country’s health system of more than $1 billion annually and creating a booming weight loss industry. Manufacturers of an enormous range of ‘diet’ foods, owners of specialist diet and fitness centres all use aggressive marketing to attract the consumer dollar. But while research shows that Australians spend up to a million dollars a day on weight loss, much of it has little effect and the market is ripe for a solution to the problem. Dr Ng has spent much of his research career concentrating on the causes and treatment of diabetes, but it was his discovery while working with the peptide molecule HGH that sent him on a research path toward the ultimate treatment of that disease – its prevention. "There is an overwhelming link between obesity and the onset of type II or insulin-resistant diabetes," Dr Ng says. "So, by controlling the number of cases of severe obesity, you are also reducing the number of candidates who would be likely to develop diabetes." With this in mind, Dr Ng put his diabetes work on hold and turned his attention toward finding a means to control and treat obesity, a condition also associated with health risks such as cardiovascular disease, stroke, hypertension and certain types of cancer. "I have spent a lot of time focusing on HGH because I am interested in endocrinology, and this molecule has always fascinated me because of the complex actions it has on the human body," he says. "For the past five or 10 years, we have known that HGH has fat-reducing properties because we observed significant body fat reductions in children receiving hormone growth treatment to increase their height. "Unfortunately we were also aware that many people who used HGH developed type II diabetes. So although we knew a little, there was a lot about the mechanisms of this molecule that we still had to understand." Dr Ng believed the HGH molecule had many distinctive actions that likened it to the structure of a university where each faculty has one specific function and each department one specific discipline. With this concept in mind, his team started to dissect the HGH molecule – and suddenly they were getting answers. In the mid-1980s, the team had a breakthrough, finding two portions along the 191 amino acid long polypeptide that had potential for medical application. "The first portion we isolated was able to help control blood glucose levels – suitable for the treatment of diabetes – while the other was effective at making the animals in the trial use fat much faster and lose weight." Because research funding for the ‘diet pill’ was much easier to attract than funding for research into type II diabetes, the research team began spending countless hours in the laboratory to determine the structure of the portion they had isolated. Eventually they learnt how to replicate it chemically, and AOD9604 was born. According to Dr Ng, there is a general lack of understanding among the public about the management of obesity. "When you put on weight you increase the size of your fat cells, and when they reach a critical point, the body sends out a signal to produce more fat cells. Any chemical treatment, diet or exercise can only help you reduce the size of those cells," he says. "When fat cells multiply, a person cannot reduce the numbers of those cells without having them surgically removed." The Monash team has already done a lot of careful assessment on AOD9604 and is confident that it will achieve its purpose as a potential adjunct therapy for body weight control. "Because the drug is based on a peptide molecule, it will go into the body, send out a molecular signal, modify the metabolic events and then disappear. There is no build-up of the chemical, and we therefore see little chance of this analogue causing the side-effects that have plagued previous weight-control drugs on the market," Dr Ng says. With the support of Australian biotechnology company Metabolic Pharmaceuticals Limited, phase I human trials are under way to rule out any toxicity. From phase II forward, the trials will look at how effective the formulation is at reducing body fat. "We are hoping to give the drug to really obese people and reduce, to a certain extent, their fat so that they can become sufficiently mobile to begin the path towards improved health," Dr Ng says. "Obesity used to be a condition associated with the trend toward old age but now we are seeing more and more children suffering obesity. This group has become our greatest concern but hopefully, using drugs like this one, we will be able to prevent them from becoming obese adults." ACTION: To learn more about obesity or to access other nutrition and health information, visit the Monash Health Promotion site at www.med.monash.edu.au/healthpromotion/pamphlets/
|