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A biotechnology company plans to recruit 112 obese volunteers and treat them for six months with either the vaccine or a placebo while counselling them about healthy eating and encouraging them to take exercise.
At the end of the trial, the loss of weight in each group will determine whether the vaccine works. First results are expected in the second half of next year.
The vaccine consists of an antibody against ghrelin, a peptide (small protein) that regulates appetite. Injecting extra ghrelin into people makes them hungrier and encourages them to eat more.
Ghrelin has also been implicated in yo-yo dieting. Obese people who lose weight develop higher levels of ghrelin, which enourages them to eat more and put the weight back. A further clue comes from operations to reduce the size of the stomach: the technique is effective, if extreme, and there is evidence that it works in part because ghrelin levels are reduced as a result of the operation.
Cytos, the company undertaking the trial, believes that its vaccine will suppress ghrelin levels in obese people, lower their appetite and make it easier for them to follow a weight-reducing diet.
It is a therapeutic vaccine, rather than a preventive one, so repeated injections will probably be needed. However, once a stable lower weight has been achieved, treatment might be discontinued.
Animal experiments suggest that it may work. In mice, injections of the vaccine, known as CYT009-GhrQb, provoked high levels of antibodies against ghrelin. Vaccinated mice fed on a high-fat diet put on 15 per cent less weight than their unvaccinated litter-mates.
Cytos’s vaccine is the first to enter human trials against obesity, a potentially lucrative market. So far the drug industry’s efforts to tackle the obesity explosion have achieved limited success. Anti-fat drugs typically produce weight losses of only 5 to 10 per cent in less than half the patients who try them. Surgery works rather better, but has a death rate of up to 1 per cent, so is not a soft option. Cytos has two other vaccines in development — designed to treat nicotine addiction and high blood pressure.
Wolfgang Renner, chief executive officer of Cytos Biotechnology, said: “Obesity is on its way to becoming the leading cause of preventable death in Western countries such as the United States. Similarly to hypertension and smoking, obesity represents one of the most important risk factors for cardiovascular diseases, which account for almost 30 per cent of all global deaths. We are developing novel therapeutic vaccines that exactly address these major risk factors.”
The obesity vaccine will work by inducing the recipient’s immune system to create antibodies that bind to ghrelin and reduce the amount that reaches the brain. This should reduce the hunger signal and make it easier for obese people to stick to a weight-reducing diet.
Ghrelin evolved, scientists speculate, when mankind was subject to feast and famine. Those people whose genes promoted the gluttonous consumption of food when there was plenty were more likely to survive subsequent periods of famine.
This also explains why weight loss switches on the hormone, stimulating appetite. The body interprets weight loss as the onset of a famine and increases hunger to take full advantage of whatever food remains available.
Nobody yet knows whether ghrelin is the key to many cases of obesity, or just a few. An earlier discovery, the hormone leptin, which is an appetite suppressant, has turned out to be of limited use because most overweight people do not respond to it.
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