NZ scientist's gene research could be the answer to the obesity epidemic

A world-leading New Zealand researcher wants to start human trials of gene therapy to control obesity, after proving the technique in animal experiments.

Professor Matthew During, of Auckland University and Ohio State University in the United States, was the lead investigator of the ground-breaking animal trials. They are reported online today in one of the world's top medical science journals, Nature Medicine.

Based on the success of the animal trials, Professor During, a neuroscientist, wants to start human clinical trials.

"We believe we could be in the clinic with this approach within 12 months treating morbid obesity."

The treatment is similar to Professor During's gene therapy to the brain for Parkinson's disease, given under local anaesthetic, which is being used in phase 2 human clinical trials.

Obesity is a major problem throughout the West. In New Zealand, 26.5 per cent of adults are obese. The Ministry of Health is considering spending $16 million on obesity surgery for around 900 people each year who are extremely obese, because other treatments rarely work long-term in this group.

Obesity experiments by Professor During's team involved injecting up to three kinds of genetic material into the brains of various kinds of mice and measuring the effects on their body-weight and markers of diabetes.

The genetic material is injected into the part of the brain called the hypothalamus, after boring two holes through the skull. It is carried in a harmless virus whose genetic material has been replaced by the therapy.

The main active component is part of the human gene that causes the production of a substance called brain-derived neurotrophic factor (BDNF). This is a protein involved in weight regulation. It is coupled with genetic material that triggers auto-regulation of the BDNF to control the weight loss once the process is well under way.

A third genetic component was developed for a subsequent neurosurgery injection, if needed, to knock out the introduced BDNF gene as a rescue device that halts the weight-loss process.

In one of the trials, the body weight of obese mice reduced by 20 per cent in three weeks and stabilised for the remainder of the 11-week experiment.

The researchers noted suppression of food intake and increased energy output contributed to weight loss in diabetic mice given the gene therapy, but energy output - both at rest and from spontaneous activity - was considered the more significant factor.

Professor During said many genes had been found to be involved in obesity, but little had been achieved in converting that knowledge into effective treatments - until now.

"The efficacy and the degree of weight loss is very dramatic. We haven't seen that in any study previously ... We have very high expectations that this would also work in humans."