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A protein injection that decreases appetite helps obese monkeys to slim down fast and cuts their risk of diabetes.
Excitement is growing about a protein called GDF15, which naturally regulates body weight in humans and animals. When extra amounts are injected into mice, they eat less, lose weight and have fewer signs of diabetes.
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Several research teams have tried developing GDF15 as an obesity treatment, but it breaks down too quickly in the bloodstream to work.
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Now a team led by Murielle Véniant at pharmaceutical company Amgen has found a way to make GDF15 last longer in the body.
Dropping pounds
The team added an antibody fragment onto GDF15. Antibodies are immune proteins that help recognise foreign molecules in the body.
They found that this hybrid protein caused obese monkeys to eat about 40 per cent less. When given weekly injections, the monkeys lost 10 per cent of their body weight over 6 weeks. Their glucose tolerance also improved, making them less likely to develop type 2 diabetes.
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In comparison, the five obesity medications that are currently approved by the FDA for long-term weight management help patients to lose an average of 7 to 12 per cent of their body weight over the course of a year. Bariatric surgery – the gold standard for weight loss – usually results in 20 to 30 per cent weight loss in obese patients in the first year, but is expensive and can have complications and side-effects.
The GDF15 hybrid protein did not cause any noticeable side-effects in monkeys, Véniant says, although she adds that the study was designed primarily to assess how effective the drug is. Clinical trials will be needed to work out how well the treatment works in people, and if it causes side-effects like nausea, she says.
Gut-brain interaction
Injecting the protein into mice revealed that it binds to neurons in the stomach and intestines. These gut nerve cells send signals to the area postrema, a part of the brain known to reduce appetite and change dietary tastes.
When given the protein, mice were found to keep food in their stomachs for twice as long – which may make them feel fuller. Treated mice also chose to eat healthier food.
Amgen is not the only pharmaceutical company that is interested in targeting the GDF15 pathway. Since August, Janssen, NGM Bio, Eli Lilly and Novo Nordisk have all published papers in Nature studying GDF15’s role in regulating body weight. Janssen and NGM Bio have also announced they are testing a range of compounds similar to GDF15.
Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.aan8732
Read more: Let’s take a knife to the world’s rising tide of type 2 diabetes
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