Nigel Hawkes, Health Editor
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British patients suffering from a rare disease will be among the first to try a new drug based on the “magic ingredient” in red wine.
A small trial in Newcastle upon Tyne will test resveratrol, a chemical that could lead to a whole family of new drugs with powerful effects against the diseases of ageing. The proprietary version of resveratrol, SRT501, is also under trial in India for use against diabetes and newer versions hundreds of times more powerful are in the pipeline.
The new drugs come from research showing that all species live longer on a calorie-restricted diet. So long as there is adequate nutrition, cutting calories by 40 per cent prolongs lifespan by 50 per cent or more – in yeast, mice, rats and every other species so far tested.
In 1999 David Sinclair, at Harvard, showed that a single gene, SIRT1, controlled the process. Subsequent work showed that resveratrol activates this gene – perhaps explaining why red wine seems to prolong healthy life. Dr Sinclair is now a director of Sirtris Pharmaceuticals, based in Cambridge, Massachusetts, which was set up to exploit the research. In 2006, working with Joseph Baur and others, he showed that in mice the ill-effects of a high-calorie diet could be reversed by resveratrol.
But this did not happen in mice lacking the SIRT1 gene, proving that this gene is the key to the process.
Sirtris developed SRT501 as a more potent version of resveratrol. The animal evidence suggests strongly that it – and its even more powerful successors – should work against the developed world’s fastest-growing degenerative disease, diabetes.
In mice and rats, SRT501 reduces weight gain and glucose levels in animals fed on a calorie-rich, Western-style diet. When used with existing diabetes drugs such as Met-formin, it amplifies the benefits. And, most strikingly, it increases the ability of the mice to run, turning them into athletes who can easily outlast their litter-mates on a treadmill.
SRT501 achieves this by increasing the production of mitochondria, the tiny power-houses within the cells, and amplifying muscle power. That is why the Newcastle trial has been set up. The 30 patients who will take part suffer from a progressive and fatal genetic disorder called Melas syndrome, affecting their mitochondria. Melas stands for mitochondrial encephalopathy, lactic acidosis, and stroke.
Symptoms vary greatly from patient to patient. “Some are benign, others devastating,” says Patrick Chinnery, Professor of Neurogenetics at the University of Newcastle upon Tyne and a specialist in mitochondrial diseases, who is running the trial.
Patients with Melas generally start by developing a form of diabetes. But the effects can later spread throughout their bodies.
“They can’t convert food into energy efficiently,” Professor Chinnery said. “It tends to affect the brain, the heart, and the limb mucles.”
The 30 patients in the trial will be divided into two groups, with half given SRT501 and half a placebo. The aim is to test safety and to investigate, using magnetic resonance imaging and muscle biopsies, whether the mitochondria are multiplied. Patients’ muscle strength and endurance will also be measured. “The animal evidence is quite compelling,” Professor Chinnery says. “I’m convinced it’s worth a go.”
There is a strong suspicion that mitochondria could also be involved in diabetes, a market worth more than $20 billion (almost £10 billion) a year. Peter Elliott, senior vice-president for drug development at Sirtris, says the company has gone to India for its first trials because the disease is exploding there and it wanted to test the drug in patients with new diagnoses who had not been treated with anything else.
A glass a day
— Many studies have linked moderate alcohol consumption with a reduced risk of heart disease
— There is less evidence that red wine is better than other forms of alcohol, but it is rich in antioxidants and resveratrol, the chemicals identified as providing the benefits
— Italian researchers claim it is good for the teeth and gums because of its antibacterial effects
— One glass a day – but not more – may slow the onset of dementia, according to another Italian study
— Swedish scientists found that wine, of whatever colour, made women’s heartbeat less variable
— But it’s not all good news: two large glasses a day increase the risk of bowel cancer by a quarter
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