Nigel Hawkes,
Health Editor The London Times
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.
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.
