A hundred years after Alzheimer's disease was discovered, a cure for the degenerative condition that strips sufferers of their memory and personality remains a dream. The main advances have been in drugs to control symptoms such as agitation and restlessness. Restoring memory and cognitive ability has proved much harder.
That is why the publication last week of research showing that an old Russian drug once prescribed for hay fever may be the most effective treatment yet for the devastating condition has captured the attention of scientists and patients' groups.
A single 20mg pill of the drug, called Dimebon, taken three times a day, appears to be twice as effective in improving cognitive performance and preventing deterioration in memory as existing drugs.
The discovery was greeted by charities as perhaps the most exciting development in treatment of the disease. Existing drugs – cholinesterase inhibitors such as Aricept – have limited effects and were introduced over a decade ago.
According to the American researchers who led the trial, Dimebon is the furthest advanced of 65 agents being investigated for Alzheimer's, and holds the most promise.
However, British experts cautioned that the results were from a single trial of the drug, which is not licensed for Alzheimer's, and said further studies were necessary. A second international trial of the drug, which started last month in the USA, Europe and South America, is due to be completed by the end of the year.
Dimebon was used as an antihistamine in Russia 20 years ago, but it was withdrawn from the market when newer drugs superseded it. Investigations by the Russian Academy of Sciences revealed that it had a potential neuroprotective effect and it was bought by a US company, Medivation.
The company asked Professor Rachelle Doody, director of the Alzheimer's and Memory Disorders Center at the Baylor College of Medicine in Houston, to lead the randomised trial run by American and Russian scientists. It involved 183 patients with mild to moderate Alzheimer's in 11 hospitals in Russia.
Doody, who set up the Houston centre in 1987, is one of the world's leading researchers on Alzheimer's. She was the lead investigator in the trials of Aricept, the best-known existing Alzheimer's drug.
The results of the Dimebon trial she led, published last week in The Lancet, show that it improved performance on all five rating scales used to assess Alzheimer's patients, including cognitive performance, behaviour and capacity to carry out ordinary daily activities. Patients taking the drug scored better than they did at the start of the study, while those taking placebo got worse over the initial six-month period of the trial.
In a smaller group of patients who continued with the drug for a further six months, an even greater gap of 6.9 points on the cognitive performance test opened up between those on the drug and those on placebo. This compares with a 2.5- to three-point gain in trials of existing drugs.
Doody said: "I was surprised that all five of the outcome measures were positive and that the benefit [against placebo] widened over time. You don't see that with the other drugs... But this wasn't a comparison study – you can't say that makes Dimebon better than the other drugs."
She added: "I am very happy with the results. They show a clear signal and I am hopeful that the new international study which started last month will replicate them. US regulators have indicated that the trials are potentially acceptable as evidence for approval [for a licence]. There are a couple of dozen agents I am working on, and 65 that I follow, and the good news is that this is the furthest along in Alzheimer's research."
Clive Ballard of the Alzheimer's Society said the findings were "encouraging" and the discovery of a new application for an old drug was "potentially exciting". But it was a single trial of a small size and the results needed confirming, he said.
Caution was also expressed by Professors Alastair Burns of the University of Manchester and Robin Jacoby of the University of Oxford, who wrote in a commentary in The Lancet: "Addition of treatment options is good news for patients and clinicians – it promotes choice and offers the possibility of bespoke treatment packages which maximise the chances of response. [The] trial shows that Dimebon is better than placebo which is no mean feat considering the positive placebo responses in dementia."
But Jacoby said that he retained a "healthy scepticism" about the findings. "They need to be replicated before I will start prescribing it," he said.
If the results are replicated, it will be a boost for a new approach to drug research – taking old drugs and investigating their potential in other areas of medicine. Old drugs can go rapidly into clinical trials for new conditions because they are known to be safe. This speeds up development and cuts the cost.
A cure for Alzheimer's is not imminent, but it's good news that an old drug may be an effective treatment. Everything hangs on the second Dimebon trial now under way.
Alzheimer's: the facts
About 400,000 people suffer from Alzheimer's in the UK and 25 million worldwide.
It is the commonest form of dementia, costing £17bn in the UK for care and treatment.
The condition is caused by the accumulation of protein deposits in the brain, producing the dementia symptoms.
There are three drugs that claim to halt the progress of the disease (but not to reverse it) – Aricept, Reminyl and Exelon.
In 2006, the NHS's use of these drugs was restricted to the moderate stage of the disease by the National Institute for Clinical Excellence because of their limited effect.
There are currently no drugs available on the NHS for the tens of thousands of patients in the UK with mild Alzheimer's.