Unprecedented Alzheimer’s drug slows disease by 80 per cent

Tangles in the brain


At last, there’s a drug that seems to have a big effect on the progression of Alzheimer’s disease. It took 30 years to develop, but the treatment has proven successful in a large trial of people with mild to moderate symptoms of the disorder.

“It is a significant event in the history of Alzheimer’s and dementia research,” Maria Carrillo at US charity the Alzheimer’s Association, says of the results, announced today.

The drug, called LMTX, is the first to produce really promising results in a large phase III trial, in which potential therapies are pitted against a placebo in hundreds of recipients. Drugs do already exist for Alzheimer’s, but these generally have only a modest effect.

“Our results are unprecendented, compared with anyone else’s,” says Claude Wischik  at the University of Aberdeen, UK, and co-founder of the firm TauRx Pharmaceuticals, which developed LMTX.

Improved independence

The trial involved 891 people who already had mild or moderate symptoms of Alzheimer’s disease. Some received LMTX alone, others took it in conjunction with other treatments they were already taking, and the rest received a placebo.

At the end of the 15-month trial, tests of mental ability revealed that those taking LMTX alone had deteriorated significantly more slowly than those taking placebo – both in terms of cognition, and their ability to continue carrying out every-day tasks, such as dressing and feeding themselves. “On the whole, [the drug] slowed progression by about 80 per cent,” says Wischik.

Those taking LMTX were more engaged with their families, and one couple said it had allowed their lives to re-start again, says Wischik. “A wife of a patient told me her husband suddenly got up and fixed the garden fence, which he’d needed to do for years,” he says.

MRI brain scans revealed that brain atrophy slowed down in patients receiving LMTX by between 33 and 38 per cent, compared with those taking the placebo.

Tau tangles

“In a study of this size, it is encouraging to see improvements of this magnitude in tests, and reassuring to see supporting brain scan evidence,” says Serge Gauthier of McGill University in Montreal, Canada, who presented the trial results today at the Alzheimer’s Association International Conference in Toronto.

In a field that’s plagued by failures of new drugs in late-stage trials, and where there’s been barely any therapeutic advances over the past decade, I’m excited about the promise of LMTX, says Gauthier.

The trial is the first major test of a drug that targets tau tangles – abnormal protein clumps that accumulate and spread in the brains of people with Alzheimer’s disease, disrupting brain function. Most previous drugs have instead targeted a different protein – beta-amyloid – which also accumulates in the brain, forming plaques that many have believed to be the primary cause of Alzheimer’s symptoms and brain degeneration.

Yet the results from trials for drugs that target beta-amyloid have been consistently disappointing. The success of the LMTX trial suggests that tau tangles might be the main cause of Alzheimer’s symptoms instead.

“In Alzheimer’s, the most likely scenario for successful future treatment is addressing the disease from multiple angles, so having a drug that targets tau is a very hopeful sign,” says Carrillo.

A puzzling result, however, was that LMTX did not seem to have the same effect in those taking the drug in conjunction with other Alzheimer’s medication. Wischik says the most likely explanation is that these other drugs help to clear toxic material out of the brain, so may also clear away LMTX too.

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