Tangles in the brain THOMAS DEERINCK, NCMIR/SCIENCE PHOTO LIBRARY

A drug that has failed in a large clinical trial may still show promise for halting the progression of Alzheimer’s disease.

The drug, called LMTX, was tested 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.

While the drug did not prove successful for treating people who are already taking other Alzheimer’s medication, it did seem to have an effect on a smaller number of people who took only LMTX.


“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. Of these, 15 per cent received LMTX alone, while the others either took it in conjunction with other treatments or 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,” said Serge Gauthier of McGill University in Montreal, Canada, who presented the trial results today at the Alzheimer’s Association International Conference in Toronto.

Wischik says that the most likely explanation for why LMTX seems to only work when taken without other drugs is that other Alzheimer’s treatments help to clear toxic material out of the brain, and may also clear away LMTX too.

The trial was 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. If further tests confirm that taking LMTX on its own really does slow the progression of the disease, this would suggest that tau tangles might be the main cause of Alzheimer’s symptoms instead.

The facts that LMTX failed as a treatment to be used in combination with other medication, and that the group who took the drug alone constituted 15 per cent of the total trial participants, have been clarified.