Disappointment and promise in tau drug trial

From the Autumn 2016 edition of Care and cure magazine, the first drug to target tau tangles fails in clinical trial but produces intriguing results.

Several neurodegenerative diseases involve the production of toxic clumps of proteins that cause damage to nerves. In Alzheimer's disease, the protein culprits are amyloid, which forms large build-ups called plaques, and tau, which forms harmful tangles inside brain cells.

For a long time, amyloid has been the main target of drugs designed to treat Alzheimer's disease. However, several of these drugs have failed once they are tested in clinical trials. Focus has shifted onto targeting tau in the hope that this will be more successful. This summer, the results of the first clinical trial to target tau were announced.

The trial was for a drug called LMTX and involved almost 900 people with mild to moderate Alzheimer's. The participants took either LMTX or a placebo pill twice daily for 15 months. Disappointingly, the overall results were negative - the drug failed to improve memory and thinking performance or to affect brain shrinkage compared to the placebo over the course of the trial.

However, when the researchers examined the findings in more detail, there was a silver lining. A small subset of people on the trial - those who were not taking any other Alzheimer's medications - did show positive results.

'While it's disappointing to see another large clinical trial for Alzheimer's disease fail to meet its goal, there appears to have been some striking improvements for the subset of people who took the drug on its own,' said Dr Doug Brown, Director of Research and Development at Alzheimer's Society.

For the people who took LMTX alone, there was a reduction in brain shrinkage by 30-40 per cent. This group also saw significant improvements in memory and thinking tests, and in their ability to get on with day-to-day tasks such as dressing, cooking and using public transport.

'There are still lots of questions to answer before we know how promising this new treatment could be, such as why it doesn't appear to work in those who are already taking other medications for Alzheimer's disease,' said Dr Brown.

The number of people who took the drug on its own was small -only 82 people - and so these results will need to be verified in a larger study before it could even be considered for approval as a new treatment. A second study of LMTX in people with mild Alzheimer's disease is due to report its results in December and we will keep you updated with any news.