Expert reaction to drug that is reported to restore memory loss and prolong life in mice as published in the Journal of Clinical Investigation*

Posted by pt91 at Jan 04, 2017 12:40 PM |
Science Media Centre Roundup

Version 3: *NEW COMMENT* Dr David Reynolds, Chief Scientific Officer, Alzheimer’s Research UK, said:

“These kinds of detailed early studies in mice are important for exploring potential drug targets to follow up in the search for new treatments for diseases like Alzheimer’s. Efforts to target this particular protein have been ongoing for several years but have hit hurdles around safety that could limit their use in people. One encouraging aspect of this study is that the chemicals were able to extend the lives of mice, suggesting that it’s an area of drug discovery where efforts should be boosted. The long wait for new Alzheimer’s treatments illustrates the challenge in developing new drugs against the disease and any potential new approach would have to be safe and effective in people.

“It’s almost 15 years since the last drug for Alzheimer’s became available and it’s promising to see new avenues being explored. To have the best chance of ending the long wait for new treatments, researchers will need to follow as many leads as possible, creating a diverse pipeline of potential targets for further development. Not all of these new drugs will be successful, but it only takes one success to change the lives of people with dementia in the future.”

Dr James Pickett, Head of Research at Alzheimer’s Society said:

“Current drugs for Alzheimer’s disease work by boosting levels of an important chemical messenger in the brain. These drugs can help relieve symptoms of Alzheimer’s disease in some people, but can also cause unpleasant side effects like loss of appetite, nausea, vomiting and diarrhoea. This thorough study describes a new drug that has a more selective effect. It still boosts levels of the chemical messenger, but because the drug is more precise, it may not cause as many side effects.

“The principle is that with fewer side effects a higher dose can be given, and if it works in practice that could mean a more effective treatment. This study shows that the drug is hitting its target in mice, but it’s uncertain if it would provide any real benefits for people with Alzheimer’s disease.

“There is currently no cure for dementia, and there have been no new treatments for well over a decade. While there are still a number of hurdles for this drug to overcome, it’s positive to see new approaches being explored. Now dementia is the biggest killer in England and Wales, the race is on to find more effective treatments.”

Prof John Hardy, Professor of Neuroscience, UCL, said:

“This study reports an apparent small improvement in behaviour and survival in prion infected mice when treated with a novel cholinergic drug.  Any improvement in outcome and survival in any dementia would be welcome.  However, the effects are modest (perhaps an extra week of survival) and the model is questionable, especially in terms of its relevance to Alzheimer’s disease.”

Dr Tara Spires-Jones, Interim Director, Centre for Cognitive and Neural Systems, University of Edinburgh, said:

“This study shows that treatment with a new type of drug improves brain function in a mouse model of prion disease.  The results are robust in this prion disease model; however, while scientifically interesting, these results are very far from demonstrating that this type of drug will be beneficial in Alzheimer’s disease.   This treatment affects one kind of receptor molecule in the brain, called cholinergic receptors.  The "cholinergic hypothesis" which proposed that loss of cholinergic neurons is the main force driving Alzheimer's disease has been soundly disproven, and it is clear that treatments targeting only cholinergic loss will not be disease modifying. Current treatments for Alzheimer's that affect this cholinergic system are not very effective. While this new type of drug may be better, so much more goes wrong in the brain than changes in cholinergic signalling that it is unlikely to cause dramatic improvements in people living with Alzheimer's disease. Furthermore, this is a study of a prion disease model, and there is a long way to go to demonstrate that the mechanisms of brain degeneration in this prion model are the same as those causing human Alzheimer's disease.”

* ‘M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss’ by Bradley et al. will be published in the Journal of Clinical Investigation at 21:00 UK time on Monday 19th December, which is also when the embargo will lift.

Declared interests

Dr Reynolds: “Nothing to declare.”

Dr Pickett: “Nothing to declare.”

Prof Hardy: “I consult for Eisai.”

Dr Spires-Jones: “I am on the Grant Review Board for Alzheimer’s Research UK and collaborate with pharmaceutical company Cognition Therapeutics.”

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