Living with Dementia February 2009

Here, we take a look at how trials to develop new drugs for Alzheimer's disease fared in 2008.

Anyone whose life has been affected by Alzheimer's disease understands the desperate need for new drug treatments. Developing and testing a drug takes 20 years on average from the scientific discovery to the treatment actually being available to people with dementia. This article reviews current progress in the search for treatments to significantly slow or halt Alzheimer's disease.

Showing promise
Dimebon was developed in Russia in the 1980s as an antihistamine and has been used by allergy sufferers for over 25 years. In July 2008 the medical journal The Lancet reported that a trial had shown Dimebon to be twice as effective as current cholinesterase inhibitors, such as Aricept, when used as a treatment for Alzheimer's disease. A major pharmaceutical company has now bought the rights to Dimebon and phase III trials of the drug are now underway in the US.

Conference reviews
July 2008 was a packed month for news on Alzheimer's treatments as researchers from all over the world presented papers at the International Conference on Alzheimer's Disease (ICAD) in Chicago. Rember and Flurizan both hit the headlines. While Rember was hailed in the press as a great new hope, Flurizan was unfortunately declared a failure.

At the ICAD conference researchers revealed that in trials Rember (a form of methylene blue) had slowed the progression of Alzheimer's disease by up to 81 per cent. Although the results generated much excitement and hope, they have not yet been properly peer reviewed.

The Society's Director of Research, Professor Clive Ballard says,

'The results appear to be promising but we are not there yet. Larger scale trials are now needed to confirm the safety of this drug and establish the benefits it can offer.'

Flurizan (its trade name is tareflurbil) is a drug that had made it to phase III trials. However, results showed few significant improvements for people with Alzheimer's who had taken it. Professor Ballard says,

'This is an important lesson in understanding that many drugs which appear promising in early clinical trials will not necessarily be effective when examined more rigorously.'

A drug known as PBT2 fits neatly into the 'appears promising' category. In September, results of a phase II trial published in The Lancet Neurology journal showed that it appeared to reduce levels of amyloid (a protein found in the brains of people with Alzheimer's disease) and have positive effects on the symptoms of Alzheimer's disease. PBT2 works by binding itself to copper and zinc in the brain with the effect of reducing the build-up of amyloid.

Most promising treatment
The treatment known as bapineuzumab is probably the most promising treatment currently in development. If results from ongoing trials are positive it is expected to become available in 2011.

Bapineuzumab is a passive vaccine. Trials of an active vaccine were halted in 2002 when a small number of patients developed serious side effects. Bapineuzumab is passive because it supplies anti-amyloid antibodies directly to the immune system rather than stimulating the immune system to produce its own. It is hoped that this lack of stimulation will mean that bapineuzumab will prove to be a more stable treatment.

Results from phase II trials reported at the ICAD and Springfield conferences last year were mixed, but there is evidence that bapineuzumab can produce significant benefits for some people with Alzheimer's disease. It is currently being tested in phase III trials, including centres in the UK.

Making the best use of current drugs
The Society and the Medical Research Council are jointly funding a clinical trial to investigate the best use of current medications for people with moderate to severe Alzheimer's disease. This trial is known as the DOMINO trial and will assess whether donepezil alone or donepezil combined with mementine can give significant benefits when prescribed for six months longer than current NICE guidance recommends.

Participating in clinical trials
The DOMINO trial and the bapinueuzumab trials are still recruiting participants. If you want to find out more about the DOMINO trial, you can call 020 7848 0024, email mary.griffin@iop.kcl.ac.uk or write to PO70, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF. You can also find more details at
www.neuroscience.iop.kcl.ac.uk/domino/

People in London can find out more about the bapineuzumab trials from the clinical trials team at the Wolfson Centre at King's College London. You can call 020 7848 8071 or email Katja.Kossakowski@kcl.ac.uk

Future
The Society is working in partnership to develop a comprehensive and accessible list of UK-based clinical trials to make it easier for people to find out about taking part in ongoing trials. Further information will be included in this magazine as developments take place.

Read our factsheet Volunteering for research into dementia (409),

Read our factsheet on dementia: drugs used to relieve depression and behavioural symptoms

Find out more in our research section