New dementia drugs in the pipeline

25 March 2011

This memory test requires the subject to quickly and correctly describe all the symbols, row by row:

There is currently no cure for Alzheimer’s disease. However, a number of possible drugs are being tested and in the future middle-aged people could be screened for early signs of the disease.

This is what Professor Lennart Minthon of Lund University believes; his research group studies the origins and treatment of dementia.

One problem with Alzheimer’s disease is that the underlying changes in the brain occur so early. It is now believed that they begin 20 years before the patient notices the first signs of memory loss. This is one reason why today’s drugs cannot cure the disease: by the time a diagnosis is made the changes have already progressed too far.

“Once new, more effective medicines have been developed, we will probably want to test all middle-aged people”, says Lennart Minthon.

His idea is something along the same lines as mammograms, which are performed on healthy individuals to discover early symptoms of a serious disease. Screening for dementia would be expensive, but should be worth it.

“Dementia costs society SEK 51 billion a year. Dementia patients can live for many years with the disease and need a lot of supervision”, says Lennart Minthon, who has calculated that the SEK 51 billion corresponds to over SEK 1 000 a second.

His research group is linked to Sweden’s largest memory clinic, which is based at the Neuropsychiatry Clinic in Segevång in Malmö. Health care staff and researchers work side by side to examine the patients with poor memory.

Some 1 200 patients a year visit the memory clinic. Experience shows that around half of those who seek medical treatment for minor memory problems will deteriorate over time, while the other half will remain at the level of ‘mild forgetfulness’.

The researchers take samples of spinal fluid and scans of the brain from patients with dementia using PET technology. The examinations provide information about the state of the brain and about how much hope there is for treatment. It is often possible to treat Alzheimer’s disease, even if it cannot be cured.

If effective Alzheimer’s drugs are developed, it will be important to identify the patients as early as possible, says Lennart Minthon.“Thirty per cent of patients improve slightly with medication. Sixty per cent become stabilised at their current level, or only deteriorate slowly. Unfortunately, the final ten per cent of patients do not respond to medication at all”, says Lennart Minthon.

There are a number of changes in the brain that are behind Alzheimer’s disease. The cells’ ‘refuse collection’ system goes wrong, causing bundles of dead cells to build up in the brain. A certain protein also changes so that the transport system in the cells becomes clogged and the synapses (nerve cells’ points of contact) are also damaged.

The Malmö group participates in a number of international studies targeting different parts of this disease process. Some drugs are intended to dissolve the accumulations of dead cells in the brain, while others are to prevent damage to the cells’ inner transport system.

New drugs not only have to be tested to see if they work; it is also important to decide how and how often they should be administered, points out doctor Henrik Östlund.The studies are about more than seeing whether the drugs work at all. We also need to know how many doses to give, how often and whether the drug should be given intravenously or injected like a flu vaccine”, explains Dr Henrik Östlund.

Two of the possible treatments are well on the way to becoming finished drugs. Results of trials will soon be available, enabling researchers to see whether the patients who received the drug did better than those who received a placebo. Huge profits await the companies that can develop effective Alzheimer’s medicines, so there is a lot of interest.

Sebastian Palmqvist studies memory tests. Which tests work best and how can the maximum information be extracted from the results?However, before a patient can be treated, a proper diagnosis must be made. Doctoral student Sebastian Palmqvist has gone through a large number of memory tests to sift out those that provide the most accurate diagnosis. The tests need to distinguish the patients with dementia from those whose memory problems have other causes, such as depression, metabolic problems, long-term stress or incorrect medication. The tests should preferably also be able to distinguish between different types of dementia, because besides Alzheimer’s there is also dementia with Lewy bodies and other forms of the disease.

Oskar Hansson searches for biomarkers that show which healthy individuals may later suffer from Alzheimer’s.It is also important to identify future Alzheimer’s patients as early as possible. Doctor and researcher Oskar Hansson has found two risk markers – substances in the spinal fluid of persons who go on to develop Alzheimer’s. He is now continuing his research with a study of 200 healthy individuals over the age of 60.

“We will perform a range of tests and follow the subjects over five years. Statistically, around 20 of them should experience memory loss during that time. Then it will be interesting to see if they had any abnormal results in the early tests”, he explains.

- Ingela Björck