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Therapy For Alzheimer's In Sight?

September 20, 2004
University Of Bonn
Immunoglobulins which are already being used to treat multiple sclerosis may also be able to help patients with Alzheimer's. This, at least, is the finding of a pilot study on five patients at the University of Bonn.

Immunoglobulins which are already being used to treat multiple sclerosis may also be able to help patients with Alzheimer's. This, at least, is the finding of a pilot study on five patients at the University of Bonn. The results are set out in the forthcoming edition of the Journal of Neurology, Neurosurgery and Psychiatry (vol. 75, pp. 1472-1474), which also devotes its editorial to this discovery.

Immunoglobulins contain, among other things, anti-bodies against a protein which is the 'main suspect' thought to trigger off Alzheimer's. After six months of immuno-globulin doses the concentration of this protein in the patients' cerebrospinal fluid was reduced by one third. The patients' cognitive abilities improved slightly.

However, the medical team involved emphasise that their findings are still very tentative. They are now planning a large-scale double-blind clinical trial with about sixty patients so as to further confirm the positive effect of the immunoglobulins.

The cerebral cortex of Alzheimer's patients regularly contains large protein aggregates, what are known as Alzheimer's glands. They predominantly consist of beta-amyloid peptide, a small protein. This peptide collects in the brain of Alzheimer's patients and forms protein deposits which can damage and even destroy the sensitive nerve cells.

A promising approach in combating the disease seems to be the treatment with anti-bodies which are specifically effective against beta-amyloid. Thus, in animal experiments the injection of beta-amyloid anti-bodies led to a reduction in the protein deposits and an improvement in the behavioural deficits in these animals. Another study recently showed that immunising was not only able to reduce amyloid plaques, it also prevented the formation of the abnormal tau protein.

Recently the team led by the Bonn lecturer Dr. Richard Dodel was able to show that every person's blood contains anti-bodies against beta-amyloid, but that the concentra-tion in Alzheimer's patients is markedly lower. Their findings have been confirmed by two US teams. 'There are already anti-body blood preparations which are used for particular diseases of the nervous system such as multiple sclerosis, which are known as immunoglobulins,' Dr. Dodel explains. 'We have now investigated whether these preparations contain anti-bodies against beta-amyloid and if these can be used to fight Alzheimer's.' His team did in fact find anti-bodies in one type of immunoglobulin medication which are very effective specifically against beta-amyloid. In a pilot study carried out on five Alzheimer's patients the team then studied the effect of the immunoglobulins on the progress of the disease. This involved giving the patients an immunoglobulin injection intravenously every four weeks throughout the six-month study. Before beginning and on completing the therapy the researchers determined the beta-amyloid content in the blood and the CSF fluid – the latter being the liquid which is present in the brain and spinal cord. 'On average the beta-amyloid concentra-tion in the fluid decreased in the course of the study by over 30 per cent, while the concentration in the blood rose 2.3 times,' Dr. Dodel says. 'The immunoglobulins therefore seem to have the effect of flushing out the beta-amyloid from the brain' – how exactly this occurs is as yet unclear.

At the same time the team carried out various tests which enabled them to check the cerebral performance of dementia patients. After six months four of the five patients did slightly better than before in what is known as the ADAS-cog test (Alzheimer's Disease Assessment Scale, cognitive subscale). In the MMSE (Mini-Mental State Examination) test three patients improved. 'What is even more remarkable is that none of our test persons deteriorated,' Dr. Dodel explains. 'Without treatment Alzheimer's patients on average score seven to eleven points worse in the ADAS-cog test one year later, and even patients on medication score four to six points worse. In our study they improved on average by 3.7 points.'

However, the sample was far too small to be able to draw firm conclusions about the effectiveness of immunoglobulin therapy, since the substance was not tested in comparison with a placebo. 'We only carried out a pilot study,' Dr. Dodel emphasises; 'in order to confirm our findings we definitely need to carry out a double-blind trial with larger patient numbers.'

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