Malaria drugs offer CJD hope

Malaria drugs offer CJD hope

August 11, 2001 The Herald (Glasgow) by Alan Macdermid

DRUGS commonly used for years to combat malaria and mental illness may offer an effective treatment for Creutzfeldt-Jakob disease, scientists said yesterday.

So far more than 100 people in the UK have contracted the variant of CJD associated with mad cow disease, and there are fears that thousands could turn out to be affected.

It is one of a series of diseases attributed to the effect of "rogue" prion proteins which get into the brain and change normal proteins into the same mis -folded pattern. They are invariably lethal, characterised by progressive neurological dysfunction.

Now researchers at the University of California, San Francisco, led by Professor Stan Prusiner, the scientist who first described the role of prions in these diseases, have conducted laboratory experiments which indicate that quinacrine and chlorpromazine, two drugs with certain common structural characteristics, appear to inhibit the conversion of normal prion proteins into disease-causing aberrant ones.

Both drugs, which have been used in humans for many years - quinacrine as antimalarial and chlorpromazine as an antipsychotic - are known to cross the blood-brain barrier.

Writing in the Proceeds of the National Academy of Sciences, Professor Prusiner and his colleagues conclude that tricyclic compounds like these, with distinctive side-chain structures at particular positions within the molecule, constitute a new class of antiprion agents.

The compounds have not been tested for this purpose in animals, so it is not certain whether their effect on protein folding has any direct therapeutic relevance to animal or human forms of prion diseases.

However, they are "immediate candidates" which could be used in clinical trials on people suffering from CJD or other prion diseases.

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