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Drug Research for the Treatment of Alzheimer’s Disease

Today, more than 1.2 million people in Germany suffer from Alzheimer’s disease; globally this figure is estimated to be more than 24 million. As the risk of developing the disease increases sharply in old age, it is expected that this number will rise to more than 40 million by 2030. As the disease progresses, massive nerve cell damage and death in the brain cause a severe decline of cognitive abilities, particularly memory. The expected increase in case numbers, the suffering of patients and their families, and the enormous economic costs make Alzheimer’s one of the most pressing challenges health research is facing.

Aggregates of the amyloid-beta (Aβ) peptide are thought to cause the disease. Single Aβ molecules or “monomers” are initially harmless, but they can bind to each other to form small, soluble aggregates (oligomers) large fibrils and plaques, that are eventually deposited between nerve cells in the brain. While research has long focussed on reducing the plaques, today a growing body of evidence points to the oligomers as the main culprits in pathology, with a highly toxic effect on neurons.

Schematische DarstellungIn the brain, the A? peptide is cut out of a larger protein molecule by enzymes. As Alzheimer’s disease progresses, single A? monomers combine to form oligormers and fibrils.
Copyright: Tricklabor

At Forschungszentrum Jülich, a team of researchers headed by Prof. Dieter Willbold has therefore developed a novel drug candidate that targets these oligomers and renders them harmless. In vitro studies showed that when the peptide was added, the oligomers disappeared. The effect of the candidate drug has also been verified in animal models: in tests with "Alzheimer’s mice", treatment with the substance improved memory and learning abilities and also led to a decrease in plaque deposits in brain tissue of the mice. In order to verify the suitability of the drug candidate for use in humans, a large-scale project funded with € 2 million provided from the Helmholtz Validation Fund started in September 2014.

"First of all, the safety and tolerability of the candidate drug must be determined in further preclinical tests on animal models and then in clinical trials with healthy human volunteers," says Prof. Willbold. Only after the clinical phase 1 trial has been successfully completed in about two will the first studies on patients with Alzheimer’s be possible.

Further Information:

Press release: Launch of Alzheimer’s project (in German; 4 Sept. 2014)