Research for Practical Applications Paving the way for drugs for Alzheimer’s
Computer simulations show two different perspectives of how the D3 peptide binds to the ß-amyloid molecules – shown here as yellow-green strips.
substances that have been clinically tested so far.” Most of them target the chain-like beta amyloid molecule comprising around 40 amino acids, the building blocks of proteins. The beta amyloid molecule can form deposits known as plaques that are characteristic of Alzheimer’s disease and were found in the brains of deceased persons who had been affected by the disease. Some of the candidate drugs that failed
the test were supposed to block the enzymes required for the production of the beta amyloid molecule, for example. “Our approach, in contrast, is not to take action against the beta amyloid molecule, but to stabilize it instead. This is how we want to prevent it from being converted into larger aggregates or plaques,” says Willbold. In their search for substances that act in this manner, they discovered the D3 peptide and a number of its derivatives. These substances contain amino acids that are structured like a mirror image of the amino acids in natural proteins. The advantage of the artificial mirror images: they are not attacked by degradation proteins in the body and are therefore particularly stable. The approach of the Jülich scientists has already proven to be effective in tests on cell cultures and on mice that have mutated genes for a human beta amyloid precursor protein. In these Alzheimer’s model mice, D3 has a positive effect on mental faculties. For example, the animals are better able to remember how to get to the platform in a water pool where they can take a rest.
A team headed by Prof. Dieter Willbold and Dr. Susanne Aileen Funke have developed a potential drug for Alzheimer’s dementia, which will now be tested in initial clinical trials.
Annual Report 2012 | Forschungszentrum Jülich
67
Using knowledge
Despite intensive worldwide research efforts, a drug that is able to alleviate or even cure Alzheimer’s has not yet been found. According to estimates, the number of people currently affected by this form of dementia in Germany alone is around one million. Although promising substances were discovered in the past, they were either found to be ineffective in clinical trials or their side effects were too strong. Prof. Dieter Willbold, director at Jülich’s Institute for Complex Systems (ICS) is confident that his team has found a candidate that will fare better as an active substance. This potential drug will be tested in phase-1 clinical trials during the next two years. In this phase, doctors administer the substance to healthy individuals to find out how well they are tolerate it and how it is transformed by metabolism. The Helmholtz Association is funding the phase-1 trials from its Validation Fund. Willbold believes to have good reason for his optimism: “The mode of action of our D3 peptide derivatives is completely different than that of other