Fighting Alzheimer's

DW: How great is the problem facing us today with regard to neurodegenerative diseases?

In 2050, we're going to have over 3.5 million people with Alzheimer's disease alone if no ways are found to treat this. Worldwide - and this is surprising - the largest increase will be in third-world countries, because the difference in the age profile is going to be steeper.

For us, the costs in health care are going to be astronomical, and what's more, there are no treatments.

How important is the partnership signed with the University of Wisconsin today?

In Wisconsin they're very much ahead with the academic development of finding new ways to develop drugs and we're very strong on fundamental research to identify new paths and targets that can be explored with regard to neurodegenerative diseases.

I think the key issue is not so much whether we can develop new medicines, but how long it will take until they can be administered. The policy of the DZNE (German Center for Neurodegenerative Diseases is to establish partnerships like the one we've just signed, but also with industry, where we share the burden of developing medicines.

Any specific research fields that are promising?

Inflammation is certainly one. It is becoming more and more obvious that a number of [pre-existent Alzheimer's] cases are worsened by concomitant inflammatory events. A simple flu, or tooth infection, or systemic infections, for example. We are developing medicines which we hope will be very effective in reducing the initial effects of infections on the brain, and therefore reducing the risk of Alzheimer's disease.

Other research areas that are becoming very important are vascular disease and the environmental influence on brain network activity. That is how the brain network reacts to injuries. We're not going to have damage in a single neuron, or a single group of cells, but rather in the network activity. So we will discover that, paradoxically, in individuals where there isn't any major damage to the brain, there is major damage to how the neurons work together as a network. [They are] more likely to develop dementia than in individuals who might have major neuron loss, but can still retain network activity.

How does stem cell research fit in to all this?

With stem cells, you can rebuild - in vitro - part of the functions that are taking place in the brain, which allows us to investigate mechanisms of disease and identify new targets for medication. You can also use stem cells for screenings. So instead of screening animal cells, you can screen human cells, which have been reprogrammed as neurons.

But using stem cells directly in therapy is very much in its infancy. It was tested years ago with Parkinson's disease. In fact, my group was involved in one of the early studies, together with Swedish colleagues. It worked in many cases. But with regard to Alzheimer's, there is no evidence that stem cells may be useful in this context.

What are the main scientific stumbling blocks in tackling neurodegenerative diseases right now?

One is the lack of appropriate models of disease. We can model certain features, but not the disease as a whole. We are developing animal models, which are coming closer to what the disease is in humans, but they still have limitations.

The second obstacle is more conceptual. Over the past thirty years, the research field has been focused on making therapeutics on very specific paths that definitely are involved in the disease, but they may not be the only one that are important for the disease. It's very difficult to target, because the disease may start 20 years before the first symptoms arise. So these therapies are often too late. The question is and some trials are trying to address this: Can we give these medicines or antibodies to patients who have not yet developed the disease, but who, based on their genetics, for example, will develop it? And then we can find out whether there is an improvement? There is no evidence at the moment that such medication administered to patients who already have the disease improves their lot.

What we need is early detection, early diagnosis and early therapy. But if we could delay the progress of the disease by another ten years or even the onset we would have solved a tremendous cost and social problem even if we couldn't prevent the person from succumbing to it.

DZNE's research is focused on prevention and treatment. How confident are you that one day you'll be able to actually cure neurodegenerative diseases such as Alzheimer's?

Personally, when I took this job, I said that I hope that by the time I retire, we will at least have found something that will at least ameliorate the life Alzheimer's patients. This is not necessarily a cure or prevention, but that the quality of life will improve. The target by 2025 would be to give two more years of good quality life to somebody who will develop Alzheimer's disease. I'm optimistic. I think we will have symptomatic therapies in place by then, and be will able to delay the onset of the disease with early diagnosis.

Professor Pierluigi Nicotera is the Scientific Director of the German Center for Neurodegenerative Diseases (DZNE) in Bonn.