Tobias Hartmann: Arresting Alzheimer's
-
<ic:message key='Bild vergrößern' />
- Tobias Hartmann is a dedicated Alzheimer's researcher, and is hoping to find ways to stop the disease. Quelle: Hartmann
15.05.2008 -
Alzheimer's is an insidious disease. The patient inevitably loses their memory, which is followed inevitably by dementia, and then death. But how inevitable is this process really? "I get excited to meet Alzheimer’s patients who could see the progress of the disease halted with our new treatment. This would really be an achievement," says Tobias Hartmann. A few years ago, the biologist revealed how the development of Alzheimer's was related to the lipid metabolism. Today, at the University Hospital of Saarland’s Institute of Neurobiology, he is developing a therapy that he believes could halt the progress of the disease.
Alzheimer's occurs when a specific protein begins to accumulate in the brain. It is now over 100 years since Alois Alzheimer first identified and described the disease. However, it was not until the 1980s when the German researcher Konrad Beyreuther discovered which specific protein blocks the nerve cells. He named the substance "Amyloid Beta". At the time, the scientist assumed that Amyloid Beta was just a waste product, with no other significant role other than obstructing the proper functioning of the brain.
Tobias Hartmann’s team is part of the National Genome Research Network, which has united over a hundred research groups from across Germany to shed some light on the function of human genes. One focus of the work being carried out is neurodegenerative diseases. |
In the 90s, as Hartmann was researching for his doctorate as a member of the working group led by Konrad Beyreuth in Heidelberg, Germany, he made an challenging new observation. The biologist was working with cells that he propagated in culture dishes. Normally, cells are bred in a liquid culture that contains a blood extract from cow embryos, known as foetal calf serum. Hartmann noticed that the cells stopped producing Amyloid Beta if they weren’t given this extract. "This was an observation that probably dozens of doctoral students before me had also made, but nobody seemed to give it a second thought.” For Hartmann, however, this was an explosive discovery, because some substance in the calf serum was clearly encouraging the production of the Alzheimer’s-causing Amyloid Beta.
How cholesterol and Alzheimer’s are related
Hartmann’s scientific curiosity was awakened. Was if the proteins that were bringing the disease about? Hartmann destroyed all the proteins in the serum, but the cells nevertheless continued to produce Amyloid Beta. It was also not a consequence of the salts in the serum. A friend and colleague eventually found the missing piece of the puzzle: the cholesterol fat was stimulating the cells to produce greater quantities of Amyloid Beta. The process could be related to the lipid metabolism. But how?
Cholesterol is a substance that occupies the minds of many medicinal researchers. It is currently assumed that elevated cholesterol levels can lead to heart disease. Drugs exist - the statins - that are able to reduce cholesterol levels. Shortly after his discovery, Hartmann began a limited medical study of Alzheimer's patients, who were administered with high doses of statins over a period of six months. The outcome was that patients were healthier in the early stages of the disease than the patients in the control group. This suggested that statins could also prevent the disease from progressing. But before the new therapy against Alzheimer's could be properly applied, it first had to be tested on a much larger group of patients, and Hartmann initially lacked the funding for a major medical study of this type. The pharmaceutical industry was not interested, as statins were not thought to be big earners: the patent for their application had expired.
Alongside, Hartmann wanted to find out the role that Amyloid Beta plays in fat metabolism. He bred mice, in which he had switched off the gene that was responsible for the material produced by Amyloid Beta.
With this modification, the mice no longer carried the Alzheimer's-causing substance. Hartmann then observed the effect that this had on fat reserves. "I thought: Damn, that's just too good to be true," recalls the scientist. The cholesterol levels were twice as high as usual. "We knew we had made an important discovery, although we weren’t able to classify it exactly. We had found the key to a treasure chest, without any idea what was inside.”
Today, Hartmann knows what is inside the chest: Beta Amyloid is part of a control circuit that steers cholesterol levels (2005, Nature Cell Biology, Vol. 7, Nr. 11, p.1118-23). If there is too much cholesterol, then Amyloid Beta production is stimulated. In turn, Amyloid Beta inhibits an enzyme that is important for cholesterol production. The cholesterol levels decrease. This means that the Alzheimer’s-causing substance is actually not a waste product, but an important part of our metabolism.
| Alzheimer's and Nutrition |
| If Alzheimer's is related to the lipid metabolism, then the progress of the disease could possibly be held back through a course of targeted nutrition. This line of argument is being investigated through the "LIPIDIDIET" project - part of a consortium led by Hartmann - which has been running since late 2007, and which is funded by the European Union with eight million euros. For more information, please go to http://lipididiet.eu/ |
Alzheimer's is a disease that can strike anybody
But Hartmann still retains hope: "In principle, Alzheimer's is amazingly suited for a cure, because it so clearly depends on the concentration of a specific substance, and this concentration need only be slightly reduced. The broad medical study of early-stage Alzheimer's patients, which six years ago was not possible due to a lack of funds, is finally underway. The funding is flowing from support programs, including the German Research Association and the "Innovative Therapies" program from the Federal Ministry of Education and Research (BMBF). If Hartmann’s suspicions are confirmed, then we may soon see the development of a means to stop Alzheimer's in its tracks.
Author: Ragnar Vogt
