One of the things that makes Alzheimer’s disease so hard to treat is that scientists still don’t understand the basic biology behind what’s driving the disease. We spoke to Dr. Bart de Strooper, a molecular biologist and the Director of Dementia Research Institute at University College London about his efforts to unlock the pathways that lead to the breakdown of nerve cells and why he thinks beta amyloid and tau are still the best targets for drug trials, despite repeated failures.
- Patients with markers of Alzheimer’s like tau and beta amyloid are able to function normally for 20 or 30 years. Finding a cure lies in understanding what happens before dementia sets in
- Scientists want to attack Alzheimer’s in the same way the scientic community has pursued a cure for cancer
- We hope to have a drug that postpones the disease in 5 to 10 years
Being Patient: What are you trying to uncover in your research?
Bart de Strooper: One of the questions which fascinates me is that you have these biochemical changes [the build up of tau and beta amyloid] in patients but these patients still have normal functioning. Then 20, 30 years later, they start to become demented. The goal for me is to understand how the normal brain is able to cope with these disease-causing agents for 10, 15, 20 years. We need to understand those mechanisms. My belief is that by understanding the mechanisms, there will be new drug targets and new ways to treat or to prevent a disease.
Being Patient: Some scientists believe that research needs to be expanded beyond examining tau and amyloid. Do you agree?
Bart de Strooper: We need to become much bigger than we are in our limits. The brain is such a complex organ and the disease is a multi-system dysfunctioning, so I think we need to take example from the cancer field, which covers thousands of research fields. That’s a challenge. In the last 10, 15 years we have tried to come up with very precise questions and address them. I think that will continue but we will do it over many, many more things at once. So [at the Dementia Research Institute] one of the groups will investigate how the biochemistry changes the synapse function and another one will try to understand how the microglia intermingle with the biochemical phase to affect the synapse function.
Being Patient: The focus of most clinical trials is still on drugs that attack beta amyloid and tau. Do you think this is the right approach?
Bart de Strooper: These are the only things which we really understand quite well. I think these are golden opportunities to do something about the disease but what the clinical trials have shown is, first of all, it is very difficult to hit these targets. The second thing that we’ve learned is that there are tremendous side effects if you want to hit beta amyloid and treat that. We simply do not understand enough about the other mechanisms, like inflammation, to make them really good drug targets. Everybody is talking about inflammation but nobody’s telling me what part of the inflammation we have to inactivate or activate or when you have to interfere.
Being Patient: With new centers like yours being founded, where do you think the research will be in five years time?
Bart de Strooper: My hope is that we are accelerating much more than we think. There is much more money in the field and people are starting to ask much deeper questions while at the same time we have better tools and methods. The war on cancer started under Nixon. People forget that, but it was in the late ’60s. The goal was to have a drug in five or ten years. It has taken 40 years to be where we are but the landscape around cancer changed completely. I think dementia will be the same. We will not be able to cure everything, but the perspective will be very different. Now we have to say, “Yeah, you have that. We cannot do anything for you.” I think in five, eight, ten years, we will have several drugs. One of them will be amyloid therapy and we’ll say, “Look, for you, it will postpone your disease.”