Alzheimer’s Disease – Development of a Vaccine against β-Amyloid
Niels Andreasen is Senior Consultant and Head of the Department for Clinical Drug Research at Karolinska University Hospital Huddinge, Stockholm, Sweden. He has conducted more than 100 trials as Primary Investigator and has been National Coordinator in more than 15 studies.
He has a very broad experience with clinical trials on new drugs for dementia diseases, working with most of the major pharmaceutical companies in Phase I – III studies. His centre is currently performing 10 studies. Among others, he has been conducting 7 different vaccination studies and 2 different studies of γ-secretase inhibitors.
Dr. Andreasen has an expertise in Geriatric Medicine, being particularly interested in dementia diseases, especially Alzheimer’s Disease. His basic science research interests include the search of reliable biomarkers for the diagnosis of dementia diseases, with focus on Alzheimer’s Disease. Most of his scientific work has been on biomarkers in the cerebrospinal fluid and he has published more than 120 scientific papers in several peer-reviewed journals. Dr. Andreasen has consulted for several of the major pharmaceutical companies.
During his lecture, Professor Andreasen showed the latest results of his research on a new drug for the treatment of Alzheimer’s disease – it is a vaccine that prevents the aggregation of β-amyloids in the brain. This research can finally bring a light to the millions of patients haunted by this degenerative disease and their families in constant distress.
FRONTAL: The amyloid cascade hypothesis is the most accepted model for the pathogenesis of Alzheimer’s disease (AD). Working in clinical research for new ways to treat this disease, which new targets are now the aim of your research? Is the vaccination the only way to target them or are there other ways?
Niels Andreasen (NA): I think that the amyloid cascade hypothesis is still the most used and it is also the one which allows a better chance for drug development. The vaccine is still in focus. Although some drugs as Bapineuzumab have been aborted due to their side effects and lack of efficacy, there is still hope for some other drugs to reach our pharmacies during the next 3 to 4 years, especially for Solanezumab. A new study on very early AD has started on this drug. We have to look for new targets, because all researches are focused on the vaccine, γ-secretase inhibitors and BACE inhibitors. All but one γ-secretase inhibitor were aborted due to the high number of reported side effects. Another option is the BACE inhibitors. Unfortunately, Lilly’s (pharmaceutical corporation) BACE inhibitor was also aborted.
F: So far, symptom-improving drugs are the only weapons we have against AD, producing only modest results. Therefore, it looks like prevention would be a successful route in this area. However, when disease occurs curing is the next best thing. Being aware that your research is not focused on prevention, is there any indication that the same weapons could be used to delay disease progression?
NA: I am sure that our research will help in the treatment. Primary prevention will be very tricky to do, because it takes a careful case-control study that can take up to 20 years. There are many international studies regarding secondary prevention, such as FINGER in Finland, the Pre-DIVA study in the Netherlands and the MAPT in France. In Karolinska (Stockholm) we use the cerebrospinal fluid in order to identify the amyloid presence as well as many vascular risk factors, such as: blood pressure, cholesterol and obesity. There is interesting information about this subject, such as the Karelian study in Finland, which successfully prevented hearth infarctions by controlling blood pressure and cholesterol. It will be interesting to see if the same treatment that prevented myocardial infarction can also prevent AD. We do not know it but we are looking forward to finding it.
F: With the theoretical arrival of a way to prevent the disease another question arises: How to sort out the adequate candidates for prevention? How would you propose for this “selection” to be done?”
NA: That is a very tricky subject because it is more or less an ethical question. I used to compare it to a person that takes a flight in a plane that is about to crash. If you could exit the plane it would be great to know that it would crash, but if you could not exit it would not be nice to know that you are flying in a plane that is going to inevitably crash in 1,5 years. The same happens to Alzheimer’s. With the tools we have today we can diagnose the disease at least 10 years before its onset, but then the problem arises: Is it ethical to tell to a healthy individual that he/she will develop Alzheimer’s in 10 years, knowing that he/she is not a candidate for the new drugs?
F: Despite prevention being a desirable goal – once it avoids the development of the disease – it is not a possibility sometimes. As far as AD is concerned, how far are we from its effective pharmacological prophylaxis?
NA: It is almost a Nobel question. We do not know if Solanezumab, one of the vaccines, is successful, and it seems like it will be. But we need to perform the phase 3 study, which started just a month ago in the USA, and started this month in several European countries, including Sweden. I can say that in 5 years from now we will have a good disease modifying treatment.
F: Considering the current aging of the so-called developed world, dementia is escalating the charts to become one of the most prevalent morbidity causes worldwide. This also turns this issue into a political one. How do you feel that politicians, in general, face this problem and how does that influence, for instance, the attribution of public research grants?
NA: In 1999 there was a paper from the UK that showed that half of the total budget for healthcare actually goes for Alzheimer disease, and it is associated with its morbidities. This was more than the combined expense for Cancer and Cardiovascular Diseases. Ironically, if you looked at the research budget, the Alzheimer’s budget was only 0,5%, CV diseases had 1,4% and Cancer 11,6%. This is probably because cancer patients have an intact cognitive function and therefore they “shout” if they do not get their medication, whether the Alzheimer’s patients cannot demand their rights. However, there is a growing political awareness about this health problem. You have the example of the ICAD Conference in Paris, 2 years ago, where President Sarkozy presented an enormous budget destined to works on treatment of AD. Another important moment occurred half year ago, when President Obama revealed that the investigation on AD would be a major national goal for the next ten years. I am quite positive about it. The other thing is that, with the Internet, people are getting more aware about this disease. The amount of information today is much bigger than 4 years ago. That means that the demands from the patients and from their relatives are increasing.
Interviewers: Marta Batista, Sara Silva
Writers: Santiago Rodrigues Manica