Risposta di Bart De Strooper alle affermazioni di Francesca Pistollato in relazione al morbo di Alzheimer

This is typical example of linking two items that have no direct relationship to make a false claim and to force some political agenda. It is a shame that a scientist makes such correlative arguments in public.

It is a false argument to propose that we have no drugs because the animal models are bad. You could as well say that all the cell biology or all the genetics or all the other science done in this field is bad because it did not deliver yet a successful medicine.
And I strongly disagree with the argument that research in our field has not been successful. We have made enormous progress in the field of Alzheimer’s Disease and other neurodegenerative disorders. Twenty years ago we hardly believed that it was a disease, now we have genes, mechanisms, models, drug targets and the first trials. However the field remains very much underpowered and underinvested. E.g. there are about 43 million people with cancer world wide and 46 million with dementia. It is difficult to estimate how much money is invested in the two areas of disease, but you can go to pubmed to see how much science is done in the two areas. It is a shock to realize that more than 3.800.000 papers on cancer and only about 200.000 on dementia have been published. The main reason that we have no good drugs for AD as yet is simply that we do not know enough about the disease mechanisms at this moment.

The other problem with many clinical trials is that the concept behind them is wrong. They were designed to treat the amyloid in brain, but are tested for effects on dementia symptoms. The link between amyloid and dementia is complicated as it takes twenty years to go from the first amyloid deposits to the clinical phenotype of dementia. It is naïve to belief that after twenty years of disease process everything can easily be corrected. Amyloid treatment needs to be done before neurons and circuitry in the brain becomes irreversibly damaged. The industry needs to think about better trials in earlier phases of the disease.

With regard to your specific question. It is very misleading to say that the animal models of Alzheimer Disease are not useful. About everything which is now found out in clinical trials was predicted in the animal models. The experiments predicted that one should act in a preventive way in the animal models The side effects of gamma-secretase inhibitors were predicted in 1999, the side effects for the BACE1 trials were predicted by many scientists years ago and we warned the industry to be careful. etc etc. Most recently the inflammation in Ad has been first unravelled in mouse models for the disease and is now leading to observations in human. I do not know why people claim that the animal experiments are not useful. They have helped us to understand the disease, they have provided first proof of concept, and they have warned us what could go wrong in human. It is simply unfair to ignore that.

Where I agree is that it is very difficult to model completely Alzheimer’s Disease in animals. We can only generate partial models in mouse because mouse brain and human brain are different. But we still, as explained, can learn a lot and I prefer to start with experiments in mice than in humans.

It is also a false claim that in vitro models can replace all animal work. Brain organoids or other alternatives can NOT replace animal models at this moment as they do not provide a sufficient physiological relevant context to study for instance side effects of drugs or the effect on brain circuitry. As far as I can see it will take at least another ten years before the in vitro alternatives to study human disease will be sufficiently operational to provide trust worthy predictions. In the mean time we will also have to compare findings in brain organoids and animals to know whether we move in the right direction.

There are little areas of life that are as strongly regulated and supervised as experiments in animals. We invest in Europe a lot in good care, good Animalia, in the ethics of experimentation, replacing animal experiments when there are good alternatives. I do not see any scientist doing experiments in animals for no good reasons. The only effect, when forbidding animal experiments in Italy and Europe will be that they go on in other countries where there is much less regulation.
I wonder what Italy will do once a medication has been found for AD by experiments in animals in other countries. Will it forbid its use because of the animal experiments???

Professor Francesca Pistollato is misleading the public and what she is saying is a big danger for the progress of research in the field of Alzheimer research.

Bart De Strooper