When I started with Alzheimer’s research 30 years ago, I had a background to work as a clinical doctor and doing research on the patients I worked with. And that was a rare inherited disorder named acute intermittent porphyria. And starting with Alzheimer’s disease, I had a good background working with the families with the disease and was working with both biochemistry and genetics...
When I started with Alzheimer’s research 30 years ago, I had a background to work as a clinical doctor and doing research on the patients I worked with. And that was a rare inherited disorder named acute intermittent porphyria. And starting with Alzheimer’s disease, I had a good background working with the families with the disease and was working with both biochemistry and genetics. Very rapidly we found what was by the American named, the Swedish mutation which has been very much used in the field, especially in mouse model. The Swedish mutation had a very strong propensity to over produce amyloid beta. For me already 30 years ago, it was very clear that this is something that must be similar for all types of Alzheimer’s disease, as both clinical features and neuropathology is the same. Although these rare familial cases, they get the disease much earlier, often in their 50s, as in the case with the Swedish mutation.
And at that time, being 30 years younger and more naive, I thought it would take 10 years for us to develop effective treatments against Aβ. That was more complicated than we believed at the time. And then some years later, we found another family from Northern Sweden and a mutation in that family. We named that the Arctic mutation, as it was from that region of Sweden, and the Arctic mutation has a very interesting feature. It formed large soluble aggregates that we named protofibrils. I got the idea, and this was in 1999. That there came a very famous paper from a small biotech company in San Francisco, Athena Neuroscience, and they demonstrated how they could treat Alzheimer mice with immunotherapy.
And when as, I was very impressed by that paper. And I thought we should do the same, but we should not target Aβ in general. We should target a special form of Aβ, these soluble aggregates. Because my thinking was that the monomers can’t be toxic, because we have them from… All people have them, all cells produce them. They can’t be toxic. The end stage, the fibrils that we find in the plaques, they’re low… probably fairly inert. Then in my lab at Uppsala University, we managed to isolate a monoclonal antibody. We named it mAb158, and that antibody has those properties. So it has its strongest binding to the protofibril, very weak binding to monomers and 10 to 15 times weaker binding to fibrils. That antibody of our… Oh, I should mention that in 2003 I formed a company with a colleague that had experienced from the pharmaceutical industry, Pharmacia in Sweden.
And I’m a typical medical researcher, I don’t have that experience. And I realized that there were, we needed some other competences here. So, Pär Gellerfors is his name. We managed to make a deal with Eisai, the Japanese company, and mAb158 was humanized by the company we started. We named the company BioArctic, of the mutation. The BioArctic humanized mAb158, so it was named BAN2401. Now, lecanemab. So lecanemab is, we made a deal with Eisai, the Japanese company, yes. They now are conducting the clinical trials, and we’re now in Phase III. We have data from a large Phase II that looks very good, and we hope that we can replicate that data now in Phase III. We will know, in September in this year, we will have the data. If we can replicate Phase II data, I think we will have a new drug, on the market. I’m very confident and hopeful.
