Project Manager
Sehlin, DayProject manager
Uppsala UniversityAmount granted
1 000 000 SEKYear
2019
Neurodegenerative diseases such as Alzheimer's and Parkinson's currently lack effective treatment. The most promising strategy is immunotherapy, where antibodies are administered to neutralize the proteins amyloid-β (Aβ) that clump together and form plaques in Alzheimer's disease and alpha-synuclein (α-syn) that forms so-called Lewy bodies in Parkinson's disease.
Our previously developed antibody mAb158 is selective for protofibrils, a toxic precursor of the Aβ plaque, and its humanized form (BAN2401) has shown positive results in a large clinical trial involving 856 Alzheimer's patients. We have developed similar antibodies for α-syn. However, antibodies are large molecules that have difficulty entering the brain, so high doses must be administered to achieve an effect.
To increase brain uptake and thus the treatment effect, mAb158 has been linked to 8D3, an antibody that binds to the transferrin receptor, normally involved in the transport of iron. Like a Trojan horse, 8D3 then carries mAb158 into the brain, where it can neutralize the toxic protofibrils. Using imaging techniques, we have shown that this strategy leads to greatly enhanced antibody uptake in the brains of mice.
With this project, we want to conduct therapy studies with modified antibodies against both Aβ and α-syn in transgenic mice, comparing its effect with unmodified antibody and studying treatment mechanisms. We believe that this new treatment strategy is a prerequisite for achieving effective immunotherapy in brain diseases.