Periodic Reporting for period 1 - AD-VIP (Alzheimer’s disease and AAV9: Use of a virus-based delivery system for vectored immunoprophylaxis in dementia.)
Berichtszeitraum: 2016-12-01 bis 2018-05-31
Alzheimer's Disease (AD) is the most common form of dementia worldwide. The number of cases is increasing year-on-year, and it is currently untreatable, making it a major issue for western societies.
The amyloid hypothesis states that accumulation of amyloid-beta peptide (Aβ), in the brain of AD sufferers, is toxic - causing neurodegeneration and cognitive decline. Aβ is formed by sequential cutting of amyloid precursor protein (APP) by the enzymes BACE1 and gamma-secretase. Therefore, blocking the activity of these enzymes and reducing Aβ formation should alleviate AD.
Antibodies are made by the immune system to prevent infection. In part, antibodies are powerful because they are highly specific for their targets. This fact is often exploited in biology, where antibodies are made against important protein targets. This project has used an antibody which specifically targets BACE1, preventing its activity and reducing Aβ production in vitro.
Unfortunately, antibodies injected into the blood stream (as therapeutics) cannot enter the brain, as it is effectively shielded by the blood brain barrier (BBB). During this project, we developed a system that crosses this barrier, allowing us to deliver antibodies into the nervous system. Importantly, when this system was injected into a mouse model of AD, the anti-BACE1 antibody was able to significantly reduce levels of Aβ.
These results hold great socio-economic promise. First, data generated by this project can be exploited by pharma companies to develop next generation drugs to treat Alzheimer's disease. (Note the technology can, in principle, also be applied to other currently untreatable CNS diseases). Second, by enabling drug development, prospects for patients and their families are much improved.
The amyloid hypothesis states that accumulation of amyloid-beta peptide (Aβ), in the brain of AD sufferers, is toxic - causing neurodegeneration and cognitive decline. Aβ is formed by sequential cutting of amyloid precursor protein (APP) by the enzymes BACE1 and gamma-secretase. Therefore, blocking the activity of these enzymes and reducing Aβ formation should alleviate AD.
Antibodies are made by the immune system to prevent infection. In part, antibodies are powerful because they are highly specific for their targets. This fact is often exploited in biology, where antibodies are made against important protein targets. This project has used an antibody which specifically targets BACE1, preventing its activity and reducing Aβ production in vitro.
Unfortunately, antibodies injected into the blood stream (as therapeutics) cannot enter the brain, as it is effectively shielded by the blood brain barrier (BBB). During this project, we developed a system that crosses this barrier, allowing us to deliver antibodies into the nervous system. Importantly, when this system was injected into a mouse model of AD, the anti-BACE1 antibody was able to significantly reduce levels of Aβ.
These results hold great socio-economic promise. First, data generated by this project can be exploited by pharma companies to develop next generation drugs to treat Alzheimer's disease. (Note the technology can, in principle, also be applied to other currently untreatable CNS diseases). Second, by enabling drug development, prospects for patients and their families are much improved.