NanoSCA3: Development of brain-targeted nanobodies for application in spinocerebellar ataxia type 3 therapy
Ataxia UK
i3S consortium
SCA3 is caused by the expansion of a polyglutamine segment in the ataxin-3 protein, which accumulates protein aggregates. Small variable domains of camelid heavy-chain-only antibodies, known as nanobodies, show promise as therapeutic anti-aggregation agents for other neurodegenerative disorders, such as Parkinson’s Disease, Huntington’s Disease and Alzheimer’s Disease. This group holds a collection of ataxin-3-targeting nanobodies, seven of which impact on pathogenic ataxin-3 aggregation in vitro. In this project, they will investigate the neuroprotective potential of these nanobodies in cellular and Drosophila models of SCA3. Promising nanobodies will be engineered for blood brain barrier transmission and optimised for safe use in humans. If this project is successful, then these optimised nanobodies would then need to be tested in SCA3 mouse models, before eventually being tested in a clinical treatment trial in people with SCA3.
5.1 Pharmaceuticals