Upscaling human stem cell assays to detect autoantibodies in central nervous system diseases

The award will allow Lahiru to purchase equipment to establish the first human stem cell-based research facility for autoantibody-mediated brain disorders in the UK, supplying the neuroimmunity community with cells to replace an assay that uses cerebrospinal fluid collected from the brains of neonatal rats. The funding also supports the development of a new platform for sharing methodologies and control data.

This award was made as part of the 2024 non-animal methods infrastructure grants supported with funding from the Department for Science, Innovation and Technology (DSIT).

There is growing evidence for the role of autoantibodies in common and debilitating disorders affecting the brain, such as psychosis and dementia. Autoantibodies, fortunately, can be effectively and safely treated by targeted immunotherapy. Therefore, accurately identifying individuals who harbour these autoantibodies offers a crucial opportunity to improve their long-term health.

One of the biggest barriers to identifying autoantibodies targeting the brain is the lack of appropriate model systems. Currently, the most widely used assays are based on rat neurons. These assays are limited because they 1) require a large number of foetal rat brains and, 2) are not fully reflective of the complexity of human brain receptors. Thus, developing and upscaling human stem cell based neuronal assays offers a much more attractive approach. Accordingly, in this application, we propose to develop a stem cell research facility that can generate human neuronal assays to detect and discover autoantibodies in a scalable manner, whilst overcoming barriers that arise from using rat brains. This will also lay the foundations to fully replace the use of animal use in this field.

This facility will be developed through two approaches. First, the facility will be physically based at and available to all researchers at the University of Oxford, a leader in the field of autoantibody discovery in brain health disorders. Second, the knowledge gained through this facility will be made openly available to researchers in neuroimmunology laboratories across the UK via an online data platform.

Overall, this will serve as the first stem cell based clinical research facility for autoantibody mediated brain disorders in the UK; and importantly we will work with the wider network of neuroimmunology laboratories to accelerate the adoption of this non-animal methodology across the UK.