Causal Influence: Overcoming Clinical Development Challenges for CNS Drugs

Michael Johnson, Professor of Neurology and Genomic Medicine at Imperial College London, delivered this presentation about the role of causal inference in drug development, particularly for Parkinson's disease. Johnson began by highlighting the high failure rates in clinical drug development, especially for CNS drugs, and emphasised the need for better target validation and biomarkers to improve success rates.

Johnson explained the concept of Mendelian randomisation and genetic colocalisation as methods to establish causal relationships between genetic variants and disease outcomes. He illustrated how these methods could inform therapeutic strategies by identifying disease-modifying drug targets and predictive biomarkers. Johnson provided an example of the failed attempt to repurpose Exenetide for Parkinson's disease, which underscored the importance of better target validation.

The presentation also detailed the Landmark Consortium, a large public-private partnership led by Johnson, aimed at identifying drug targets and predictive biomarkers for Parkinson's disease. The consortium involves collaboration between various stakeholders, including Imperial College London, Parkinson's UK, and several global pharmaceutical companies. Johnson discussed the consortium's plan to generate data on 400 genotyped human brains, both control and Parkinson's brains, and to conduct large-scale measurements of biological exposures across multiple modalities.

Johnson emphasised the value of public-private partnerships in accelerating drug development, providing access to resources and data, and fostering open innovation. He highlighted the financial and societal benefits of such collaborations, including the acceleration of drug discovery and the fulfilment of academia's contract with society to improve public health.

In summary, Johnson's presentation underscored the importance of causal inference in drug development, the challenges in CNS drug development, the role of the Landmark Consortium, and the value of public-private partnerships in advancing medical research.