Conference Presentation, Panel, Roundtable
New Pathways to Neuroscience Breakthroughs
Milken InstituteRick Berke, Cara Altimus, Jeffrey Borenstein, Niranjan Bose, Johannes Streffer, Mike Belville, David Mongeau, Janet Knupp, Jing Lu, Ian Kramer, Anna McAllister
- The number of Americans living with dementia is projected to double over approximately 30 years, creating a potential "bigger train wreck" if healthcare spend continues at 3.6 or 3.7 trillion dollars without a solution.
- Current treatment landscape faces a critical gap where no drug slows or stops Alzheimer's disease since the last approval in 2003, and a nine-year lag exists between symptom onset and help for bipolar disorder and schizophrenia.
- Success depends on early detection a decade before clinical presentation, necessitating a shift from prevention to identifying physical markers, as current diagnostic methods struggle with overlapping symptoms and the inability to stop neurodegenerative processes once they accelerate.
- Research strategies must diversify beyond the two decades of overinvestment in the amyloid cascade hypothesis, which has provided conflicting results and biomarkers but no treatment success, to include top-down and bottom-up approaches and "shots on goal" for alternative hypotheses.
- Technological advances in whole-brain imaging, molecular specific markers, and longitudinal data are being developed to measure activity in behaving individuals, though the BRAIN Initiative tools are not yet fully utilized for diagnostics.
- Broader access to retrospective and prospective clinical data is deemed essential, with initiatives like an Ontario cross-condition analysis and Fox Foundation studies aiming to link comorbidities, identify genetic drivers, and monitor behaviors such as sleep and social media engagement.
- Innovative trial designs are required to handle long chronic diseases, balancing early targeted de-risking with later broad applicability, while acknowledging that futility analyses often involve decisions based on incomplete data.
- Philanthropy, including the Gates Foundation's nearly $150 million investment, is critical for de-risking early-stage science, accelerating funding without waiting for peer review, and supporting young scientists whose average age for NIMH support is increasing.
- Industry consolidation is expected as small neuroscience firms with promising data are acquired by large pharmaceutical companies, though big pharma previously exited due to capital returns, requiring long-term stamina from companies to de-risk development.
- Emerging therapeutic modalities include rapid-acting antidepressants effective in hours rather than weeks, stem cell-based testing for personalized medicine, and cognitive stimulation to help patients cope, alongside wearable algorithms developed with direct patient input.
- Structural challenges include a decreasing number of MD/MD-PhD researchers, the need for patient-centric outcomes like occupational markers over traditional biomarkers, and the necessity for policy and infrastructure changes to facilitate trial participation.
- Future progress relies on funding mechanisms that bridge the gap for preliminary data, sovereign wealth funds addressing aging populations, and collaborative advocacy efforts that avoid "disease wars" to lift all brain-related health sectors simultaneously.