Elaine Yang | November 17th, 2024
As the organ that governs everything from memory and movement to emotions and consciousness, the brain is remarkably intricate. Although we know a lot about biological connections in the brain, we do not completely know how neurons collectively operate to create perceptions, thoughts, memories and behavior. This makes it especially difficult to unravel and address the root causes of disorders, from Alzheimer’s to schizophrenia. Here at Vanderbilt, the Warren Center for Neuroscience Drug Discovery (WCNDD) seeks to redefine our understanding of human disease and the drug discovery process.
Led by Dr. Craig Lindsley, the WCNDD bridges the gap between basic science and patient care, focusing on translating new insights into treatments for neurological disorders. While the pharmaceutical industry often avoids the risks of untested therapies, the WCNDD explores novel drug targets for complex brain conditions, like Alzheimer’s and Parkinson’s, that traditional pharmaceutical settings may overlook. By conducting early-stage research within an academic framework, the center pushes promising discoveries toward clinical readiness, reducing the risks associated with innovative therapeutic development. Adopting a dual “bench to bedside” and “bedside to bench” approach, the WCNDD ensures that observations from real-world patient interactions are used to guide further research. This cycle enhances the chances of developing therapies tailored to the unique biology of neurological conditions.
Breakthroughs and achievements
As a clinical-stage biotech center nestled within Vanderbilt, the WCNDD currently has three Phase 1 compounds undergoing clinical trials. Clinical trials are imperative in drug design, as they allow researchers to evaluate the efficacy and safety of the potential treatment before allowing it to be widely administered to patients.
A drug candidate for the treatment of Parkinson’s disease that was discovered at the Vanderbilt WCNDD began Phase 1 clinical testing at Appello Pharmaceuticals. This drug candidate, which modulates one type of receptor for the neurotransmitter glutamate, is designed to be used alongside the current Parkinson’s disease treatment, levodopa. When used alongside levodopa, the drug extends the duration of symptom relief while minimizing debilitating side effects like dyskinesias, which are uncontrollable involuntary movements characteristic of the disease.
The WCNDD has also made advancements in identifying new treatments for previously untreatable dementias, including Alzheimer’s disease, which is another one of the WCNDD’s areas of focus. Dementias like Alzheimer’s often overtake the brain by spreading misfolded protein from one area to another, like a chain reaction. Dr. Lindsley and fellow researcher Dr. Jeffrey Conn, found that stimulating a receptor crucial in memory and learning could help reduce neuroinflammation and the adaptive changes associated with neurodegeneration caused by misfolded protein spread. This breakthrough is currently being tested through the use of one drug in collaboration with Acadia Pharmaceuticals.
More recently, a potential treatment for schizophrenia that was developed by the WCNDD achieved FDA approval for Phase 1 clinical trials, initiated by Neumora Therapeutics. It utilizes a mechanism that has already been clinically proven to be effective in treating conditions such as schizophrenia, targeting the area of the brain that regulates the transmission of the neurotransmitter dopamine. Dopamine plays an important role in the pathology of schizophrenia: studies have shown that abnormal dopamine levels in certain regions of the brain are characteristic of the disorder. Thus, the restoration of balance in the brain’s dopamine pathways is key in alleviating symptoms and improving overall function for individuals with schizophrenia.
Future implications
The advances made at the WCNDD hold promising implications for the future treatment of complex brain disorders. The center’s innovative approach to drug discovery could significantly reshape how neurological conditions are treated, offering hope to millions affected by diseases like Parkinson’s, Alzheimer’s, and schizophrenia.
By developing innovative therapies — modulators to enhance levodopa for Parkinson’s, targeting specific receptors to combat neuroinflammation in Alzheimer’s, and regulating dopamine pathways in schizophrenia — WCNDD is moving beyond symptom management to address the root causes of these conditions. By “de-risking” new treatment strategies with transformative potential by investing in early-stage research that pharmaceutical companies often avoid, the WCNDD provides strong validation for groundbreaking approaches to severe neurological disorders. This model not only accelerates high-risk research but also serves as a blueprint for other institutions, expanding personalized medicine and driving a new era of transformative patient care.
Cover photo courtesy of Warren Center for Neuroscience Drug Discovery
References
Brisch, R., Saniotis, A., Wolf, R., Bielau, H., Bernstein, H. G., Steiner, J., Bogerts, B., Braun, K., Jankowski, Z., Kumaratilake, J., Henneberg, M., & Gos, T. (2014). The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Frontiers in psychiatry, 5, 47. https://doi.org/10.3389/fpsyt.2014.00047
Research News. (2021). Vanderbilt-discovered drug candidate for Parkinson’s disease enters clinical trials. Research News at Vanderbilt.
Research News. (2022). Vanderbilt, international collaborators discover treatment to slow neurodegenerative diseases. Research News at Vanderbilt.
Research News. (2023). Potential schizophrenia treatment, discovered at Vanderbilt and being developed by Neumora Therapeutics, entering Phase 1 clinical trial. Research News at Vanderbilt.
Roland, P.E. (2023). How far neuroscience is from understanding brains. Frontiers in systems neuroscience, 17, 1147896. https://doi.org/10.3389/fnsys.2023.1147896
