Rebecca Seal

A major milestone for Chemogenetics. DREADD technology demonstrates therapeutic efficacy in humans. A new study published today in NEJM demonstrates preliminary safety and therapeutic benefit from DREADD-based chemogenetic treatment of refractory epilepsy, marking an extraordinary milestone for neuroscience and precision medicine. nejm.org/doi/full/10.1056/NE… The approach combines targeted AAV gene delivery at the epileptogenic locus with very low, subthreshold doses of clozapine to activate engineered DREADD receptors and modulate neuronal activity. Congratulations to Bryan Roth, whose pioneering discovery of DREADDs made this field possible, and to the investigators of the NEJM study for bringing this technology to patients. This achievement has a particularly meaningful connection to our work published in Science Magazine in 2017. science.org/doi/10.1126/scie… We showed that clozapine, rather than CNO itself, is the active mediator of DREADD activation in vivo and proposed that subthreshold doses of clozapine could be used to activate DREADDs in humans, anticipating a practical path toward clinical translation. At the time, many in the scientific community viewed these findings primarily as relevant to the design of preclinical DREADD experiments. We saw a much broader opportunity, translating Chemogenetics into human therapeutics. Nearly a decade later, that vision is now becoming a reality. Our 2017 study was supported by the research funding through the National Institutes of Health (NIH) and The National Institute on Drug Abuse (NIDA), a prime example of how fundamental basic research can ultimately enable transformative clinical applications. This is an exciting beginning, but larger, well-controlled studies are essential to establish the magnitude and durability of therapeutic benefit and long-term safety. Chemogenetics is moving beyond an experimental neuroscience tool toward a potentially transformative neuroscience platform. We are only beginning to realize its potential.