AINEWS
Bryan Roth, who built the DREADD (designer receptor) brain circuit switch two decades ago, learned from a public database that at least seven Chinese clinical trials are now testing it in patients.
Bryan Roth of the UNC School of Medicine told an audience of US researchers at the NIH BRAIN Initiative meeting in Bethesda this week that at least seven clinical trials in China are already testing a brain-circuit therapy he invented two decades ago. He found out about the trials from a database search, not from the trial teams themselves.
Chemogenetics works like a light switch engineered into specific brain cells. A virus delivers a designer receptor gene into a small group of neurons, and a small-molecule drug (in the new trials, the antipsychotic clozapine) binds only to that engineered receptor, silencing the targeted cells and the circuits they belong to. The receptor binds clozapine with picomolar affinity, orders of magnitude more sensitive than any natural human receptor, which is what lets a single dose turn off a defined brain circuit.
Translating that idea into a clinical product is a three-part engineering problem: a viral vector, a designer receptor gene, and a small-molecule agonist. The US venture and regulatory ecosystem is structured to underwrite single-target drugs, not stacked gene-plus-vector-plus-pill products. In Roth's telling, he was approached about commercializing DREADDs and "nobody wanted to take the risk."
Two months ago, a rumor about designer-protein brain therapies prompted Roth and a postdoc to search the US and Chinese clinical trial registries. They found seven studies covering intractable epilepsy, Parkinson's disease, and neuropathic pain. The registry entries are visible to any researcher with a browser, and Roth's US colleagues learned about them only at this week's meeting.
Dirk Trauner of the University of Pennsylvania characterized the approach as "a more precise knife" than small-molecule drugs aimed at natural brain receptors, which can hit unrelated circuits and produce off-target effects. That framing is one researcher's verdict, not consensus.
The mechanism explains why DREADDs were a research workhorse for twenty years without reaching a clinic. The counterargument is a US pharma or biotech program already running an undisclosed DREADD trial; if so, the inventor's "nobody wanted to take the risk" testimony would be wrong. Roth's account is the only public statement of why no US sponsor moved.
Until the trial sponsors release outcome data, the registry entries are the public record. US researchers will be watching what crosses the wire from Chinese clinical sites first. Community concerns about bioethics, prion-like risk scenarios, and a separate research-subject death surfaced in a Hacker News thread on the C&EN piece; those are not adjudicated by the source and remain open questions for the trial sponsors and regulators to address.