China launches first human trials of DREADD chemogenetic brain therapies
The discovery of at least seven clinical trials using designer protein receptors has stunned US neuroscientists who viewed the technology as too risky for human use.
US neuroscientists have discovered that China has launched at least seven clinical trials testing chemogenetic therapies in humans, a move that has sent shockwaves through the Western research community. The trials utilize a technology known as DREADDs to suppress specific neuronal signaling in the brain, marking a leap from animal research to human application that many in the US believed was still years away.
The discovery was revealed during a US National Institutes of Health (NIH) BRAIN Initiative meeting, where the news was met with what Bryan Roth, the inventor of DREADD technology and a professor at the University of North Carolina School of Medicine, described as "stunned silence." According to reporting by Chemical & Engineering News (C&EN), the Chinese trials are currently targeting three high-impact conditions: Parkinson's disease, neuropathic pain, and intractable epilepsy.
The Mechanics of Designer Receptors
Developed by Roth approximately 20 years ago, DREADDs—or "designer receptors activated by designer drugs"—allow for unprecedented precision in brain modulation. The process involves introducing synthetic receptors into specific neurons via viral vectors. Once these receptors are in place, they remain dormant until a specific small-molecule drug is administered, which then activates the receptors to either excite or inhibit the target neurons.
While this method has become a staple in animal research for mapping complex brain circuits, its transition to human patients has been stalled in the US. American researchers and regulators have largely viewed the technology as too risky for clinical use, citing safety concerns and the regulatory hurdles associated with introducing synthetic proteins into the human brain.
A Shift in Neuromodulation
The implications of these trials are significant. If successful, this approach could replace invasive brain surgeries—often the last resort for patients with intractable neurological conditions—with circuit-based therapeutics. By targeting specific neural pathways, DREADDs offer a path toward high-precision neuromodulation that avoids the widespread off-target effects common in traditional pharmacological treatments.
Roth noted that if these trials prove successful, it "opens the way basically to circuit-based therapeutics for virtually all neuropsychiatric diseases." The shift suggests a move away from treating the brain as a chemical soup and toward treating it as a series of electrical circuits that can be toggled on or off.
The Global Translation Gap
The revelation of these trials highlights a growing divide in the pace of neurotechnological translation between the US and China. Jacques Carolan, a neuroscientist at University College London, remarked that the development is clear evidence that "China is ahead in neuro."
What remains to be seen is the safety and efficacy data from these seven trials. While the US community remains cautious, the results from China may force a global re-evaluation of the risk-benefit ratio for chemogenetic therapies. For now, the international community is watching to see if this high-risk gamble will yield a new era of precision medicine for the brain.