China stuns scientists with early success in DREADDs human testing

A lab in Beijing has found that DREADDs, a frontier neuroscientific method that until recently had never been used on humans, shows promise for treating epilepsy. 

The Chinese scientists reportedly reduced the frequency of seizures in three epilepsy patients with resistance to drug treatment by an average of 92.6%. They did this by changing specific receptors in the brain using a genetically-engineered virus and then triggering these receptors to switch a specific part of the brain off using a low-dose of clozapine.

The study found that the method, known as DREADDs or Designer Receptors Exclusively Activated by Designer Drugs, had a favourable safety profile, with adverse events deemed mild-to-moderate (grade 1 or 2).

Earlier this year, scientists around the world were left astonished by the news that China has begun human testing with DREADDs on patients with epilepsy, Parkinson's disease and chronic pain.

At a gathering of some of the world's leading experts in the US city of Bethesda, US, Professor Brian Roth – the inventor of DREADDs – told attendees at the NIH BRAIN Initiative meeting that at least seven human trials using DREADDs had been registered by Chinese laboratories, leaving the room in stunned silence. 

The news brought a blend of excitement and trepidation.

"Human testing with DREADDs is potentially really exciting because of all the potential benefits they have," Professor Ewan St John-Smith, Department of Pharmacology at the University of Cambridge, told CGTN. "As exciting as it could be to see this technology leap from bench to bedside, the question is whether it's ready."

Before China's move to human testing, DREADDs were neuroscience's most precise method for switching animal brain circuits on and off. They have already allowed scientists to make significant developments in medical and neuroscientific understanding. 

"DREADDs, alongside similar chemogenetic tools, are really powering neuroscience research at a much faster rate than say when I was doing my PhD," says Ewan St John-Smith, Department of Pharmacology at the University of Cambridge, who uses DREADDs in his own lab to research pain mechanisms. "They enable you to have much greater control of neurocircuitry."

For several of these diseases being studied, the current therapy of last resort involves surgically removing or ablating brain tissue. If DREADD therapy proves safe, it could offer a reversible and far less invasive alternative.

This is a leap no one outside of China has dared to attempt. Not least because the method comes with certain risks.

"From the research perspective, I think that they are amazing tools. In terms of translating those to humans and for therapy, I think there's a few things we need to consider," says St John-Smith. "Firstly, you're delivering these DREADDs via viral means, so you've got the whole long-term potential issues surrounding using those viruses.

"The other factor to consider is if you make this DREADD be produced inside a cell, even though it can't be activated by a substance within the body, it's still perturbing the normal cellular environment," he continues. "Even if it's not being activated, it's still going to be altering the cellular homeostasis."

China's move to begin human trials comes alongside other recent world firsts in neuroscience. Earlier this year, China approved its first brain implant for commercial use to help people with spinal cord injuries. 

Researchers around the world are taking notice. "If I think back to my PhD 25 years or so ago, the main research powerhouse was really the US. That has been transformed, I think, in the last 10 years. Neuroscience research in particular in China has taken off," says St John-Smith.

"There's huge numbers of high-impact, exciting papers coming out. When you visit research institutes there, you can really see how much money has been going into these institutes to build state-of-the-art facilities and how much research funding is being produced," he adds.

The results of these early human trials are important. If DREADDs prove safe and effective, we could see other countries rapidly moving towards clinical trials, potentially offering unprecedented hope for millions living with chronic neurological conditions.