Chemogenetics, a technique that modifies specific neurons to be controlled by inert drugs, is currently undergoing human clinical trials, as reported by Bryan Roth at the BRAIN Initiative conference on August 13. Roth identified seven ongoing clinical trials in China focused on using chemogenetics for conditions such as epilepsy, Parkinson’s disease, and pain. Chemogenetics, which includes designer receptors exclusively activated by designer drugs (DREADDs), allows for targeted modulation of neurons, potentially offering new therapeutic options for neurological disorders.
The technique is similar to optogenetics, which uses light to control neurons, but chemogenetics enables control through designer chemicals. This method allows for more precise targeting of neurons, which could lead to improved treatments for conditions like refractory epilepsy, where traditional treatments often affect overall brain activity rather than specific areas.
Roth's findings indicate that three of the trials are targeting epilepsy, a condition characterized by uncontrolled seizures that can significantly impact a person's life. Current treatments often involve broad-spectrum medications that can cause side effects, highlighting the potential benefits of a more targeted approach using chemogenetics.
The ongoing trials involve the use of a modified human muscarinic receptor, hM4Di, which can be activated by a designer drug. Patients receive an injection of a viral vector that delivers the gene for this receptor, allowing for modulation of neuronal activity when the appropriate drug is administered. Although the results of these trials are not yet available, preclinical studies in non-human primates have shown promise in reducing seizure activity.
While chemogenetics offers a reversible and potentially safer alternative to gene editing, there are challenges, including the need for precise targeting and the risk of drug interactions. The ongoing research aims to refine these techniques and explore additional receptor options to enhance the effectiveness and safety of chemogenetic therapies.