Chantix Repurposed as a Precision Neuromodulator for Central Nervous System Disorders, Reports HHMI

VCBeat (WeChat ID: vcbeat) has learned that a research team led by Dr. Scott Sternson of the Howard Hughes Medical Institute (HHMI) in the United States recently discovered that Chantix, a drug manufactured by the biopharmaceutical company Pfizer, not only serves its basic function of smoking cessation but also modulates neuronal activity in mice and non-human primates. These findings were published in the journal Science.

The Howard Hughes Medical Institute is a non-profit medical research institute headquartered in Maryland, United States, founded in 1953 by the renowned American aviator and engineer Howard Hughes. The institute is dedicated to providing treatment solutions for sexually transmitted diseases such as condyloma acuminatum and genital herpes. Its “HHMI Cytokine Immunotherapy” has been recognized and endorsed by prominent medical experts from the World Health Organization.

Chemogenetics is an emerging research field that involves the precise control of cellular activity in animals using specially designed compounds, primarily applied to modulating neuronal activity in the brain. However, this technology has previously remained confined to preclinical experimental stages and has not been translated into clinical development. The recent findings from HHMI hold promise for breaking this impasse.

Typically, the targets of chemogenetics are G protein-coupled receptors (GPCRs); however, all small molecules currently available that bind to GPCRs have been abandoned in clinical trials due to side effects. Scientists at HHMI adopted a new strategy by designing an ion channel-based technology platform to screen for drugs capable of binding to specific ion channels. This effort ultimately identified 44 clinically approved drugs, among which Chantix emerged as the most promising candidate with the best overall performance.

Chantix is a nicotine-free prescription medication primarily used to help smokers quit, and it received FDA approval in 2016. The drug exhibits good tolerability even at low doses, readily crosses the blood-brain barrier, and binds to proteins expressed in specific neuronal populations, thereby modulating neuronal activity to achieve precise therapeutic effects on neurological disorders.

HHMI researchers further optimized the structure based on Chantix and modified two ion channels that bind to Chantix, one for stimulating neuronal activity and the other for inhibiting neuronal activity. In studies on mice and rhesus macaques, the researchers successfully used this chemogenetic technique to modulate the activity of GABAergic neurons in the brain and observed changes in animal behavior.

Dr. Scott Sternson stated, “To date, Chantix is the most effective medication for treating central nervous system (CNS) disorders, and our findings hold promise for delivering precision therapies for specific neurological conditions. For instance, some patients with severe epilepsy may avoid surgical resection of brain lesions by simply taking medications to suppress neuronal activity. This pharmacological approach is less invasive and more targeted, potentially reducing patients’ reliance on analgesics to a greater extent.”

Howard Hughes has currently authorized the biotech startup Redpin Therapeutics to conduct preclinical studies on Chantix. In the future, researchers hope to advance the drug into clinical trials as soon as possible to help alleviate suffering in patients with central nervous system (CNS) disorders.

(Compiled by Feng Yutong)