Chantix Used for ‘Mind Control’ in Chemogenetics Study

Chantix Used for ‘Mind Control’ in Chemogenetics Study

The collaborative research team was able to turn neurons on and off using Pfizer's anti-smoking drug, demonstrating the power of chemogenetics in a preclinical setting.

If human behavior results from different chemical reactions, then mind control might be achieved by selectively altering chemicals in the brain. That’s the principle behind chemogenetics, the focus of a new research article published in the prestigious journal, Science.

“Chemogenetics is a method for controlling ion flux in cells, and nearly all cells are influenced by ions,” said Dr. Scott Sternson, senior author and group leader at the Howard Hughes Medical Institute’s Janelia Research Campus, in an email interview with Xtalks.

But when ion flux is manipulated in the brain, the result is control over neural activity and thus control over behavior. The researchers developed a chemogenetics system to activate or silence mouse neurons in the presence of Chantix (varenicline), Pfizer’s popular anti-smoking drug.

Chemogenetics involves engineering a receptor that is administered by gene therapy then pairing that with a small molecule agonist. Presently, the researchers engineered one receptor that stimulates neural activity when varenicline binds and another receptor that silences neural activity when varenicline binds.

“We showed that when we used our chemogenetic system to inhibit neurons in a brain area called the substantia nigra reticulata on only one side of their brain, mice would run in circles opposite to the side of the brain that was silenced,” Dr. Sternson explained. “This is because this brain region normally suppresses movement, and thus inhibiting these neurons consequently activated movement on one side of the body, hence the circling behavior.”

Out of many drugs capable of crossing the blood-brain barrier, why did the researchers choose a smoking cessation aid? In addition to having long-lasting effects, evaluating an already-approved drug has important implications for clinical use.

“The idea was that if chemogenetics was ever to be used therapeutically in people, then it would reduce risk to use an already-approved-drug that was known to be safe and well tolerated at already defined doses in people,” said Dr. Sternson. “Our use of FDA-approved varenicline at very low doses to control the chemogenetic receptors facilitates translation.”

A highly sensitive and selective chemogenetics system means even very low doses of Chantix can achieve the desired effect. These features could minimize the number of off-target effects, which is a pervasive problem in drug development for neurological diseases.

Continuing R&D and safety studies of this chemogenetic system is Redpin Therapeutics, a New York-based gene therapy company co-founded by Dr. Sternson and others. The company seeks to build on the researchers’ findings and eventually proceed to in-human trials.

“The breakthrough discoveries unearthed by Scott and his colleagues have paved the way for Redpin to lead the clinical application of chemogenetics, which up until this point has not been possible,” said Dr. Elma Hawkins, president and CEO of Redpin and a co-founder of the company, in a press release. “We are advancing a pipeline of first-in-class gene therapies for critical unmet needs of patients with neurological and psychiatric disorders.”

While no chemogenetic gene therapies have successfully obtained FDA approval, there is no shortage of research on this novel therapeutic. Last year, CODA Biotherapeutics received $19 million in Series A financing from major pharma investors to develop new treatments for chronic neuropathic pain.

As scientists refine their understanding of chemogenetics, it’s possible that “mind-controlling” drugs will soon be used in the clinic.