APR 30, 2019 12:05 PM PDT

Using a popular anti-smoking drug to control brain cells

Designer receptors exclusively activated by designer drugs, or simply called designer receptors, are specially engineered proteins that are used to control the activity of neurons. Specific drugs bind very precisely to the receptors to turn them on, similar to a lock-and-key mechanism, and this causes an increase or decrease in neural activity of the cell. By placing these receptors only in certain groups of neurons, scientists can very precisely control this group of cells while leaving other cells unperturbed.

For two decades, this method, called chemogenetics, has worked exceptionally well to control neurons in rodents, and more recently in non-human primates, for research applications. Scientists have spent years matching drugs with receptors to achieve precise and effective combinations, yet making this technology feasible for clinical use in humans has been challenging.

Other scientists working on this approach "often use molecules that would not be appropriate for human therapy," Sternson says. "It's still many steps to the clinic, but we're trying to shorten that route."

Rather than creating a new drug, Scott Sternson, a group leader at the Howard Hughes Medical Institute's Janelia Research Campus, took a different approach by sifting through existing FDA-approved drugs, and upon finding a viable candidate, tweaked the structure of the drug's receptor.

Sternson and his team decided on varenicline (i.e. Chantix(R)), a commonly prescribed drug that reduces nicotine cravings. Then, the research group modified the structure of two ion channel proteins to make varenicline bind extremely well to the receptor. One receptor makes neurons more active, and another shuts them down or silences cells when the drug is on board, just like traditional designer receptors. The best part about the drug? It can be used in ultralow doses to control neurons, which means less unwanted side effects in people.

Photo source: Forbes/ Bloomberg

"These are the most potent chemogenetic receptors described so far," Sternson says. Even low doses of varenicline -- well below the level used for smoking cessation -- can have a big effect on neural activity. 

In the lab, chemogenetics is widely used by neuroscientists to study how neural activity is related to animal behavior. Sternson and his team, however, seek to use chemogenetics to treat human diseases. The ability to turn specific cells on or off with precision is the future of therapeutics. For example, Sternson believes the technology may be used to treat pain by targeting only injured parts of the body. This is important for reducing the incidence of addiction to pain killers. Another example is severe epilepsy. Rather than surgically remove parts of the brain associated with seizures, designer receptors can be placed into neurons in these regions and patients could take a drug that targets and/ or regulates these specific cells.

Source: ScienceDaily

About the Author
You May Also Like
AUG 31, 2020
Genetics & Genomics
A Treatment Avenue Opens for a Rare Disorder
AUG 31, 2020
A Treatment Avenue Opens for a Rare Disorder
Krabbe disease or globoid cell leukodystrophy is a rare and deadly disorder that affects about one in every 100,000 infa ...
SEP 10, 2020
Drug Discovery & Development
Common Painkiller Increases Risk-Taking Behavior
SEP 10, 2020
Common Painkiller Increases Risk-Taking Behavior
Researchers from Ohio State University have found that the common painkiller, paracetamol ( also known as Tylenol and Pa ...
SEP 16, 2020
Immunology
Depression, but Not Anxiety, Causes Inflammation and Metabolic Imbalances
SEP 16, 2020
Depression, but Not Anxiety, Causes Inflammation and Metabolic Imbalances
Scientists have discovered that depressed individuals show higher levels of inflammation as well as elevated fat concent ...
SEP 29, 2020
Cell & Molecular Biology
What We Call Parkinson's Disease May Actually be Two Distinct Disorders
SEP 29, 2020
What We Call Parkinson's Disease May Actually be Two Distinct Disorders
Researchers have used imaging tools to show that Parkinson's disease may actually be two different diseases, one that st ...
OCT 12, 2020
Neuroscience
Effects of Oxytocin Depend on Where it Comes From
OCT 12, 2020
Effects of Oxytocin Depend on Where it Comes From
Oxytocin has gained its reputation as the 'love hormone' for its role in regulating prosocial behaviors like emp ...
OCT 29, 2020
Clinical & Molecular DX
Skin Deep: A Novel Test for Parkinson's
OCT 29, 2020
Skin Deep: A Novel Test for Parkinson's
In Parkinson’s disease (PD), there is chronic degeneration of the central nervous system, particularly in the regi ...
Loading Comments...