January 23, 2017

Researchers Create UV Activated Molecule to Control Inflammation

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Ice packs, painkillers and elastic bandages are silent attendees at any sporting event. Capable of soothing sprains and bruises, athletes the world over depend on their support.

But swollen and painful joints are not simply a byproduct of physical exertion. In fact, according to the Centers for Disease Control and Prevention, approximately 1 percent of the world’s population suffers from rheumatoid arthritis and complains of similar symptoms. Its socioeconomic effects are incalculable. Simple painkillers are incapable of mitigating the pain patients suffer.

Consequently, they have to turn to powerful immunosuppressants that have significant side effects. However, promising new research at Cornell University’s College of Veterinary Medicine could soon lead to alternative treatments without these unwanted effects.

Image courtesy of Prof. Pamela Chang

Light activated chemical probe scan be used to selectively turn off inflammatory activities of immune cells that were irradiated by light. Irradiated cells are shown in red, inflammatory molecules in cyan and light is the dotted line.

Light activated chemical probe scan be used to selectively turn off inflammatory activities of immune cells that were irridated by light. Irridated cells are shown in red, inflammatory molcules in cyan and light is the dotted lineLed by Prof. Pamela Chang, microbiology and immunology, researchers have created a molecule that, when exposed to UV radiation, is capable of controlling immune responses and thus, tackling inflammation.

“In the clinic, current therapies include drugs that modulate inflammation systemically and they often have off-target or side effects to the healthy, surrounding tissue. We hope to improve on these methods by developing technologies that are selective or specific to the target or affected tissue,” Chang said.

Enzymes, known as Histone Deacetylases, are responsible for regulating inflammation when the immune system detects any danger to tissue, such as from pathogens or physical damage. When the danger has passed, HDACs release inhibitors capable of suppressing such an inflammatory response. Chang’s molecule activates these inhibitors in the presence of UV light generated by unnatural, high-powered sources.

HDAC inhibitors are used to treat cancer and neurodegenerative diseases but are known to detrimentally affect heart function. According to Chang, this new technique could prevent such side effects because its selective targeting ensures that HDACs all over the body aren’t affected.

Consequently, doctors have better control over treatment procedures that target chronic inflammation. Immune responses continue normally except at the specific locations at which UV light is targeted and only during well-defined time periods of exposure. The technique also prevents infections that would be a byproduct of a weakened immune response, if drugs that affected HDACs throughout the body are used.

Chang believes that the technique could help alleviate the pain of patients suffering from diseases like asthma, rheumatoid arthritis, multiple sclerosis and colitis. Existing clinic infrastructure for similar procedures gives rise to enthusiasm that the procedure could eventually make an easy transition to hospitals and medical care centers all over the country. Chang insists, however, that work remains.

“Currently we have not identified any side effects of our technology, but we are limited in the dose that we can administer due to the toxicity of the photo-caged inhibitor at high doses,” Chang said. “We plan to test our methods in vivo with mice to demonstrate its viability for clinical use and are currently working on improving the selectivity of our approach for the target tissue.”

Bibudha Parasar, grad was a co-author on the study, titled “Chemical optogenetic modulation of inflammation and immunity” that was published in Chemical Science’s October issue.