New Treatment for Inflammatory Disease Uses Optogenetic Tool

An optogenetic approach to regulating inflammation and immunity in the human body employs photocontrolled histone deacetylase (HDAC) inhibitors that are selectively delivered to the target cells via UV radiation. This novel approach could further the study of inflammation and the immune system, and could ultimately lead to a means to control inflammation in vivo, while minimizing side effects to healthy tissues.

Researchers at Cornell University developed a chemical probe to target and activate HDAC inhibitors in the presence of UV light. Experiments showed that exposing the HDAC inhibitor to mild UV irradiation led to the selective release of the inhibitor in a spatiotemporal manner. This methodology was used to decrease the amount of pro-inflammatory mediators produced by a subpopulation of macrophages.

This fluorescence image demonstrates how light-activated chemical probes were used to selectively turn off inflammatory activities of immune cells that were irradiated with light, denoted by the dotted line. Irradiated cells are shown in red, and inflammatory molecules are shown in cyan. Courtesy of Bibudha Parasar.

The researchers’ approach could be especially useful as a therapeutic for inflammatory diseases because HDACs are ubiquitous in the body and have other biological effects; and most drugs for treating inflammation affect the entire system, leading to unintended consequences.

"If you turned off all the HDACs in the body, you would probably be hitting a lot of pathways that you didn't want to turn off," said professor Pamela Chang. "We can control when and where we turn off the HDACs using light. The idea is that you can actually target the tissue that has chronic inflammation and regulate it by selectively inhibiting HDACs in the tissue that's affected."

The strategy for modulating inflammation and immunity in a spatiotemporal manner using a photo-activated HDAC inhibitor shows promise for the selective delivery of therapeutics.

"Currently, there aren't a lot of tools that are able to manipulate the immune system in a spatiotemporal fashion," said researcher Bibudha Parasar.

Photodynamic therapies are being developed in the Cornell lab for the potential use of the tool to inhibit inflammation in patients with inflammatory diseases, Chang said.

The research was published in Chemical Science (doi: 10.1039/c6sc03702j).