Cornell scientists said they created a chemical tool that uses ultraviolet light to track inflammation and even control it. Their hope is it might work to treat inflammatory diseases, perhaps even multiple sclerosis.
An ultraviolet chemical tool has been developed that has the ability to observe and control inflammation. It will allow scientists to study immune response and may one day work to treat inflammatory diseases while sparing healthy tissue.
Researchers from Cornell University used chromatin-modifying enzymes including histone deacetylases (HDACs) in order to develop a strategy to regulate, observe, and control the HDAC inhibitors. The researchers added that immune cells like macrophages are mediated at the transcriptional level by these HDACs. The investigators additionally learned that the inhibitors can be selectively delivered to target cells by ultraviolet irradiation to minimize off-target effects, they wrote.
The study authors described their approach in a Chemical Science paper saying, “the inhibitor is released in the vicinity of or within the activated macrophages to decrease inflammation through change in gene expression.” Other methods similar to this have been used to photocage HDAC inhibitors, the researchers explained, but their approach differs because it uses HDACs within live cells to influence their cellular behavior and function.
The researchers believe their strategy can be utilized in the treatment of many inflammatory diseases, adding that one of the benefits of their strategy is that it can avoid undesirable side effects such as immunosuppression of other tissues, potentially leading to infection.
“We are pushing the forefront of developing new technologies to control inflammation and the immune system, with the ultimate goal of being able to study these biological pathways and perhaps develop therapies for inflammatory diseases,” first author, Pamela Chang, PhD, said in a press release. “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. 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 researchers said their hope is that their method can be utilized to treat many disorders related to inflammation, including autoimmune diseases as well as cancer. They continued that HDAC inhibitors like suberoylanilide hydroxamic acid (SAHA) — a competitive inhibitor or class I and II Zn2+ dependent HDACs that bind within the active site in the enzyme, according to the paper — have been well studied and are already approved by the US Food and Drug Administration. SAHA also contains anti inflammatory effects on multiple immune cell types, the study authors said.
Because of this, they wrote, selectively delivering some of the ultraviolet activated HDAC inhibitors could bring about positive and desirable physiological outcomes.
“Treatment-wise, our tools could be used for targeted inhibition of inflammation,” Chang told MD Magazine in an email. “This [multiple sclerosis treatment] would be an interesting future direction, but first we will need to test in animal models of disease. I don’t think MS would be the best disease to try because it is systemic, but perhaps other diseases that have localized inflammation and would be accessible to UV light such as irritable bowel disease, allergy, and some cancers. The advantage of our approach is its targeted nature so that we can avoid off-target effects on healthy surrounding tissue.”
The study is titled, “Chemical optogenetic modulation of inflammation and immunity.”