Instead of trying to suppress the latter stages of the inflammatory process in rheumatoid arthritis with drugs one group of VA researchers is taking a more proactive approach, with the understanding that early treatment is critical. They've tested a chemical compound that works to prevent an initial phase of tissue inflammation and improve one's immune system.

In this case, improvements in human system function mean the ability of a person to recover from inflammation, while also being able to fight infection; respond to vaccines; and identify and remove tumor–related cells, according to Goronzy and his research team. In addition, the rate of developing cancer declines by at least twofold due to treatment with the chemical, compared with a person who is not treated, they write.

Lab studies have suggested the compound, which is under a U.S. patent, might improve immune system function in patients with rheumatoid arthritis. In that condition, naive lymphocytes, mature immune cells that have not been exposed to an antigen, endure elevated amounts of DNA double–strand breaks, a sign of genetic instability. That pattern is often seen in people with rheumatoid arthritis, the recipients of bone marrow transplants, and adults age 50 or older.

Dr. Jorg Goronzy and Dr. Cornelia Weyand, another rheumatologist at the Palo Alto VA, led the lab testing. The two also hold academic appointments at Stanford University. Their team has used a human–mouse "chimera" model in which synovial tissue, which lines the cavities of joints and creates a fluid that helps the joints move smoothly, is taken from people with rheumatoid arthritis and implanted into a mouse. Goronzy explains that the chimera model is a valid lab technique for studying human disease because it involves human tissue, with the mouse acting only as a carrier.

The researchers found in the tissue that T cells – lymphocytes that play a key role in protecting the human immune system – have trouble repairing the damaged DNA. In response, the cells activate an enzyme that induces inflammation.

The treatment calls for administering a chemical agent that restrains the enzyme and thereby improves the ability of the T cells to repair the DNA, thus reducing inflammation. The agent, ethanone, works to stop a DNA–dependent protein (DNA–PKcs) from causing apoptosis, a form of cell death. This increases the viability and diversity of naive lymphocytes in the tissue of people with rheumatoid arthritis, according to the researchers.

Goronzy says other research teams have studied the link between DNA damage and inflammation, but that his was the first to explain how the enzyme DNA–PKcs plays a role in the development of rheumatoid arthritis. Other chemicals besides ethanone can have similar effects in subduing DNA–PKcs, he adds.

The U.S. Patent and Trade Office approved ethanone as a method to boost immune function in December 2016. VA jointly owns the patent with Stanford. VA's Technology Transfer Program, which often assists VA researchers in obtaining patents, helped with the process.

The lab testing has been done at the Palo Alto VA and at Stanford. Although mice were used, Goronzy is confident the treatment will work in humans because the pathway contributing to the disease was linked to T cells from people with rheumatoid arthritis.

At the same time, Goronzy says "significant development" is needed before ethanone can enter the clinical testing phase. Any further development will depend on finding a commercial partner, he notes. It's unknown what side effects the chemical may cause, and it's too early to predict if and when the Food and Drug Administration will approve it, he says.