Chandra Mohan, Hugh Roy and Lillie Cranz Cullen Endowed Professor of biomedical engineering at the University of Houston Cullen College of Engineering, and his group have recent findings that raise optimism for a novel, more natural, therapeutic in lupus. In the most recent issue of Arthritis & Rheumatology, Mohan published an article outlining the use of a plant-derived chemical for the treatment of lupus in mice – with very promising results.
In the U.S. alone, more than 1.5 million people have lupus, a chronic autoimmune disease in which the immune system turns against itself, attacking a person’s healthy tissue, cells and organs. The symptoms can range from debilitating pain and fatigue to organ failure.
One of the most common organs to be attacked by lupus is the kidney, manifesting in lupus nephritis. An estimated 40 percent of lupus patients develop this condition, which causes inflammation of the kidneys, impairing their ability to get rid of waste products and other toxins from the body effectively. Lupus nephritis is the leading cause of lupus-related deaths and results in tens of thousands of hospitalizations per year.
Despite the high toll of this disease, there’s only been one drug approved for the treatment of lupus in the past 50 years. Lupus patients are commonly treated with steroids, a class of immunosuppressive drugs which delay the development of lupus by suppressing the patient’s entire immune system. By suppressing the immune system in its entirety, some lupus patients are able to slow down the development and progression of the disease – but at the risk of increased infections and other uncomfortable side effects.
The new findings by the Mohan group raise hope of a new class of drugs for the treatment of lupus – one which may not include a long list of adverse risks and side effects. Mohan’s article in Arthritis & Rheumatology, titled “Targeting multiple signaling axes and oxidative stress using a synthetic triterpenoid prevents murine lupus nephritis,” details the use of a synthetic, plant-derived compound – abbreviated as “CDDO” – which was shown to effectively suppress the multiple steps of lupus development in mouse models, including the onset of kidney disease.
The development of lupus has two main steps. First, the immune system develops antibodies which attack the body’s own DNA. The next step is the development of lupus-related kidney disease, or lupus nephritis. “It’s a two-step reaction: the immune system is activated, then the activated immune system attacks the kidneys,” Mohan said. “We found that CDDO may block both of these steps.”
Although these results are extremely exciting, Mohan explained there is much left to be discovered about CDDO – including how it works in suppressing the progression of lupus. The next step for this research, Mohan said, is to confirm whether the CDDO compound is generally immunosuppressive – that is, whether it suppresses the immune system across the board, thereby suppressing the development of autoimmune diseases such as lupus, or whether it simply suppresses the activation of the specific signaling pathways that lead to the development of lupus.
In order to find whether CDDO is a generallyimmunosuppressive drug, Mohan’s group will administer the compound to mice to see if they can mount the proper immune response. If not, Mohan said the compound could likely be suppressing the entire immune system, which is the current problem with using steroids to delay the progression of lupus.
However, Mohan pointed out that even if the compound is shown to be immunosuppressive, it may still be a better treatment option than steroids for some lupus patients. “The most exciting part of this research for us is that the synthetic compound is originally plant-derived, so it’s relatively natural and carries less chance of side effects,” Mohan said. “That’s a very important point because many of the current therapeutic agents being used for lupus have significant side effects. In these experiments we found that the CDDO compound had no known side effects as far as we have tested.”
“Compared to many other test compounds we’ve tried previously for treating lupus, this one appears to be much more effective, so we’re very excited,” Mohan said. However, he emphasized that this research still has a long road to travel before the drug can be added to the treatment arsenal for lupus. “To put it into perspective, it will take time to validate this before we can move on to test the compound in humans. But the idea of treating lupus patients with more natural compounds that have fewer side effects is very exciting.”