Lupus is a chronic autoimmune disease that knows no bounds and can damage any part of the body, from the skin to the joints to the organs.
There is no cure for lupus, a disease that flares up and then seems to disappear before returning again.
But researchers say they have discovered that by using a combination of two drugs that already exist, it’s possible to reverse lupus in mice.
In a new study published in Science Translational Medicine, researchers from the University of Florida, Gainesville, have found that by inhibiting certain metabolic pathways in immune cells it’s possible to combat lupus in mice.
Each year, 16,000 new cases of lupus are reported across the country. The disease affects about 1.5 million Americans, according to the Lupus Foundation of America.
Systemic lupus erythematosus, or lupus, is an autoimmune disease in which the immune system — which is supposed to protect the body from outside invaders — attacks the body’s own tissues, causing inflammation. Lupus can sometimes have similar symptoms to arthritis.
One marker of lupus is defective helper T cells, white blood cells that activate other immune cells. These T cells eat glucose and oxygen in order to produce energy.
For people with lupus, T cell metabolism is hyper-activated. Hyper-activated T cells mean increased inflammation, and for people with lupus, that means more physical damage.
The two drugs researchers tried in the current study have been shown to inhibit metabolic pathways before, but the combination seems to be the key to success.
“The most surprising result from this study was that the combination of the two metabolic inhibitors was necessary to reverse disease, when it could have been predicted based on models published by others that either one alone would work,” said study co-author Laurence Morel, Ph.D., director of experimental pathology and a professor of pathology, immunology, and laboratory medicine in the University of Florida College of Medicine, in an email to Healthline.
How Researchers Attacked Lupus
Researchers from the University of Florida decided to look at glycolysis — the conversion of glucose into energy — and mitochondrial metabolism — energy production in the cell — as they relate to T cell metabolism.
“The two processes regulate the energy states of immune cells, which are hyper-activated in lupus and responsible for initiating and sustaining the disease,” Morel said. “Our study is the first to report a detailed analysis of these cellular metabolic pathways in lupus.”
To attack lupus, the researchers decided to use two drugs that block glycolysis and mitochondrial metabolism. The drugs are 2DG (under development) and metformin (FDA-approved).
In doing so, the researchers effectively reversed lupus in mice. They also showed that T cells from human lupus patients with enhanced glycolysis and mitochondrial metabolism saw slower cellular metabolism when they were exposed to metformin.
The two drugs did not affect T cells in healthy mice. The drugs can also be used safely and at a modest cost, the scientists say.
Researchers said it appears that by using low doses of metabolic inhibitors in the hyper-activated immune cells of lupus mice, cellular metabolism normalizes. The two drugs lower cellular metabolic activity without blocking it entirely.
“This study may also open the door to targeting other metabolic pathways,” Morel said. “In addition, such a new class of drugs may potentially benefit patients with lupus, as opposed to the more classic approach that typically relies upon immunosuppressive drugs.”
Before the drug duo can move into clinical trials, researchers need to compare the effects of the pair on human patients using it for other conditions. There is still more to be done on mice, including tests to determine whether metabolic inhibitors can be used alongside conventional lupus drugs.
The University of Florida researchers are also in the process of testing how long treatment can be stopped in mice before the disease flares up again.