Lupus is a chronic autoimmune disease that can damage any part of the body, from the skin to the joints through the organs. It is a disease that acts by outbreaks and then seems to disappear before returning again.
But researchers say they have discovered that by using a combination of two drugs already exist, it is possible to reverse the effects of lupus in mice.
In a new study published in Science Translational Medicine, researchers at the University of Florida, Gainesville, have discovered that by inhibiting certain metabolic pathways in immune cells that can fight lupus in mice. Researchers at UF Health may have found a way to control lupus changing the way the immune system cells use energy.
“The most surprising result of this study was that the combination of the two metabolic inhibitors were needed to reverse the disease.” Dr. Laurence Morel, University of Florida College of Medicine
Systemic lupus erythematosus or lupus, is an autoimmune disease in which the immune system that is supposed to protect the body against foreign invaders – attacks the body’s own tissues, causing inflammation. Lupus can sometimes have symptoms similar to arthritis.
One of the markers of lupus are CD4 T cells (white blood cells that activate other immune cells). For people with lupus, the metabolism of T cells is overactive. T cells activated involve hyper- increased inflammation, and this means more physical damage. When researchers blocked glucose metabolism by using an inhibitor of glucose, metformin (common treatment in type 2 diabetes), CD4 T cells return to normal activity (metabolism CD4 slows down) and lupus symptoms were reversed. “If the T cell is normal, the disease gets better,” Morel said.
The research team initially had the idea of using a two-pronged attack on lupus after seeing a similar approach in research in cancer, said Dr. Laurence Morel, director of experimental pathology and professor of pathology, immunology and medicine laboratory in the UF College of Medicine.
“If it works to limit the metabolism of cancer cells, should work to limit metabolism in T cells,” said Dr.Morel.
The efficacy of metformin in restoring normal function of T cells when studied in the laboratory is also bode well for potential future application for the treatment of patients with lupus.
“That suggests that metabolic inhibitors can also be used to treat patients,” Morel said. “It’s the first time has shown that it can have an effect on the symptoms and manifestation of lupus by normalization of cellular metabolism.”
The two used in research in this study drugs were shown to inhibit the metabolic pathways before, but the combination seems to be the key to success.
“The most surprising result of this study was that the combination of the two metabolic inhibitors were needed to reverse the disease, when they could have predicted, based on models published by other people that one would work,” said study co-author ,
Dr.Laurence Morel, director of experimental pathology and professor of pathology, immunology and laboratory medicine at the University of Florida College of Medicine.
Among other researchers who worked on the project are: Dr. Eric S. Sobel, associate professor of rheumatology and clinical immunology professor; Dr. Byron P. Croker, a professor of renal and surgical pathology; and Dr. Todd Brusko, assistant professor in the UF Diabetes Institute, department of pathology, immunology and medical laboratory.
Their research was funded by grants from the National Institutes of Health and the Alliance for Lupus Research. The human trial will be made in September 2015, favorable results are expected since the tests in mice was a success.