UT Health Science Center at San Antonio’s Dr. Paolo Casali, M.D. was awarded a three-year, $600,000 Grant from The Alliance for Lupus Research for his work on the effects of drugs called epigenetic modulators in lupus.
Casali’s work focuses on immune system abnormalities that occur in systemic lupus erythematosis (SLE), an autoimmune disease. “Our team of investigators has conducted basic science research that has found an immediate translational relevance to a disease, lupus,” Dr. Casali said. “For the first time, mechanisms important to the generation of autoantibodies (the antibodies that attack components of the body) have been identified. We outlined the mechanisms and then looked for drugs that may alter them.”
The researchers were able to observe why the epigenetic modulators, often used in the treatment of lymphomas, may be useful for lupus and effective in humans.
The studies focused on two enzymes, the activation-induced cytidine deaminase (AID), a call-switch recombination and somatic hypermutation, and B lymphocyte-induced maturation protein-1 (Blimp-1), which helps the infection-fighting cells B lymphocytes to distinguish antibody-secreting cells.
Both enzymes were analyzed in a lupus mouse model. As the enzymes were reduced, a decrease in autoimmunity resulted in an overall improvement of health. Casali also observed the role of the estrogen hormone and the microRNAs’ epigenetic factors in the enzymes’ expression.
“In the Alliance for Lupus Research grant, we will systematically test the ability of different epigenetic modulators to blunt the lupus autoantibody response and ‘prevent/cure’ the disease,” Dr. Casali said. This grant complements and expands the scope of two additional and larger National Institutes of Health research grants that Dr. Casali holds to address the basic molecular and cellular mechanisms of the antibody response in health and disease.
The funding will also be used to identify novel targets for new lupus therapeutics. SLE debilitates between 500,000 and 1.5 million people in the United States, and most of the patients are women in their fertile years.
The immune system functions by defending the body against viruses, bacteria, parasites and other threats like tumors. However, with Lupus, the system turns the body against itself and its tissues, kidneys, lungs, heart, skin, brain or central nervous system. “It’s a generalized attack that systematically destroys the inner core of most cells of the body, including the DNA itself and other constituents of the cellular nuclei,” explained Casali.
Paolo Casali is not only Chairman of the Department of Microbiology and Immunology at the UTHSC San Antonio and holder of the Zachry Foundation Distinguished Chair in Microbiology and Immunology, but also a prominent immunologist, known for his work on the body’s response to viruses, bacteria, cancer cells, and tissue and organ damage in autoimmune diseases.