LRA Funds Research Projects to Find New Therapies for Lupus
The award recipients presented their findings at the recent 13th International Congress on Systematic Lupus Erythematosus (LUPUS 2019), in San Francisco, California.
One of the projects, led by Mariana Kaplan, MD, from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), was presented at the congress by Hege Pedersen, PhD, in a poster, “Treating Lupus-prone Mice with a Coenzyme Q10 Analog Decreases Disease Parameters Indicating a Therapeutic Role in Systemic Lupus Erythematosus.”
The project aims to evaluate the therapeutic potential of idebenone, originally developed to treat Alzheimer’s disease, in lupus patients. Idebenone is an artificial compound that mimics the activity of Coenzyme Q10 (also known as ubiquinone), a powerful antioxidant molecule essential for energy production mediated by mitochondria.
According to their findings, animal models of lupus treated with idebenone survived longer and showed fewer signs of kidney damage and mitochondria dysfunction normally associated with disease progression. Future clinical trials are warranted to assess the therapeutic potential of idebenone in lupus patients.
Roberto Caricchio, MD, from the Lewis Katz School of Medicine at Temple University, led and presented another funded project in a poster, “Bacterial Biofilm Product Curli/edna Induces Nets and Serum Anti-curli/edna Levels Correlate with Bacteriuria and Lupus Activity.”
This project first aims to investigate whether there is a relationship between bacteria that cause urinary tract infections and lupus flare-ups; and secondly, whether antibiotics might be useful to prevent lupus flare-ups.
According to their findings, in a mouse model of lupus, disease symptoms may worsen because of the presence of small protein fibers called curli, which are released by bacteria that normally cause urinary tract infections. This happens because animals start producing antibodies against curli, triggering a strong immune response that may also aggravate lupus symptoms.
The team found these anti-curli antibodies are also present at high levels in blood samples from lupus patients, especially in those experiencing disease flare-ups. The group is now hopeful that standard antibiotics used to eliminate bacteria that cause urinary tract infections may one day be used to prevent lupus flare-ups.
Another project, led by Deepak Rao, MD, PhD, from the Harvard Medical School, was presented by Celine Berthier, PhD, in a poster, “The Immune Cell Landscape in Kidneys of Lupus Nephritis Patients.”
The project is part of the Accelerating Medicines Partnership (AMP) co-sponsored by the LRA, and aims to identify new diagnostic and therapeutic targets for lupus nephritis, an inflammation of the kidneys caused by lupus.
In the study, researchers are examining the profile of immune cells that infiltrate the kidneys and cause inflammation in hopes of finding new therapeutic targets to control the disease. So far, they have identified three types of T cells in the kidneys of lupus nephritis patients. Now the team is trying to understand the specific contribution of each of these immune cells to the condition.
Another project, led by Theresa Lu, MD, PhD, from the Hospital for Special Surgery Research Institute, was presented by Noa Schwartz, MD, MS, in a poster, “Dermal Lymphatic Characterization in the MRL/lpr Lupus Model.”
The project aims to understand how lupus changes the lymphatic system — the vessels that transport lymphatic fluid and immune cells in and out of tissues.
According to their findings, in mice with lupus, the circulation of fluid and immune cells in the lymphatic system is reduced to the point that inflammatory molecules produced by immune cells become “trapped” in the tissue, worsening skin inflammation. The team is convinced that a similar mechanism may be responsible for severe skin inflammation in some lupus patients.