image: Skin fibroblasts isolated from a scleroderma patient. The red fluorescence is staining alpha-smooth muscle actin, a myofibroblast marker usually seen in high levels in these patients. These activated cells are the culprit in scleroderma fibrosis.view more
Credit: Michigan Medicine
More than 50 million Americans are affected by an autoimmune disease, with women at an increased risk for developing one.
“As a National Institutes of Health Autoimmunity Center of Excellence site, we have the opportunity at Michigan Medicine to conduct extensive translational research, in a clinical trial setting, on autoimmune diseases which allows us to provide the newest, targeted and personalized therapies to our patients.”
Khanna and his fellow rheumatology colleagues, J. Michelle Kahlenberg, M.D., Ph.D., and David Fox, M.D., were awarded a grant, up to $10.2 million, by the Autoimmunity Centers of Excellence to explore three new projects for potential treatments of autoimmune diseases.
“I will be leading the project on scleroderma, Dr. Kahlenberg will lead a project on lupus and Dr. Fox will lead a collaborative project where we will study a broad range of other autoimmune diseases,” says Khanna, who is a co-principal investigator of the grant with Fox.
New projects
While new treatments for autoimmune conditions may help patients with some of their symptoms, they often lead to impairment of normal immune system functions, leaving many patients more susceptible to infections. The research team will study how molecular targets affect autoimmune inflammation and damage, and how to avoid impairing the immune system’s ability to fight infection.
In the scleroderma project, Khanna will test the drug elotuzumab, already approved by the U.S. Food and Drug Administration for treatment of the blood cancer multiple myeloma, as a potential treatment for patients with scleroderma.
“The trial design will recruit patients with early scleroderma who have elevated levels of abnormal lymphocytes, CD4+ cytotoxic T cells, in the blood,” Khanna says. “The project will be a safety trial, and we hope it can open a new treatment option for patients affected with scleroderma, a disease without FDA approved therapies.”
In the lupus project, Kahlenberg, an associate professor of rheumatology, will test the drug, tofacitinib, currently approved to treat rheumatoid and psoriatic arthritis, in cutaneous lupus.
Lupus is an autoimmune disease where the body’s immune system attacks its own tissues and organs. Those affected experience inflammation throughout the body, as well as fatigue.
She has previously studied a signaling protein tied to UV light sensitivity in patients with lupus. This project will build upon that work and provide further proof that blocking the protein’s pathway can provide protection from UV light. Kahlenberg will also study the role tofacitinib plays in the protein signaling.
“We’re hoping to provide more targeted and less toxic therapies for our lupus patients,” she says.
In the final project, Fox will explore new molecular targets in a range of autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, lupus, scleroderma and autoimmune eye diseases.
“This project will be an opportunity to take new discoveries related to rheumatoid arthritis and apply this progress to the study of many other autoimmune diseases that affect multiple organs and tissues in our patients, with the ultimate goal of safer and more effective treatment,” Fox says.
Future results
The researchers are excited for the projects to get underway and hope to have results in the next three to five years.
“We’re constantly exploring new treatment options for our patients with autoimmune diseases,” Khanna says.
“Grants, such as this one, help us take our work from the lab and translate it into tangible benefits for the patients we see each day in clinic.”
This work will be performed under the University of Michigan Clinical Autoimmunity Center of Excellence, grant number AWD012101, funded by the NIH-NIAID.
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