Dr. Eric Morand Publishes Results Funded by LRA’s Distinguished Innovator Award
NEW YORK, NY. March 31. Results of critical work funded by the Lupus Research Alliance Distinguished Innovator Award to Dr. Eric Morand suggests a path toward making lupus treatment with glucocorticoids (steroids) effective at lower doses, lessening harmful side effects.
In a study just published in Lancet Rheumatology, Dr. Morand (with first author rheumatology fellow. Dr. Melissa Northcott) reports identifying a group of biological markers that can indicate how much steroid lupus patients have been exposed to, since the amount that is active in the body is more important than the amount taken. The paper further shows that high activity of proteins made by the immune system, called interferons, can block the effects of steroid treatment, which means higher doses are needed to be effective.
Morand’s Results Fulfill Goal of Distinguished Innovator Award
The Distinguished Innovator Award is one of LRA’s largest and most prestigious, giving researchers up to $1 million for up to four years. Research conducted under this grant mechanism is expected to be highly innovative and to address the root causes of systemic lupus erythematosus (SLE) that can provide new directions towards a cure.
Possible Steroid Resistance in Lupus
Almost 80% of people with lupus are treated with steroids. Yet there is currently no consensus on how much of the drug to give to each lupus patient to maximize efficacy while minimizing side effects. Dr. Morand thought that it would be valuable to have a way to track patient exposure to steroids in order to maximize safety and efficacy. His research team discovered five genes that indicate a high level of steroid in the body.
People with lupus are often treated with higher doses of steroids than people with other autoimmune disorders, but they are not always effective. Dr. Morand hypothesized that lupus patients may have a degree of resistance to steroids, possibly because these patients often have high levels of type I interferon. His suspicions were borne out by his work; he found that high levels of type I interferon prevented the steroids from switching on these genes—but conversely, steroids did not block interferon’s effects on gene expression. People with high type I interferon also had a higher level of disease activity.
Blocking Type I Interferon as a Treatment Approach
These data suggest a mechanism by which type I interferon might cause steroid resistance in people with lupus. His results also suggest that targeting the interferon pathway with drugs that block its function might allow steroids to be more effective in this population and therefore work at a lower dose.
“In summary,” said Dr. Morand, “this work confirms that steroid resistance in lupus is a real phenomenon and interferons have a major effect in blocking their effects. This work would not have been possible without the support of the LRA’s Distinguished Innovator Award”
An accompanying editorial comment from the Lancet Rheumatology underscores the potential value of the study in suggesting a way to guide treatment with steroids for lupus and affirms Dr. Morand’s conclusion that additional research is warranted.
Lupus Research Alliance Chief Scientific Officer Dr. Teodora Staeva congratulated Dr. Morand’s team, noting: “High steroid use is a major issue for people with lupus, often causing long-term organ damage and numerous other side effects. These findings point to a potential approach to guide glucocorticoid treatment and cut down on their use which could make a significant difference in how patients fare over time.”
Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. More than 90 percent of people with lupus are women; lupus most often strikes during the childbearing years of 15-45. African Americans, Latinx, Asians and Native Americans are two to three times at greater risk than Caucasians. In lupus, the immune system, which is designed to protect against infection, creates antibodies that can attack any part of the body including the kidneys, brain, heart, lungs, blood, skin, and joints.
About the Lupus Research Alliance
The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance’s Board of Directors funds all administrative and fundraising costs, 100% of all donations goes to support lupus research programs.