LRA is Unraveling Lupus Heterogeneity to Turn Complexity to Cure
LRA is Unraveling Lupus Heterogeneity to Turn Complexity to Cure

July 22, 2021

Why is lupus so tough to treat? Why is it so difficult to test possible new treatments in a clinical trial? Why are so many people needed for a clinical trial to prove effectiveness? And how does LRA intend to Turn Lupus Complexity to Cure?

The answers lie at the core of lupus – its heterogeneity – the fact that it affects each person differently and symptoms fluctuate even within the same person.  While one woman may have joint pain and fatigue, another may have those symptoms along with skin rashes, fevers and high blood pressure. And for her dad, symptoms may come and go with permanent damage to his kidneys. This heterogeneity means that certain treatments may only work for particular patients—one treatment is unlikely to be effective for such a variety of symptoms and causes. Knowing more about, the disease’s diversity will allow researchers to design new drugs that target specific groups of patients.

Identifying Heterogeneity
With an LRA grant, in 2008, the leading lupus researcher Dr. Virginia Pascual and her colleagues set the stage for understanding the diversity of the disease by introducing a new approach  investigating how the immune system works in patients with lupus that involved analyzing the activity of different genes. Dr. Pascual and her team took the results further in a groundbreaking 2016 study in which they identified which genes were active in blood samples from 158 children with lupus. They determined that based on these genes, patients could be separated into seven groups. This findingmay enable scientists to tailor treatments for each group. Dr. Pascual then received the 2017 Lupus Insight Prize from the LRA that allows her to further investigate lupus heterogeneity. We will keep you posted on these results.

How Understanding Heterogeneity Will Advance Treatment
Meanwhile, LRA’s research grants are supporting new work using the very latest technology to identify distinct and shared pathways that control cells and cause disease in people with lupus. And our funded researchers are working on identifying several novel biomarkers for lupus – substances in the body that suggest the presence of disease. Knowing these markers for lupus, which likely vary from person to person, may simplify the interpretation of data from clinical trials and will eventually help in diagnosing and monitoring the disease activity.

With a network of 57 prestigious academic clinical research centers, the LRA’s affiliate Lupus Therapeutics will support the discovery and development of novel disease pathways and targets to optimize treatments. Importantly, linking targets to patient heterogeneity to stratify people with lupus will promote personalized treatments and successful clinical trials. An essential element to achieve this priority will be encouraging diverse populations to participate in lupus trials, particularly African American women who are disproportionately affected by lupus. Further, the development of new endpoint measures – ways to measure the success of experimental medicines – is urgently needed. LRA will focus aggressively on the development of these endpoints as well.

“At the end of the day, the best thing we can do for anyone living with lupus is to unravel the complexities of this highly individualized disease because that is what will lead to new breakthroughs and new treatments,” said Kenneth M. Farber, President and CEO of the LRA. “The Lupus Research Alliance has been responsible for many of the developments that have led to recent scientific advancements and potential treatments. We are at a turning point in research where through precision medicine we can focus on heterogeneity and novel pathways to increase our understanding of lupus, which will allow us to advance lupus research and treatment even further.”

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