August 15, 2024 | In recent months, Diagnostics World has taken a look at new developments taking place in the field of sarcoidosis research, including progress made toward a simple blood test and new treatment options as well as efforts to gain a better understanding of cardiac sarcoidosis in particular. Here, we explore the role of philanthropic funding, highlight research projects and collaborative initiatives, and sum up efforts to improve clinical trial diversity.
Role of Philanthropic Funding
According to Quinton Banks, associate director at the Milken Institute’s SPARC (Science Philanthropy Accelerator for Research and Collaboration), financial support for sarcoidosis is low compared to other conditions for a variety of reasons. He told Diagnostics World that philanthropic funding in this field is crucial because it can be more adaptable than other forms of support. It can also be deployed quickly, he added, enabling those carrying out the research to start exploring their ideas and areas of interest as soon as possible.
“One of the main goals of philanthropic funding in this space is to build the research community and provide a scientific foundation for others to build on,” he said. “By supporting studies in sarcoidosis fundamental biology, philanthropy is supporting work that could be utilized to imagine, develop, and test life-saving diagnostics and therapeutics for all those who are currently living with sarcoidosis.”
The disease remains “relatively unknown and poorly understood,” he explained, which can lead to misdiagnoses and reduced quality of life for those dealing with potentially debilitating symptoms. Meanwhile, treatment options remain limited for those who have been diagnosed. To address these types of issues, the Ann Theodore Foundation (ATF) and the Milken SPARC team launched the Ann Theodore Foundation Breakthrough Sarcoidosis Initiative (ATF-BSI) in recent years.
The intent is to support research and identify critical areas for investment that could help gather a better understanding of this disease and accelerate the development of new therapies. “ATF-BSI seeks to help investigators gather preliminary data or test innovative ideas that could receive follow-on support from governmental grants,” Banks noted in an editorial piece published in the American Journal of Physiology-Lung Cellular and Molecular Physiology (DOI: 10.1152/ajplung.00084.2024).
Banks indicated that the field has made progress over the last several years and that “there is forward momentum in the field.” Novel therapeutics designed to treat sarcoidosis are now in clinical trials, for example. And although research devoted to this disease has traditionally been limited, it does seem to be on the rise. For example, he noted that annual NIH financial support has grown by over 25% in the last three years.
Still, there is more to learn and more to be done, and the ATF-backed research projects, “have the potential to create impactful clinical tools and lay the groundwork for therapeutic discoveries in the long term,” he wrote. “Understanding the underlying biology of sarcoidosis now is our best bet to catalyze new research in the future, which can lead to more robust research, new interventions, and hope for patients.”
Current and Forthcoming Research Projects
ATF-BSI supports several research groups in the United States and Europe that are exploring the disease’s underlying biology, developing resources for the research community, and creating clinical tools that could potentially benefit patients. Some grantees are pursuing models focused on disease progression or the risk of severe outcomes, others are pursuing molecular pathways, and still others are aiming to understand how granulomas form or why they persist.
One example is Alejandro Pezzulo, an associate professor of Pulmonary and Critical Care Medicine at the University of Iowa’s Carver College of Medicine. “Our project aims to determine whether the epithelial cells that line the airways of the lungs of people with sarcoidosis have abnormal responses to microorganisms that have been epidemiologically linked to the disease,” he told Diagnostics World.
“Any abnormal responses may determine how the immune system and the rest of the body respond and result in the formation of granulomas,” he added.
Pezzulo said the “end goal is very relevant for diagnostics.” He and colleagues intend to validate whether their findings have diagnostic value by exploring whether epithelial abnormal responses are sensitive and specific to sarcoidosis, for example, and by learning how they can potentially be detected early on in the disease. From there, they hope to work with industry “to develop a simplified subject cell-based assay to diagnose the disease.”
Lindsay Celada, an immunologist at Baylor College of Medicine, is another one of the grant-funded researchers. She is exploring the role of a subset of adaptive immune cells in progressive fibrotic sarcoidosis. Proteins can potentially inhibit other proteins, Celada explained, and a phosphatase called SHP2 is highly active in sarcoidosis CD8+ T cells.
The high activity of this phosphatase prevents the degradation of another protein called TBET. “If you don’t have degradation of this other protein called TBET, then it leads to the overproduction of a pro-inflammatory cytokine called interferon‐gamma (IFN‐γ),” she told Diagnostics World, “and high levels of IFN‐γ, in turn, can cause tissue damage.”
In a paper published in Science Translational Medicine (DOI: 10.1126/scitranslmed.ade2581), Celada and colleagues demonstrated that high levels of IFN‐γ lead to high levels of collagen, which is involved in fibrosis. She explained that the first part of their grant-funded work is examining that pathway.
The researchers have also found that in mice with sarcoidosis-like disease, some responded to an inhibitor of SHP2 called SHP099, and other mice did not respond to the treatment. The second part of the grant-funded work proposes that a specific cell contributes to the differences observed in these mice. Celada said her main long-term goal is to develop an effective treatment option for fibrotic sarcoidosis.
Addressing Disparities, Improving Clinical Trial Diversity
“Sarcoidosis is a disease of disparities,” Mary McGowan, CEO of the Foundation for Sarcoidosis Research (FSR), told Diagnostics World, and “we’re doing a lot of work in this area.” Black Americans, and Black American women in particular, have a higher incidence of sarcoidosis and poorer outcomes compared to other groups.
According to FSR, Black Americans are more than twice as likely to have sarcoidosis than White Americans, in addition to experiencing more severe and chronic forms of the disease, worse health outcomes, and higher hospitalization and mortality rates than other groups. Although systemic issues likely contribute to these outcomes, further research is needed to understand why this disease impacts the Black community differently.
McGowan emphasized the importance of ensuring a clear understanding of how sarcoidosis—and other rare and chronic diseases—impact different communities and populations in order to achieve better patient outcomes for everyone. One significant challenge, however, involves the level of enrollment in clinical research.
FSR notes that Black Americans represent less than 1 in 10 clinical trial participants for rare diseases and indicates that this lack of inclusivity reduces the applicability of findings to all groups, especially those most severely impacted by this disease. Improving the representation of Black Americans in clinical trials could help lead to more comprehensive data and better protocols, treatments, and outcomes for all sarcoidosis patients.
It’s become one area of focus for FSR through a campaign called Ignore No More. In 2021, the Foundation announced the first phase of this campaign to raise awareness of the disproportionate impact the disease has on Black American women in particular.
The following phase, launched in 2022 and called the Ignore No More: ACTe Now! (Advance Clinical Trials for Equity in Sarcoidosis) campaign, sought to identify issues that lead to lower clinical trial participation, offer recommendations for a more inclusive recruitment approach, and improve the representation of Black Americans in sarcoidosis research.
In May of this year, FSR announced the start of the Coalition for Clinical Trial Equity as part of the latest phase of Ignore No More. FSR initiated a search for individuals and organizations committed to finding and implementing solutions to address barriers to clinical trial diversity. The result is a 26-member Steering Committee comprising various stakeholders such as patients, patient advocacy organizations, clinicians, medical societies, and industry.
Collaborative Initiatives, Upcoming Event
At this point, FSR has doled out over $6 million in research funds. Part of these efforts involves the search for key biomarkers for diagnosis, McGowan explained, and another significant push involves the search for biomarkers that can indicate why the disease becomes more aggressive for some patients but not for others. (Diagnostics World has covered some of these efforts, such as a blood test pursued by Wayne State University researchers and cardiac sarcoidosis explorations underway at Johns Hopkins University.)
In addition to these types of individual grant-funded research projects, McGowan highlighted an FSR organizational undertaking called the Global Sarcoidosis Clinic Alliance. It is a member program made up of hospitals and clinics across the globe, in addition to individual patients, providers, and caregivers. One of its primary purposes is to ensure patients have access to information, education, support services, and clinical trials. Additional aims include supporting clinicians and accelerating research.
In just two years, McGowan indicated that over 40 member hospitals are now involved, and she encouraged other institutions to consider joining this worldwide network of sarcoidosis clinics. Through clinician education, best practice sharing, and standardization of clinical practice powered by this new alliance, “we believe we will be able to improve sarcoidosis diagnosis in the very near future,” she said.
Beyond the Clinic Alliance, McGowan pointed out that FSR has formed strategic partnerships with other groups, such as the Open Source Imaging Consortium (OSIC), to explore whether AI can play a role in helping better identify possible cases of sarcoidosis in standard imaging. According to OSIC, the effort includes industry, academia, and patient advocacy groups and brings together experts such as clinicians, computational scientists, and radiologists to “advance digital imaging biomarkers for accurate imaging-based diagnosis, prognosis, and prediction of response to therapy.”
Looking ahead, McGowan said FSR plans to host an externally led patient-focused drug development meeting on October 28. The virtual event is meant to give patients and caregivers the chance to share thoughts about aspects like quality-of-life issues tied to this disease as well as unmet needs and preferences regarding symptom management. She anticipates there will also be discussion on how to improve diagnosis.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.