ARPA-H Funds Columbia Researchers to Accelerate Diagnosis of Rare Lymphatic Diseases

A team of researchers at Columbia University Vagelos College of Physicians and Surgeons has been awarded up to $8.7 million from the Advanced Research Projects Agency for Health (ARPA-H) to develop faster and more accurate genetic tests for congenital defects in the lymphatic system. This initiative aims to significantly reduce diagnostic delays and improve treatment outcomes for patients born with these rare and often life-threatening conditions.

Understanding the Lymphatic System

The lymphatic system, often referred to as the “forgotten circulation,” is a crucial network of vessels, ducts, and nodes responsible for maintaining fluid balance, transporting immune cells, and removing waste throughout the body. Although many are familiar with lymph nodes and their role in fighting infection, the broader lymphatic system is less understood.

The Challenge of Congenital Lymphatic Diseases

Congenital lymphatic diseases arise from genetic defects that disrupt the normal function of the lymphatic system. These defects can lead to a range of severe health problems, including breathing difficulties due to fluid buildup in the lungs and increased susceptibility to life-threatening infections like sepsis. Approximately one in every 3,500 babies is born with a lymphatic defect, often requiring immediate intensive care.

As the disease progresses, abnormal lymphatic growth can damage organs, particularly the spleen, heart, and lungs, ultimately leading to organ failure.

The CLARUM Project: A Collaborative Effort

The project, known as CLARUM (Comprehensive Lymphatic Anomaly Revealing and Understanding Genomics), is a collaborative effort involving researchers from Columbia University, Arkansas Children’s Hospital, Boston Children’s Hospital, the Broad Institute, Children’s Hospital of Philadelphia (CHOP), City St. George’s University of London, and NYU Langone Health.

CLARUM aims to identify genetic mutations responsible for lymphatic anomalies and translate these findings into widely accessible clinical tests. Currently, diagnosis can be delayed due to the complexity of the diseases and limited access to specialized genetic testing, with an estimated 80% of cases potentially undiagnosed.

Accelerating Diagnosis and Improving Treatment

The funding for CLARUM comes from the ARPA-H LIGHT (Lymphatic Imaging, Genomics, and pHenotyping Technologies) program, which focuses on improving the understanding and treatment of lymphatic disorders.

Researchers anticipate discovering 15 or more new genetic mutations linked to lymphatic disease, enhancing the predictive value of genetic testing. Identifying these genetic causes is crucial, as targeted therapies are available for approximately 20-30% of patients with lymphatic anomalies caused by specific mutations. The team plans to develop two genetic tests within two years, utilizing standard clinical specimens to detect both germline and mosaic mutations in 73 genes associated with primary lymphatic anomalies.

Future Outlook

“Discovering genes that cause lymphatic anomalies and using this information to create new clinical tests will not only accelerate the diagnosis of patients, but will too lead to improved treatments and, most importantly, save lives,” says Carrie Shawber, PhD, associate professor of reproductive sciences at VP&S and principal investigator of the CLARUM project. The CLARUM project represents a significant step towards improving the lives of individuals affected by these rare and challenging conditions.