A new hope for lymphedema treatment
An innovative strategy to treat lymphedema has been discovered by the research team coordinated by Professor Agnès Noel in the GIGA Institute (Laboratory of Biology of Tumor and Development, Investigators of WELBIO-Walloon Excellence in Life Science and Biotechnology). Lymphedema is a chronic condition that causes painful swelling, usually in the arms or legs. Their groundbreaking findings, published in a leading vascular biology journal (Circulation) have identified a key molecular target and proposed a new therapy that has shown promising results in a pre-clinical model.
Lymphedema results from dysfunction of the lymphatic system leading to fluid accumulation, swelling (edema), inflammation, and important tissue changes, which can lead to pain and reduced mobility. It often occurs after surgery, radiation therapy (especially in cancer treatment), infections, or injury. This condition can cause discomfort, reduced mobility, and has a significant impact on the quality of life.
At the heart of the discovery is a membrane receptor called uPARAP, which plays a crucial role in the formation of lymphatic vessels. The researchers explored how this molecule influences the development of a lymphatic network and its ability to drain excess fluid.
“Surprisingly, we found that a more complex “labyrinth-like” lymphatic network with branched and twisted vessels attenuated lymphedema”, says Agnès Noel. By integrating advanced assays and mathematical modeling, they showed that targeting uPARAP disrupted specific cell-cell connections, thereby improving draining capacity. In a pre-clinical model, removing uPARAP from lymphatic endothelial cells significantly reduced limb swelling and improved other signs of lymphedema such as skin thickening and fat deposition.
“Building on this discovery, we decided to design a cutting-edge gapmer-based therapy to block uPARAP mRNA, preventing protein production”, explains Agnès Noel. This approach successfully promoted the formation of this specialized “labyrinth-like” network and alleviated multiple symptoms of lymphedema.
This breakthrough opens new possibilities for treating lymphedema. The next steps will focus on optimizing the therapy to maximalize its efficacy and security before developing a clinical trial to assess its effectiveness in patients with lymphedema.
Reference
Targeting uPARAP Modifies Lymphatic Vessel Architecture and Attenuates Lymphedema.
Gucciardo F, Lebeau A, Pirson S, Buntinx F, Ivanova E, Blacher S, Brouillard P, Deroye J, Baudin L, Pirnay A, Morfoisse F, Villette C, Nizet C, Lallemand F, Munaut C, Alitalo K, Geris L, Vikkula M, Gautier-Isola M, Noel A.
Circulation. 2025 Mar 4. doi: 10.1161/CIRCULATIONAHA.124.072093. Online ahead of print. PMID: 40035133
