1021 GMT March 31, 2020
In a study published in the US journal Science Translational Medicine, researchers also described how a drug in clinical development reversed lymphedema complications, which potentially paves the way to safe and effective therapies for the currently untreatable condition, according to news.xinhuanet.com.
Study co-senior author Stanley Rockson, professor of cardiovascular medicine at Stanford University, said, "We figured out that the biology behind what has been historically deemed the irreversible process of lymphedema is, in fact, reversible if you can turn the molecular machinery around.”
Lymphedema is a progressive disease that causes debilitating pain and swelling in roughly 15 to 50 percent of cancer survivors, and an estimated 90 million individuals around the world struggle with the condition — as a result of radiation therapy or parasitic worm infections.
Addressing lymphedema with compression garments cannot prevent tissue damage, and although a clinical trial is underway to evaluate an anti-inflammatory drug called ketoprofen, use of the compound comes with significant side effects for the liver, gut, heart, and nervous system.
In the new study, the researchers found that the buildup of lymph fluid is actually an inflammatory response within the tissue of the skin, not merely a ‘plumbing’ problem within the lymphatic system, as previously thought.
A naturally occurring inflammatory substance known as leukotriene B4, or LTB4, was then found elevated in both animal models of lymphedema and in humans with the disease.
And at elevated levels, LTB4 can cause tissue inflammation and impaired lymphatic function.
Further research in mice showed that by using pharmacological agents to target LTB4, the scientists were able to induce lymphatic repair and reversal of the disease processes.
Based on results of the study, a drug called bestatin, which is not approved for use in the US but which has been used for decades in Japan to treat cancer, was found to work well as an LTB4 inhibitor, with no side effects.
What's more, a clinical trial to evaluate bestatin for treating lymphedema began in May 2016.
The study said, "LTB4 antagonism may thus represent a promising approach in a disease that is currently in need of medical therapies.
"There is a significant unmet medical need for pharmacologic interventions for this common, serious, and life-altering disease.
“Enhanced mechanistic insights into the ways in which unchecked inflammation contributes to lymphatic pathology should facilitate new therapeutic discoveries."