Drugs that block LTB4 bring relief to millions of patients with lymphedema

Lymphedema, also known as lymphoedema and lymphatic edema, is a condition that results from impaired flow of the lymphatic system. Patients often experience swelling in one or more extremities and pain from secondary complications, and are prone to infections. According to estimates, the condition affects as many as 140 million people worldwide, making it a global health problem. Unfortunately, there is no cure or drug therapy until now. The condition is usually managed by massage and compression garments or bandaging. It is imperative to develop novel, effective therapies.

A team led by scientists at VA Palo Alto Health Care System and Stanford University School of Medicine has found a potential therapy strategy for lymphedema. The scientists find that a protein called LTB4 could be a promising drug target for the treatment of acquired lymphedema. There are drugs available to target this protein, and these drugs could be repurposed to combat lymphedema.

Lymphedema can be inherited, but it is most frequently caused by cancer treatment. A deeper understanding of the mechanism underlying lymphedema may guide the development of therapeutics. Previous studies have shown that an anti-inflammatory drug called ketoprofen is able to reverse histopathology in experimental lymphedema. However, the drug may have a lot of side effects. In the present work, the team focused on its action against lymphedema. Using a mouse model of lymphedema, they discovered that ketoprofen reversed edema, improved lymphatic function, and restored lymphatic architecture by inhibiting the 5-lipoxygenase metabolite leukotriene B4 (LTB4). Further investigation showed that LTB4 was increased in cells from patients with lymphedema, and that LTB4 was harmful to lymphatic repair at the levels observed in established disease.

A cancer drug called bestatin also showed promise for ameliorating lymphedema. Compared to ketoprofen, bestatin can more selectively target LTB4 and has fewer side effects. The team is planning to test bestatin in humans. Relief for lymphedema patients may become a reality in the near future. (Cusabio offers LTB4 and Recombinant FGFR3.)

The study “Leukotriene B4 antagonism ameliorates experimental lymphedema” is reported 10 May 2017 in Science Translational Medicine. The first author is Wen Tian.