AUTHOR=Nagy Nadine , Kuipers Hedwich F. , Frymoyer Adam R. , Ishak Heather D. , Bollyky Jennifer B. , Wight Thomas N. , Bollyky Paul L. TITLE=4-Methylumbelliferone Treatment and Hyaluronan Inhibition as a Therapeutic Strategy in Inflammation, Autoimmunity, and Cancer JOURNAL=Frontiers in Immunology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2015.00123 DOI=10.3389/fimmu.2015.00123 ISSN=1664-3224 ABSTRACT=

Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug in Europe and Asia called “hymecromone” where it is used to treat biliary spasm. However, there is uncertainty regarding how 4-MU treatment provides benefit in these animal models and the potential long-term consequences of HA inhibition. Here, we review what is known about how HA contributes to immune dysregulation and tumor progression. Then, we review what is known about 4-MU and hymecromone in terms of mechanism of action, pharmacokinetics, and safety. Finally, we review recent studies detailing the use of 4-MU to treat animal models of cancer and autoimmunity.