title: 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer.
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.
authors: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, CA , USA.
authors: Nadine
authors: N
authors: Nagy
authors: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, CA , USA.
authors: Hedwich F
authors: HF
authors: Kuipers
authors: Department of Pediatrics, Stanford University School of Medicine , Stanford, CA , USA.
authors: Adam R
authors: AR
authors: Frymoyer
authors: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, CA , USA.
authors: Heather D
authors: HD
authors: Ishak
authors: Department of Pediatrics and Systems Medicine, Stanford University School of Medicine , Stanford, CA , USA.
authors: Jennifer B
authors: JB
authors: Bollyky
authors: Matrix Biology Program, Benaroya Research Institute , Seattle, WA , USA.
authors: Thomas N
authors: TN
authors: Wight
authors: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, CA , USA.
authors: Paul L
authors: PL
authors: Bollyky
keywords: 4-methylumbelliferone; cancer; hyaluronan; hymecromone; immune diseases