LRRK2 Inhibitors: Novel Treatment for Intestinal Bowel Disorders

Use of Leucine Rich Repeat Kinase 2 (LRRK2) inhibitors for the treatment of Intestinal Bowel Disorders (IBD) is disclosed. IBD is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract. Crohn's disease and ulcerative colitis, two common forms of idiopathic IBD, are chronic, relapsing inflammatory disorders of the gastrointestinal tract.

LRRK2 is a kinase encoded by a gene that contains a non-coding polymorphism (SNP). LRRK2 has been associated with and is a risk factor for inflammatory bowel disease. NIH inventors have shown that human cells expressing this SNP have increased levels of LRRK2 and, correspondingly, mice with increased levels of LRRK2 exhibit more severe Dextran Sulfate colitis. In various studies of the role of LRRK2 in cell signaling, NIH inventors have shown that increased levels of LRRK2 lead to increased pro-inflammatory cytokine secretion. Also, an inhibitor of LRRK2 is shown to abrogate the pro-inflammatory activity of LRRK2 both in vitro and in vivo.