ARTICLE | Distillery Therapeutics

Therapeutics: Protein kinase B (AKT; AKT1; PKB; PKBA); microRNA-155 (miR-155)

September 22, 2016 7:00 AM UTC

Cell culture and mouse studies suggest inhibiting the miR-155/AKT signaling pathway could help treat a virulent subtype of leishmaniasis. In mouse bone marrow macrophages, a strain of Leishmania guyanensis that naturally harbors a virulence-enhancing RNA virus increased miR-155 levels compared with a strain of L. guyanensis that did not harbor the virus. In the macrophages infected with the virus-harboring strain of L. guyanensis, an AKT inhibitor tool compound decreased macrophage and consequent parasite survival compared with vehicle. In mice infected with the same strain of L. guyanensis, knockout of miR-155 decreased parasite burden in the footpad and tail, footpad inflammation and AKT phosphorylation in macrophages within disease lesions compared with normal miR-155 expression. Next steps could include identifying and testing miR-155 inhibitors in models of leishmaniasis...