Granzyme B: A novel therapeutic target in cutaneous leishmaniasis
Grantee: David Granville, Professor, University of British Columbia
Amount: DKK 2,023,506
Grant category: Research grants in open competition
Cutaneous leishmaniasis (CL) is a designated ‘WHO top-neglected tropical disease’, with up to 1 million new cases worldwide annually. CL is an inflammatory skin disease caused by infection with Leishmania parasites that leads to tissue damage, ulcers, and severe scarring, despite current treatment options.
The goal of this project is to provide a key rationale for pursuing Granzyme B (GzmB) as a novel therapeutic target for the treatment of cutaneous leishmaniasis.
GzmB is a protein that is aberrantly elevated in CL lesions and other inflammatory skin conditions. GzmB activity has been demonstrated to cleave important proteins in the skin, thereby worsening tissue damage, delaying wound healing, and causing scarring in inflammatory patient skin specimens and in experimental models. Importantly, inhibition of GzmB has shown efficacy in delaying these disease phenotypes.
Using lesional specimens from CL patients, a well-established experimental model, and a GzmB inhibitor, the contributions of GzmB to inflammation, impaired wound healing, and scarring in CL will be delineated in this study.