Striving to develop and implement culturally sensitive dermatologic care with the focus on eczema and psoriasis in the Cree Territory of James Bay (Eeyou Istchee)

Grantee: Ivan Litvinov, Associate Professor, McGill University Health Centre

Amount: DKK 3,074,290

Grant category: Research Grants in open competition

Year: 2023

Geography: Canada

Ivan Litvinov’s project aims to co-create with Indigenous partners and implement a culturally sensitive dermatological care system in the Cree territories in Quebec, one of Canada’s First Nations. Dermatologic care for Canadian Indigenous populations is severely lacking currently. While many safe advanced treatments are available for debilitating diseases, including atopic dermatitis that affects ~15-20% of First Nations in Quebec, these treatments are not accessible in the Northern remote regions due to a lack of established care.

Ivan Litvinov’s proposed implementation science project will be centered on meaningful engagement of patients, health care providers (HCPs) and wider communities, continuous monitoring, analysis, and feedback based on collected data to the members of the steering committee and to the Cree Health Board/Elders overseeing the effort with the goal of achieving the Quintuple Aim (improved patient experience, better outcomes, lower costs, clinician well-being and health equity) for the region.

Ivan Litvinov’s project will leverage the existing RUISSS (Réseau Universitaire Intégré de Santé et de Services Sociaux) infrastructure to establish in-person care in 3 key Cree communities and will 1) establish a Learning Healthcare System (LHS); 2) collect quantitative and qualitative data on skin diseases, barriers and treatments; 3) recruit and support healthcare professionals to the region to foster a community of practice and promote a community of concern amongst patients through Patient and Public Involvement, knowledge mobilization and educational activities.

The impact of the project will be a co-creation of a culturally sensitive sustainable dermatologic care in the region. Results of this work will be shared with other specialties working in the region, other First Nation communities in Quebec in Canada and in other countries (e.g., Greenland).

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

Year: 2020

Geography: Canada

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. 

Determining the role of retinoic acid metabolism in acne treatment: Genetic and small molecule blockade of CYP26 in the Rhino mouse model of cystic acne

Grantee: Professor Martin Petkovich, PhD
, Cancer Research Institute Queen’s University, Kingston, Ontario

Amount: DKK 2,180,000

Grant category: Research Grants in open competition

Year: 2017

Geography: Canada

Retinoids have been used in the treatment of skin disorders for many years, particularly for hyperkeratotic diseases such as ichthyoses, psoriasis, and severe acne. Retinoid agonists are potent modulators of epidermal proliferation and differentiation, but are also associated with several side effects including hypertriglyceridemia, fatty liver, and teratogenicity.

In this project, it is believed that selective modulation of the activity of the so-called CYP26 enzymes present in skin cells and involved in inactivation of retinoic acid (RA) could provide a route to safer, equally effective treatments.

More specifically, the project uses a two-pronged approach in which:

1) The role of CYP26 is evaluated by genetic knock-out, and

2) The effect of topical administration of CYP26 inhibitors is investigated, arguing potential advantages over existing therapies by limitation of systemic increase in RA since inactivation of the enzyme is limited to the target tissue

Moreover, the project aims at showing that topical CYP26 inhibitor application is superior to topical RA agonists as the latter may induce CYP26 expression that, on repeated dosing, can limit their effectiveness; this would not be the case for CYP26 inhibitors.

Replicating peeling skin diseases in a living skin model

Grantee: Professor Peter R Hull, PhD (Med) FRCPC. Head, Division of Clinical Dermatology and Cutaneous Science, Dalhousie University, Halifax, Nova Scotia

Amount: DKK 2,180,881

Grant category: Research Grants in open competition

Year: 2017

Geography: Canada

A number of chronic skin conditions have peeling of the skin as the dominant expression; akin to skin peeling following severe sunburns. In the chronic conditions, peeling is cyclical or continuous, often affecting hands, feet, or the body. Today, there is no effective treatment for these conditions, leaving patients subjected to trial and error with a variety of non-effective and often also expensive therapies.

A number of abnormal gene variants have been found to disrupt the normal maturation of the skin. Using a gene manipulation tool known as CRISPR, the team led by Dr Hull will build understanding of the role of four known genes causing skin peeling syndromes. This will be done by replicating the diseases in cell cultures grown into full thickness skin and studying the cellular and biochemical changes caused by the induced gene modifications.

Of particular interest is cathepsin B, an enzyme that has been found to play an important role in peeling associated with the skin disorder, keratolytic winter erythema.

The team’s hypothesis is that there is an important and dynamic interplay and balance between a number of enzymes in the outer layers of the skin and that if this balance favours the activity of cathepsin B, peeling results.

If this is shown, it may be clinically very relevant as there are a number of known compounds that inhibits cathepsin B and which then could be used to treat patients with chronic peeling as a consequence of their skin disorder.