Grantee: Professor Chris Griffiths, University of Manchester, UK

Amount: DKK 8,000,000

Psoriasis is a significant, life-long and currently incurable skin disease, which, according to the first edition of the Global Psoriasis Atlas (GPA), affects at least 60 million people worldwide.

The need to understand and uncover how psoriasis impacts both the individual and society at large is in demand. The Global Psoriasis Atlas is a long-term project that seeks to become the ‘go-to’ evidence-based resource within the understanding of psoriasis and its effects on people and society all over the World.

GPA Phase II (2020-2023)

The GPA Phase II  is focused on continued research to establish robust data that address existing knowledge gaps within psoriasis on epidemiology, improving diagnosis, comorbid disease and economic impact.

Furthermore, if sufficient and robust data are available, the plan is to perform a pilot implementation study as part of GPA Phase II.

Addressing these key areas and how they differ between countries and regions will support the aim to provide better access to care for people with psoriasis worldwide.

Background

With a mission to ‘ensure that people with psoriasis, wherever they live in the world, have access to the best available care. The grant for the first version of the GPA was granted to Professor Griffiths and the University of Manchester in 2016.

The LEO Foundation has been main funder of the development of the first edition of the GPA through a 3-year grant of DKK 6,370,000 from 2017 – 2020. The GPA project has in its first three years focused on research into the global prevalence and incidence of psoriasis – resulting in the first edition of the GPA website which can be accessed free of charge here: Global Psoriasis Atlas online

 

Grantee: Sergei Koralov, Associate Professor, NYU Langone, NY, USA

Amount: DKK 2,676,248

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of blood-related cancers characterized by chronic inflammation and accumulation of malignant T cells in the skin.

The most common variant of CTCL, mycosis fungoides (MF), is often indolent in its early stages and can be managed by topical agents. However, advanced stages of MF and the systemic variant of the disease, Sezary syndrome, have a more aggressive clinical course, prove difficult to treat, are debilitating, and have no cure. CTCL is characterized by hyperactivation of the gene regulator STAT3.

We and others demonstrated the critical role of this pathway in maintaining malignant T cells. Our proposed experiments build on a recent finding that atovaquone, a well-tolerated anti-microbial drug, inhibits STAT3 signaling in mammalian cells.

We found that atovaquone triggers cell death and selectively inhibits growth of patient derived CTCL tumor cells. We now propose to use our fully penetrant animal model of this disease and primary patient cells to define precisely how atovaquone inhibits STAT3 in vivo, to establish the potential of atovaquone to treat CTCL.

The proposed studies will provide new insight into the pathogenesis of this disease and provide better understanding of the mechanism of action of this drug.

Given atovaquone’s outstanding safety and tolerability profile, the drug holds tremendous potential for the treatment of malignant and inflammatory diseases characterized by aberrant STAT3 signaling.

Grantee: Edwin En-Te Hwu, Associate Professor, Technical University of Denmark, Kgs. Lyngby, Denmark

Amount: DKK 2,824,593

The severity of atopic dermatitis (AD) is closely correlated to skin barrier.

In recent years, the nanoscale anatomy (nanotexture) on corneocytes surface was explored through atomic force microscopes (AFMs), hinting.

The number of circular nano-objects yielded a biomarker called dermal texture index (DTI). Furthermore, clinical studies revealed that the DTI is closely associated with skin barrier function.

AFMs can measure tape-stripped corneocytes nanotexture without any sample preparations. However, conventional AFMs suffer from low throughput at a high cost and limited usability in a clinical setting.

Recently, we have pioneered a unique AFM technique and we would like to integrate DTI analysis for skin barrier function assessment. This project aims to develop a tailor-made Dermal AFM that has ten times higher throughput than conventional AFMs and is easy to use in clinical environments.

The project is coordinated from DTU Health Technology and is performed in collaboration with hospitals in Denmark, Netherlands and Taiwan for AD severity assessment and skin sample acquisition.

Different regions AD nanotexture data (Europe and Asia) facilitate optimization of DTI to assess AD in a subclinical phase, as well as courses and pharmacotherapy effectiveness quantitatively. The Dermal AFM may also, in future research projects, pave the way for unveiling the science behind the corneocyte nanotexture formation.

Grantee: Andor Pivarcsi, Associate Professor, Karolinska Institutet, Stockholm, Sweden

Amount: DKK 4,164,300

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential, which accounts for 20% of all skin cancer-related deaths.

Patients with advanced tumors lack efficient treatment options, thus, there is an urgent medical need to find novel therapeutic approaches.

Long noncoding RNAs (lncRNAs) represent a crucial but as yet largely unexplored layer of gene regulation. We hypothesize that alterations in lncRNA-networks contribute to malignant progression and the that modulation of lncRNA expression can have therapeutic relevance.

Recently, we have performed a comprehensive RNAseq analysis in cSCC and identified a set of novel lncRNAs with altered expression in cSCC and whose functions are poorly characterized or completely unknown. These lncRNAs represent potential regulators of epidermal homeostasis and carcinogenesis.

In this study, we will explore the function of the identified lncRNAs in loss- and gain-of-function studies using in vitro and in vivo experimental models of cancer and differentiation, in vivo modulation of lncRNA-activity by delivery of antisense oligonucleotides (ASOs).

Additionally, we will identify the pathways regulated by cSCC-associated lncRNAs and define their mechanism of action by the biochemical characterization of binding partners.

Results of the proposed project will reveal the role of lncRNAs in epidermal carcinogenesis and pave the way towards the use of ASO-based be therapy of skin cancer.

Grantee: Peter Arkwright, Senior Lecturer, The University of Manchester, United Kingdom

Amount: DKK 4,369,423

Atopic eczema is the most common skin disease in many Western countries. Although considered an allergic disease, skin infections with S. aureus are an important cause of eczema flares. In the skin of patients suffering from eczema S. aureus predominate over “good bacteria” such as S. epidermidis (S. epi).

We work on human eczema at the University of Manchester, UK and our collaborators at TUAT University, Tokyo, Japan study a unique NC strain of mouse prone to getting eczema very similar to that seen in humans.

Together over the last 3 years, we have discovered a single factor produced by S. aureus that causes eczema in both humans and mice. We have also found that S. epi prevents the eczematous inflammation by S. aureus.

We now want to work out the exact nature of the factor produced by S. epi that prevents eczema in our system.

Using the methods, we employed in our previous collaborative study, we plan to isolate and identify the factor produced by S. epi based on its size and structure using separation columns and mass spectrometry.

We will then manipulate the genome of S. epi to confirm its identity. Finally, we will determine how the factor blocks S. aureus-driven eczema by studying how it affects S. aureus growth, as well as binding and interaction with skin cells.

Identifying this S. epi-derived factor could lead to the development of new medicines for the treatment of eczema.