Full thickness skin models from human pluripotent stem cells for identification and testing effectiveness of personalised therapies in atopic dermatitis

Grantee: Dr Dusko Ilic, MD, PhD, Reader in Stem Cell Sciences, Kings College London, Dr Reiko Tanaka, Lecturer, Department of Bioengineering, Imperial College, London, Dr Patrick Harrison, Senior Lecturer, Department of Physiology, University College Cork, Ireland, and Professor Theodora Mauro, MD, Professor of Dermatology, San Francisco Veterans Affairs Medical Center, USA

Amount: DKK 9,980,000

Grant category: Research Grants in open competition

Year: 2016

Geography: Ireland, United Kingdom, USA

This is an exciting project that, with the international group’s extensive research and know-how in mind, has the potential to create an intriguing base for novel personalised treatments for atopic dermatitis (AD). The project moreover holds an innovation potential that may make it stand out in the emerging global bio-economy.

The prevalence of AD, an inflammatory skin disease resulting in itchy, red, swollen and cracked skin, is constantly increasing. Today, it affects 15-30 percent children and 2-10 percent adults worldwide, presenting a significant economic burden to healthcare systems.

There is no cure for AD, only soothing of the symptoms. In the majority of AD patients, the disease is a consequence of a blend of genetic defects of the skin barrier defects and abnormal immune responses influenced by environmental factors.

Until now, the models used to assess the interplay are not particularly predictive. The group behind this project aims to change this by using the latest advances in stem cell science, gene editing and tissue engineering to develop and validate innovative 3D in vitro models of skin – making the models similar to skin in AD patients by emulating full thickness skin of varying barrier integrity; faulty, partially repaired or intact, and immune response composition.

As part of the project, the group will also develop mathematical computer models to accurately address the predictive, prognostic and therapeutic outcome of personalised AD therapy – in order to address co-dependence of the quantitative and qualitative changes in skin barrier and activation of immune cells.

The 3D models will also be made available to test various novel therapeutic approaches for AD treatment in a patient specific manner.

Big Bang – support for Denmark’s largest science conference

Grantee: Astra, the national Centre for Learning in Science, Technology and Health in Denmark, Copenhagen

Amount: DKK 2,000,000

Grant category: Education and Awareness Grants

Year: 2016

Geography: Denmark

Denmark’s largest science conference, the Big Bang Conference, has received two million Danish kroner over the next three years from the LEO Foundation.

Big Bang is the largest Danish science conference and exhibition targeted all who teaches, facilitates or researches in the science and science fields – in primary and secondary schools and higher education.

The conference, held once a year, gathers more than 1,000 people for two involving and inspiring days with relevant keynote speakers, a humming exhibition atmosphere, involving workshops and novel ideas for the continued renewal of science education.

The conference is held next on 23 and 24th March 2017 in Odense Congress Center, Denmark.

www.bigbangkonferencen.dk

Melanocyte stress response pathways and their role in the onset of vitiligo

Grantee: Prashiela Manga, PhD
, Associate Professor Dermatology and Cell Biology, New York University School of Medicine

Amount: DKK 5,037,192

Grant category: Research Grants in open competition

Year: 2016

Geography: USA

Vitiligo, an acquired skin disease in which pigment cells, melanocytes, are destroyed, affects 1-2% of people worldwide. The disease deprives the skin of photoprotection leaving it more susceptible to solar damage and compromised cutaneous immunity – and the disease impacts physical and mental health.

Vitiligo is thought to occur in genetically susceptible individuals after being exposed to environmental triggers. Some individuals develop contact vitiligo after direct exposure to certain chemicals. As disease progression in vitiligo is independent from initiating factors, this subset of individuals makes it possible to study vitiligo at large.

The hypothesis in this project is that melanocytes from healthy individuals can withstand exposure to triggers by initiating a stress response regimen that allows the cell to return to homeostasis. These pathways may be disrupted in individuals who develop vitiligo, leaving melanocytes stressed following challenge, causing them to be targeted for removal by the immune system.

In order to investigate this hypothesis, the project will investigate survival pathways in melanocytes cultured from biopsies taken from pigmented skin from individuals who have developed vitiligo.

Development and validation of scoring systems for outcome measures of vitiligo: an international cooperative initiative

Grantee: Professor, Dr Nanja van Geel, Department of Dermatology, Ghent University Hospital, Ghent

Amount: DKK 735,000

Grant category: Research Grants in open competition

Year: 2016

Geography: Belgium

Clinical trials for vitiligo – a skin disease that causes loss of skin color in blotches – lack uniformity in reported outcomes and the measurements hereof. This lack of uniformity hampers development of general treatment guidelines, as it limits appropriate interpretation and comparison of results. In particular, since vitiligo is without biomarkers, clinical measurement tools are crucial to assess disease extent.

A recently introduced scoring instrument, Vitiligo Extent Score (VES), will play a central role in this international project. The project team comprises researchers from Belgium, Netherlands, France, Italy, and the UK, and their aim is to create a worldwide consensus on measuring disease severity.

The VES was designed to be intuitive, fast and accurate, and the team has successfully performed an initial validation for estimating global disease extent. The aim of this project is to further develop and validate reliable and feasible instruments to assess vitiligo status in order to improve evidence-based therapeutic decisions and develop novel treatments.

Hereafter, the tool will be used for the development of other scoring methods including a patient-reported outcome measure, a physician global assessment, a vitiligo disease activity score, and a digital image analysis system for target lesions.

International Eczema Council

Grantee: Amy Paller, MS, MD, IEC President, Professor of Dermatology and Professor of Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, and Emma Guttman-Yassky, MD, PhD, IEC President-Elect, Associate Professor of Dermatology & Immunology, Department of Dermatology, Icahn School of Medicine, Mount Sinai, New York

Amount: DKK 340,000

Grant category: Research Grants in open competition

Year: 2016

Geography: USA

The IEC is convening a meeting at the ESDR in September 2015 to write a position paper on Atopic Dermatitis as a systemic disease.

In March 2016, the IEC will hold a session at the Annual AAD in Washington, D.C. focusing on AD phenotyping – starting to use biomarkers to assess subgroups of AD, which may be relevant to the understanding of disease and treatment decision-making.

Development and validation of a physiologically-based pharmacokinetic model for dermal absorption

Grantee: Dr. Richard H. Guy, Professor of Pharmaceutical Sciences & Dr. M. Begona Delgado-Charro, Associate Professor of Pharmaceutics, University of Bath

Amount: DKK 3,564,000

Grant category: Research Grants in open competition

Year: 2016

Geography: United Kingdom

The project aims to develop a physiologically based pharmacokinetic model to predict the dermal absorption and disposition of drugs included in complex topical products.

A distinctive feature of the research is the integration of formulation-dependent information derived experimentally, and a deliberate strategy to facilitate the practical implementation of the model for a wide range of drugs.

The long-term goal is to develop a model, which will predict drug absorption and disposition from dermal products thereby facilitating their optimisation and, ultimately, the development of high-performance medicines.

The LEO Foundation Award 2015 – Silver Award

Grantee: Dr. Kilian Eyerich

Amount: DKK 500,000

Grant category: LEO Foundation Awards

Year: 2015

Geography: Germany

Presented to Dr. Kilian Eyerich, Assistant Professor, Experimental Dermato-Immunology, School of Medicine, Technische Universität München, Germany.

Early in his career, Dr. Eyerich studied the cross-talk between keratinocytes and T cells usingco-cultures.His work on the role of Th17 and Th22 cells in the skin has significantly enhanced molecular understanding of atopic dermatitis and psoriasis. Dr. Eyerich has identified a unique group of patients with co-existing inflammatory skin diseases and demonstrated the mutual antagonism of T cells causing atopic dermatitis and psoriasis.

The LEO Foundation Award 2015 – Gold Award

Grantee: Dr. Nicola Segata

Amount: DKK 1,000,000

Grant category: LEO Foundation Awards

Year: 2015

Geography: Italy

Presented to Dr. Nicola Segata, Assistant Professor and Principal Investigator, Laboratory of Computational Metagenomics, Centre for Integrative Biology, University of Trento, Italy.

Dr. Segata has pioneered novel advanced techniques for the characterisation of the microorganisms colonising the human body (the microbiome). His discoveries have proven to be crucial in studying microbial communities and unravelling the structure of the human skin microbiome. The characterisation of the microbiome is a fast-growing research field because it plays an important role in many pathological conditions, including skin diseases such as atopic dermatitis, acne, psoriasis and rosacea.

The natural history of skin cancer formation: from normal skin to cancer

Grantee: Associate Professor Kiarash Khosrotehrani, University of Queensland

Amount: AUD 268,239

Grant category: Research Grants in open competition

Year: 2015

Geography: Australia

Associate Professor Kiarash Khosrotehrani from The University of Queensland leads a team that has hypothesized that upon UV irradiation and acquisitions of mutations, only epidermal cells that can rapidly proliferate are likely to give rise to pre-cancerous and cancerous lesions.

This hypothesis will be tested using multicolour lineage tracing to follow simultaneously multiple epidermal clones that will further be microdissected to establish their mutational profile.  This study has the potential to fundamentally change our understanding of field cancerisation, cell of origin of squamous cell cancer establishing potentially new therapeutic targets.

Preventing Basal Cell Carcinoma formation by targeting the tumor environment

Grantee: Associate Professor Kiarash Khosrotehrani, University of Queensland

Amount: AUD 415,386

Grant category: Research Grants in open competition

Year: 2015

Geography: Australia

In this study, Associate Professor Kiarash Khosrotehrani of The University of Queensland in Australia proposes to better characterise the molecular nature of the factors provided by fibroblasts to support basal cell carcinoma (BCC) growth in vivo in order to find new targets for therapies that would prevent BCC development. He and his team will also show proof of principle demonstrating that targeting this process can actually prevent BCC development.

These findings have the potential to translate in effective prevention strategies, allowing field therapy of normal looking skin to avoid the development of new BCCs. Such finding will have strong health benefits in terms of morbidity associated with multiple surgeries, years of healthy life enjoyed by individuals and finally in terms of economic cost.