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Donations and beneficiaries 2017

The contents of this section will be part of the management review from the LEO Foundation’s annual report 2017.

Click on the title of the individual project to unfold.

GLP-1R signaling in T cells in relation to psoriasis

Beneficiary: Carsten Geisler, Professor and Head of Department, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen

 

Donation: DKK 2,000,000

 

Recent studies of patients with psoriasis and type 2-diabetes have shown intriguing results: administration of glucagon-like peptide 1 (GLP-1) analogues was found to improve the severity of psoriasis. In another study, while not finding a significant beneficial effect of a GLP-1 analogue on disease score as compared to placebo, patients did report a significant decrease in their disease score as compared to baseline.

 

This has led a Denmark-based group to team up for further investigation of the effect of GLP-1 analogues on psoriasis, based on, among others, an assumption of a direct effect of GLP-1 analogues on the immune system – with the intention of clarifying if there may be a route to new treatment options for psoriatic patients.

 

More specifically, the team will investigate if the potential immunoregulatory effect of GLP-1R signalling on T cells in psoriatic plaques could be responsible for the patient-experienced alleviation of psoriasis. The team furthermore hypothesizes that vitamin D may play an important role in GLP-1R signaling and is important for alleviation of psoriasis as Vitamin D upregulates GLP-1R on T cells and low serum levels of vitamin D have been reported in psoriatic patients.

 

The majority of the experiments will be performed by Anna Kathrine Obelitz Rode under supervision of Martin Kongsbak-Wismann and Carsten Geisler, Department of Immunology and Microbiology, University of Copenhagen. Lone Skov, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen will be co-supervisor on the project. The project will be performed in close collaboration with Charlotte Menné Bonefeld, Department of Immunology and Microbiology, University of Copenhagen.

 

The clinical studies in humans will be performed at the Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen in collaboration with Lone Skov.

Towards a personalized medicine approach for atopic dermatitis

Beneficiary: Dr Emma Guttmann, Icahn School of Medicine at Mount Sinai, New York, NY, USA

 

Donation: DKK 4,700,000

 

Atopic dermatitis (AD) is the most common inflammatory skin disease, with a prevalence in adults of 3% to 10% and a large unmet need for effective therapeutics.

 

Current clinical trials for AD patients assume a common disease mechanism. However, based on preliminary data, different therapeutics may be required to effectively treat different subsets of AD patients.

 

Biomarker-based studies show distinct clinical, and particularly molecular and cellular differences between different AD subpopulations such as African American, Chinese, and Indian AD patient populations.

 

However the characterization of the different and distinct clinical AD phenotypes is still at its very beginning. Indeed, there is high need of appropriate mechanistic studies to create a complete “molecular map” of AD across its different variants and hence to get a step closer for a personalized treatment approach.

 

Dr. Emma Guttman and her team at Icahn School of Medicine at the Mount Sinai Medical Centre, NY, USA, will seek a first time investigation to provide a systems biology approach for AD aiming to produce a molecular map of AD across its different subtypes.

 

The project integrates cellular and molecular biomarkers of lesional, but also non-lesional, skin and systemic inflammation to classify adult AD patients based on ethnic phenotypes, disease severity and age differences.

 

The proposal will set the stage for personalized therapy approach for AD based on skin and blood biomarkers and pathogenic variation of AD phenotypes related to severity, race/ethnicity and age.

Epidermal and Dermal Stem Cells in Psoriasis

Beneficiaries: Markus Frank, MD, Associate Professor, Harvard Medical School, Boston Children’s Hospital, Boston, Massachusetts, USA; Christine G. Lian, MD, Assistant Professor, and George F. Murphy, MD, Professor, both Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, USA

 

Donation: DKK 3,000,000

 

Despite decades of research, the root cause of psoriasis remains unknown and targeted approaches to cure psoriasis have to date been elusive.

 

Psoriasis is a physically and psychologically devastating skin disorder affecting more than 7.5 million Americans, with global prevalence ranging up to 4.6%. The disease causes profound physical, emotional, and social burdens translating into massive healthcare costs.

 

Theories of the biological mechanisms behind the disease range from genetic and epigenetic deviations to acquired defects involving a plethora of cellular and mechanistic culprits, including epidermal cell kinetics, endothelial-leukocyte interactions and perturbations in dermal nerve fibres, mast cells, lymphocytes and dendritic cells.

 

However, even if it is clear that a multiplicity of cellular pathways is involved, the primary events that initiate and drive disease remain unknown.

 

The team behind this study proposes a novel hypothesis that psoriasis is driven by immune-mediated dysregulation of stem cells within the epidermal and dermal compartments.

 

In the course of the study, the team will, for the first time, test the skin stem cell hypothesis of psoriasis causation with a highly-focused goal of defining the primary event(s) in lesion formation, thus providing a foundation for future pre-clinical targeted therapeutic approaches designed to actually cure psoriasis.

The pro-autophagic tumor suppressor AMBRA1 as a novel therapeutic target for melanoma

Beneficiary: Prof. Francesco Cecconi, Head of the Cell Stress and Survival Unit (CSS), Danish Cancer Society Research Center (DCRC), Copenhagen, Denmark

 

Donation: DKK 3,820,000

 

The LEO Foundation has supported this project in appreciation of the fact that malignant melanoma has the highest death toll among skin cancer.

 

If and when melanoma is not diagnosed and treated early, the cancer may develop and spread to other parts of the body, where it becomes harder to treat and potentially fatal. Therefore, work to find new therapeutic targets for this particular aggressive cancer type is of extreme importance.

 

Prof. Francesco Cecconi and his team have extensive and comprehensive expertise on the molecular ‘switch’ AMBRA1, believed to play a significant role in the body’s own defense against diseases such as cancer.

 

Prof. Cecconi, as an example, was the first to identify the AMBRA1 gene and has been unraveling its multiple functions over the last 10 years. In particular, he has already demonstrated AMBRA1 playing a role as tumor suppressor in vivo, and preliminary data indicates the gene’s supposed role as a therapeutic target in cancer. Very intriguingly, most AMBRA1 mutations were found in melanoma patients.

 

The LEO Foundation finds this project to be innovative and commends its multidisciplinary approach, putting together different fields of research ranging from cell biology, mouse genetics, biophysics, computational biology and CRISPR/Cas9 technology.

 

Prof. Cecconi is member of the European Consortium Mel-Plex (Horizon 2020 Marie Curie Action), which includes several international researchers with the common aim of tackling melanoma – and these existing collaborations with melanoma experts will be of great importance in order to accomplish the project.

Donations and beneficiaries 2016

The contents of this section is part of the management review from the LEO Foundation’s annual report 2016.

 

Click on the title of the individual project to unfold.

Influence of microbes on development of skin diseases

Beneficiaries: Anders Johannes Hansen, PhD, Associate Professor, University of Copenhagen, Denmark, Robert Gniadecki, MD, Professor, Dermatology Department, Bispebjerg Hospital, Copenhagen, Kim Holmstrøm, R&D Manager, Department of Biomedical Technology, Bioneer A/S, Denmark & Nicola Segata, PhD, Assistant Professor and Principal Investigator, Computational Metagenomics, CIBIO, University of Trento, Italy

 

Donation: DKK 5,035,000

 

By combining new data from the human skin microbiome with existing knowledge of pathophysiology and clinical phenotypes of Atopic Dermatitis, AD, Actinic Keratosis, AK and non-melanoma skin cancer, the team will seek to establish a novel understanding of these diseases.

 

Recent microbiome analyses have revealed that mammalian body surfaces are colonized by vast numbers of bacterial communities, which motivates the exploration of the role of the microbiota in normal and diseased skin. There are indications that the skin microbiome plays a key role in both inflammatory skin disease and non-melanoma skin cancer.

 

The vision for the team’s research endeavours is to explore the microbiome for the identification of new targets for treatment, and for the development of improved treatment modalities for patients with AD, AK and non-melanoma skin cancer.

 

The team’s explorations will potentially also lead to the development of better and more specific and sensitive diagnostic and prognostic methods for monitoring skin disease.

 

The Danish-Italian team will work from a unique microbiome discovery platform established at the University of Copenhagen (UCPH) within the GenomeDenmark Cancer & Pathogen project. The platform utilizes procedures enriching various types of microbes combined with state of the art DNA and RNA sequencing and bioinformatics data analysis.

Skin barrier dysfunction and thymus size during the first year of life as predictors for atopic dermatitis

Beneficiaries: Jacob P. Thyssen MD PhD DmSci, Trine Danvad Nilausen MD, Lone Skov MD PhD DmSci, Dep. Dermatology and Allergology, Herlev-Gentofte Hospital, Hellerup, Denmark, Caroline Ewertsen MD PhD, Department of Radiology, Rigshospitalet, Copenhagen, Denmark, Charlotte Bonefeld PhD, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Pal Szecsi MD DmSci, Department of Clinical Biochemistry, Herlev-Gentofte Hospital, Hellerup , Denmark, Sanja Kezic PhD, Coronel Institute, AMC, University of Amsterdam, The Netherlands, and Christoph Riethmüller PhD, nAnostic Institute, Centre for Nanotechnology, University of Münster, Germany

 

 

Donation: DKK 2,558,500

 

 

The study is foreseen to increase the understanding of the skin barrier and immune system in atopic dermatitis.

 

Through international collaboration with scientists who perform state of the art and pioneering analyses on skin samples as well as national collaboration with immunologists and radiologists, the team will seek to evaluate non-invasive and easily collectable biomarkers that can predict the risk for atopic dermatitis.

 

The study has the potential to provide insight in atopic dermatitis pathogenesis and the value of promising pre-atopic dermatitis biomarkers that indicate both inflammation and skin barrier barriers dysfunction. This could be used to develop an algorithm that can better predict the onset of atopic dermatitis.

 

The team’s work may thus substantially increase the understanding of skin biology in neonates, both normal and diseased. The study will also provide a basis for not only future large-scale observational studies, but also randomised controlled studies evaluating the efficacy of preventive skin barrier restoration or anti-inflammatory treatment in selected groups, potentially reducing the incidence and complications of the most common skin disease in childhood.

The Human Skin Immune Atlas: Three-dimensional reconstruction of serial histology and computational image analysis of dermal immune populations in normal and diseased skin

Beneficiaries: Philip L. Tong, PhD, Department of Dermatology, Royal Prince Albert Hospital, University of Sydney, Australia, Dr Ben Roediger and Professor Wolgang Weninger, Centenary Institute, Newtown, Australia, and Dr Weimiao Yu, Institute of Molecular and Cell Biology, A*STAR, Singapore

 

Donation: DKK 708.500

 

This research project, led by Dr Philip Tong from the University of Sydney, has the potential to represent a technological advancement in the field of human skin immunological research. By use of 3D histological reconstruction and computational image analysis, the aim is to develop the world’s first Human Skin Immune Atlas of dermal immune populations in normal and diseased skin.

 

The members of the team assembled for this project are already established experts in the fields of skin immunology, microscopy, inflammation and computational analysis, and the project will have an international platform with sites across Asia and Oceania.

 

The skin is a complex organ, wherein topographical and micro-compartmental specialisation of the immune system has been demonstrated. The general spatial understanding of the skin immune system has been advanced through the use of transgenic laboratory animals with live imaging tools. These, however, have yet to be validated in humans. The work realised in this project may provide fundamental insights into the human skin immune system.

 

Moreover, the data generated may have wide reaching implications for the development of better in vitro skin substitutes, validation of in vivo microscopic skin imaging tools for human use and improved quantification of skin inflammation in clinical trial settings.

Skin and blood biomarkers of atopic dermatitis in different paediatric age groups

Beneficiary: Dr Emma Guttmann, Icahn School of Medicine at Mount Sinai, New York, NY, USA

 

Donation: DKK 11,500,000

 

Atopic dermatitis (AD), or atopic eczema, is the world’s most common inflammatory skin disorder. Its prevalence has increased during the past few decades and can now be found to be more than 20% in children and 10% in adults.

 

For children, there is an unmet need for improved therapy for moderate to severe AD and it is likely that therapeutics with proven safety and efficacy in adults will move towards to trials in children. There are, however, when gauging the pathogenesis and characteristic biomarkers related to AD, significant differences between children and adults.

 

Dr. Guttmann’s study purports to shed light on these differences to enlarge the understanding of biomarkers and to clarify when children transition to the adult biomarker pattern that predicts responses. Correlating the validity of biomarkers in adults with AD vs. different age groups of children and adolescents with AD (including 5-12 and 12-17 years olds) is a critical step before engaging in large clinical trials.

 

Given the challenge in obtaining biopsies from children during clinical trials, defining a set of biomarkers in blood will prove extremely valuable in these large patient populations. More specifically, the study will address the following questions:

 

  • What are the cutaneous biomarkers in AD in children and adolescents of different age groups and how do these compare with disease activity, epidermal barrier function, and known biomarkers in both infancy/early childhood and adult AD skin?
  • Are there useful biomarkers in the blood of children and adolescents with AD that compare well with skin immune and barrier biomarkers, and could these enable a less invasive means to follow biomarker changes and direct skin therapy than skin biopsies?
  • At what age do children acquire an “adult” AD phenotype?

A longitudinal investigation of skin barrier development from birth and the validation of early predictors of AD risk: the skin testing for atopic dermatitis risk (STAR) trial

Beneficiaries: Dr Simon G. Danby, Independent Research Fellow, University of Sheffield Medical School, UK, Professor Michael J. Cork and Mr J. Chittock, University of Sheffield, UK, and Dame, Professor Tina Lavender and Dr Alison Cooke, The University of Manchester, UK

 

Donation: DKK 2,115,500

 

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin conditions and prevalence of the disease seems to grow. Early onset of AD is often followed by development of other allergic conditions such as food allergies, asthma and allergic rhinitis – all together the most chronic diseases of childhood and a major financial burden to health services.

 

Evidence suggests that a skin barrier defect is the primary event in development of AD.

 

With this research project, a longitudinal neonate/infant cohort study, the team led by Dr Michael G. Danby seeks to investigate the development of the skin barrier from birth, before the development of AD, to 12 months of age, when the majority of AD cases have developed. The team has extensive experience in the characterisation of the skin barrier in AD patients and in conducting clinical trials in neonates.

 

In the study, the team will compare three technologies for the quantification of established biomarkers attributed to skin barrier function and AD severity, for their accuracy and feasibility at predicting onset of AD by 12 months of age.

 

In addition, the team’s multi-analytical approach may provide new insights into skin barrier development in neonates and the identification of tools that could help determine who do and do not go onto develop AD. The study thus has the potential to help drive forth a new generation of patient solutions specifically designed for neonates at risk of developing AD.

Chemiexcitation in Human Disease

Beneficiaries: Douglas E. Brash, PhD, Professor, Departments Therapeutic Radiology and Dermatology, Yale School of Medicine, New Haven, CT, USA, and Etelvino Bechara, PhD, Professor, Institute of Chemistry, University Sao Paulo & Federal University, Sao Paulo, Brazil

 

Donation: DKK 281,000

 

The LEO Foundation has granted support to a conference on chemiexcitation in human disease to be held at the Cold Spring Harbor Laboratory, Long Island, NY. The initiative will bring together a select group of internationally renowned scientists with the goal of combining expertise from several fields to explore the ramifications of a previously unrecognized mode of disease – chemical excitation of electrons (“chemiexcitation”).

 

Chemiexcitation is a high-energy biophysical process that underlies bioluminescence, but it had not been observed in mammals until a finding that chemiexcitation sent melanocytes down the path to melanoma when two key enzymes were activated by ultraviolet light.

 

The insight driving the conference is that the same chemistry will occur wherever nitric oxide, superoxide, and melanin are present at the same time, so chemiexcitation may also be a hidden step in diseases where sunlight is not involved.

 

The three chemical reactants co-occur during inflammation and ischemia-reperfusion injury, so chemiexcitation may underlie skin cancers arising in burn scars and it may operate during wound healing, hypertrophic scarring, skin flap reconstructive surgery, and skin aging. The same reactants are also present in neurodegenerations such as Parkinson’s Disease and Alzheimer’s, in deafness induced by noise or drugs, and in macular degeneration.

 

A first outcome of the 3.5 day conference will be a white paper outlining plausible chemiexcitation pathways for the diseases or pathologic reactions as well as identifying promising avenues of scientific investigation and feasible routes to blocking chemiexcitation.

 

A second outcome will be a website to provide a technical foundation for new colleagues – including young scientists. Modified versions of slides from the conference will be posted, including a recollection of what is already understood in each area, and presented as a list of principles and expositions in the style of Molecular Biology of the Gene. The website will also present lists of resources and the chemistry, biology, and pathology questions that are still in need of an answer.

Serum transcriptomics in melanoma patients

Beneficiary: Igor Vujic, MD, Assistant Professor, Sigmund Freud University & Department of Dermatology, Rudolfstiftung Hospital, Vienna, Austria

 

Donation: DKK 265,000

 

The Austrian-American team behind the study, led by Dr. Igor Vujic, aims at identifying more specific and sensitive biomarkers in order to better detect and monitor progression of malignant melanoma – a common and deadly skin cancer that is difficult to treat, and that accounts for numerous deaths each year.

 

In the clinic, physicians face two main problems around malignant melanoma: detection of early disease, and monitoring of disease progression, recurrence and its response to therapies. The existing melanoma biomarkers are not very specific and only rarely help.

 

Melanoma cells, however, produce a specific set of RNA molecules of which some are excreted and found in the blood stream – ready for identification and use as biomarkers. Recent technical advances make it possible to extract and analyse serum RNA and identify the cell of origin.

 

The team will mainly concentrate on non-coding RNAs, a new class of molecules known to be very specific for certain diseases such as cancer. Preliminary studies have identified and confirmed 237 interesting candidates through RNA-Seq TCGA (The Cancer Genome Atlas) data.

 

In the course of the study, the team will perform RNA-Seq studies on serum samples from melanoma patients and healthy individuals to find differences in RNA quality and quantity to be used as melanoma serum-markers. The team will moreover test changes of the amount of these specific RNA molecules in melanoma patients over time to discover if they can be used as disease progression biomarkers.

Developing deep understanding of atopic dermatitis

Beneficiaries: Joel Dudley, PhD, Director of Biomedical informatics, Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, USA, and Jeanne Duus Johansen, MD, DMSc, Director National Allergy Research Centre, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Denmark

 

Donation: DKK 11,100,000

 

Atopic dermatitis (AD) and hand dermatitis are heterogeneous disease entities and there has yet to be developed a good understanding of their many different clinical aspects. Thus it remains extremely challenging to provide patients with better treatment outcomes and prognosis.

 

A newly formed team of scientists at Gentofte Hospital in Copenhagen and Mount Sinai in New York has set out to change this.

 

“Next generation sequencing and advanced bioinformatics technologies give us powerful new opportunities to explore and understand the molecular pathophysiology of atopic dermatitis and hand dermatitis,” says Dr. Joel Dudley, Director of Biomedical informatics at Icahn School of Medicine, Mount Sinai in New York.

 

“It is a study that has not previously been performed, and we expect to make a breakthrough in the understanding, classification and treatment of these skin diseases. We hope to improve our knowledge and understanding of the molecular basis of atopic dermatitis and hand dermatitis and their relation to clinical features. Consequently, we also hope to pave the way for improved opportunities for managing and preventing disease,” says Dr. Jeanne Duus Johansen from the Department of Dermato-Allergology at Gentofte Hospital.

 

She and Joel Dudley will lead a trans-Atlantic team of researchers working with high-throughput, genome-wide profiling of multiple of the ‘–omics’ modalities, including genome, transcriptome, epigenome and microbiome.

 

The goal is to develop a deeper understanding of how the molecular manifestation of the heterogeneous diseases correlates with clinical variables such as onset of disease and treatment outcomes. The technologies employed by the team can provide comprehensive molecular profiles that can enhance the understanding of the system-wide mechanics and properties of complex biological systems.

 

Dudley’s team will integrate the ‘-omics’ data sets to clarify the complex biological mechanisms underlying disease. They will do so by connecting molecular profiles with clinical data to identify molecular surrogates of drivers of important clinical features of disease.

 

The study will build on previous efforts to assemble and characterise a Danish cohort of individuals affected by AD in adulthood and/or hand dermatitis. The proposed study will add important new dimensions of molecular information that will enable new insights into molecular mechanisms and features of disease. Furthermore, the team sees that an incorporation of molecular measures, namely microbiome and epigenome, may offer insight into environmental correlates or determinants of disease.

 

Finally, the team foresees that the data and results generated may serve as an important new asset to the AD and dermatology research communities.

 

“We believe that the data and results generated by our study will enable new research directions and insights into AD and dermatological disease. Furthermore, we believe that such future insights would be enabled by the unique availability of the proposed comprehensive multi-omics data set integrated with comprehensive clinical data and assessment of a large patient cohort,” explains Dr. Jeanne Duus Johansen.

Cardiovascular risk in psoriasis – meeting a profound clinical need

Beneficiaries: Joel Dudley, PhD, Director of Biomedical informatics, Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, USA, and Peter Riis Hansen, MD, DMSc, PhD, Consultant (invasive cardiology), Associate Professor, Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark

 

Donation: DKK 13,100,000

 

Cardiovascular diseases (CVD), such as myocardial infarction and stroke, are leading causes of death globally. Independent of traditional risk factors, however, psoriasis patients run an increased risk of CVD, adding considerably to morbidity and mortality for this large patient group.

 

“Inflammation has been proposed as a part of the explanation for the association between psoriasis and CVD. However, when we look at the underlying pathophysiology and molecular drivers of this connection, they are unclear. It is also unresolved whether treatment responses for psoriasis alter the course of CVD. To us, this suggests that the connection with inflammation might be more complex than currently appreciated,” says Joel Dudley, Director of Biomedical informatics at Icahn School of Medicine, Mount Sinai in New York.

 

Together with Peter Riis Hansen, Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark, Dudley will lead a team focused on developing a much needed understanding between the molecular mechanisms of psoriasis and the increase in CVD comorbidity. Understanding these complex interactions between skin and cardiovascular health will lead to insights for future preventive treatments and improved prognosis.

 

The team will employ an array of modern high throughput technologies to bring together information about genetics, immunology, local gene expression, microbiomes, and more standard clinical measures to develop an unprecedented map of factors impacting cardiovascular health in psoriatic patients.

 

“We will apply sophisticated bioinformatics and network biology techniques to integrate the data and develop a disease network model that will enable both discovery and testing of novel hypotheses concerning biomarkers and pathogenic mechanisms. We believe that this disease network model will serve as a powerful and unprecedented resource for the dermatology, cardiology, and immunology research communities,” says Peter Riis Hansen.

 

More specifically, the model may facilitate the re-interpretation of data from previous studies and clinical trials, be queried by scientific and clinical investigators to evaluate novel clinical and molecular hypotheses, and inform new understanding of fundamental molecular mechanisms underlying the interplay between skin biology, immune function, and the immune-metabolic-cardiovascular axis.

 

The resulting disease network model may also uncover molecular mechanisms contributing to increased CVD risk in other immune disorders, such as rheumatoid arthritis, atopic dermatitis, and inflammatory bowel disease.

 

“We believe that the data generation activities alone would provide tremendous value to the research community, and that developments in data analysis and bioinformatics has the potential to increase exponentially our understanding of molecular mechanisms underlying CVD risk in inflammatory skin disease,” says Peter Riis Hansen.

Cytosolic genome DNA fragments as a trigger of keratinocyte proliferation in psoriasis

Beneficiary: Dr Koichi Suzuki, PhD, Professor, Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Japan

 

Donation: DKK 460,000

 

Release of double-stranded (ds)DNA from keratinocytes has been linked to the initiation of psoriasis via induction of an immune response. Furthermore, vitamin D has been reported to interfere with this mechanism. Vitamin D analogues are widely used for treatment of psoriasis and have a well-known effect on keratinocyte proliferation and differentiation.

 

Dr Koichi Suzuki and his Japanese-Chinese team hypothesise that the release of dsDNA may more directly induce the characteristic hyper-proliferation and abnormal differentiation of keratinocytes seen in psoriasis by a TNFα-mediated inflammatory process in keratinocytes.

 

The team will investigate this hypothesis and the impact of vitamin D by the use of keratinocyte cultures and psoriasis skin samples from patients treated with a vitamin D analogue.

 

The project may further enhance our understanding of the complex molecular events underlying psoriasis and how vitamin D treatment may intervene in the pathogenic process, potentially revealing new aspects of the mode of action of vitamin D.

Defining the epigenetics of rosacea

Beneficiary: Luis Garza, Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, MD, USA

 

Donation: DKK 330,000

 

Rosacea affects many people around the globe and treatments could be better and more efficient. Defining new possible treatments will not only satisfy this clinical need, but also offer the opportunity to learn about the pathogenesis of rosacea and subsequent basic knowledge about skin biology.

 

The discovery of the role of the innate immunity in rosacea has generated many interesting new avenues for investigation.

 

The team led by Luis Garza points to the fundamental role of keratinocytes in disease pathogenesis as a critical insight given that keratinocytes, more than fibroblasts for example, contribute to innate immunity pathways.

 

This, they say, begs an interesting question: if keratinocyte turnover is so rapid such that entirely new cells are present every several months, how is the propensity for rosacea so robustly inherited from ‘mother’ to ‘daughter’ keratinocyte?

 

The team hypothesises that epigenetic lesions are more likely to explain the mostly adulthood acquisition of rosacea and the stability of disease in adulthood rather than DNA mutations. With this project, the team has the potential to generate data that can be used in academics and industry to measure improvements and severity of rosacea through its epigenetic profile.

Skin barrier function is first line of defence – Epidermal T cells dynamic, interplay and function

Beneficiary: Charlotte Menné Bonefeld, Associated Professor, Department of Immunology and Microbiology, University of Copenhagen, Denmark

 

Donation: 2.385.900 DKK

 

The skin provides the first barrier of defence between the body and the environment. It is one of the largest organs of the human body and is constantly being exposed to pathogens and environmental triggers.

 

The outermost layer of the skin is the epidermis and it consists of a variety of both immune and non-immune cell types. Among the immune cells within epidermis are the T cells. One of the important characteristics of T cells is that they can develop into memory T cells following their activation.

 

Experimental work is often done with mice, but experience shows that there is difference between T cells in humans and mice epidermis – a difference that until recently has been thought related to species diversity.

 

Recent findings, however, have shown that environmental triggering factors, such as microorganisms or chemical irritants, lead to a dynamic shaping of the type of T cells present in the epidermis. Based on these discoveries, the team led by Charlotte Menné Bonefeld has hypothesised that the difference between T cells in human and mice epidermis are not mediated by species differences, but rather by difference in skin exposure to microorganisms and chemicals that occurs early and throughout the whole life.

 

Therefore, the team will investigate i) the similarities and differences of T cells in human and mice epidermis, ii) the effect of allergen and infection agents on the phenotype and activity of epidermal T cells and iii) the interplay between epidermal immune cells forming the immunological barrier properties of the skin.

 

Answering these questions will be crucial for developing better treatments for inflammatory skin diseases as it is very likely that these mechanisms play a central role in the pathogenesis of several inflammatory skin diseases like allergic contact dermatitis, atopic dermatitis and psoriasis.

ICR Agonists as novel therapeutics for psoriasis treatment

Beneficiary: Vasileios Bekiaris, Ph.D., Associate Professor, Section for Immunology and Vaccinology, National Veterinary Institute, Danish Technical University, Denmark

 

Donation: DKK 1,047,816

 

Psoriasis and most autoimmune diseases are characterised by a deregulated hyper activation of T cells leading to chronic tissue destruction and in many cases significant morbidity. Immune checkpoint receptors (ICRs) negatively regulate the immune system by dampening lymphocyte functionality.

 

Bekiaris and his team have, as have others, shown that manipulation of these ICRs can alter the outcome of the immune response; a strategy currently successful in cancer immunotherapy.

 

In this project the team will use the mouse psoriasis-model (IMQ) to test the hypothesis that in vivo activation of specific ICRs will block the induction and progression of psoriasis. In addition, the team aims to characterise the importance of ICR signalling during the course of psoriasis, both at the cellular and molecular levels.

 

The study will delineate the molecular mechanisms underlying ICR signalling during skin inflammation and potentially create a new pathway for possible future treatment of psoriasis though opening of new targets.

The LEO Foundation rewards young scientists in Japan

Beneficiaries: Dr. Ayumi Yoshizaki, lecturer and independent researcher, Department of Dermatology, Graduate School of Medicine, The University of Tokyo & Dr. Yu Sawada, research fellow, Department of Dermatology, Kyoto University and assistant professor, University of Environmental and Medical Health, Kitakyushu

 

Donations: DKK 500,000 & DKK 250,000

 

The LEO Foundation has offered “LEO Foundation Awards 2016 in association with JSID” to two young, promising Japanese scientists for their pioneering dermatological research. The awards have been bestowed in collaboration with the Japanese Society for Investigative Dermatology (JSID).

 

The LEO Foundation Gold Award of DKK 500,000 went to Dr. Ayumi Yoshizaki, and the DKK 250,000 Silver Award went to Dr. Yu Sawada. The award ceremony took place in Sendai, Japan, at the 41st annual conference of JSID on 11 December 2016.

 

About the awardees

Gold award winner: Dr. Ayumi Yoshizaki is a lecturer and an independent researcher in the field of dermatological autoimmune diseases based at Department of Dermatology, Graduate School of Medicine, The University of Tokyo. Dr. Yoshizaki has his own research group, an impressive list of publications and is well acknowledged by the Japanese dermatological and scientific communities. His future research is focused on autoimmune diseases related to the skin, particularly systemic sclerosis (SSc). His lab uses highly innovative techniques to explore the role of auto-reactive B cells in SSc at the single cell level. He is a rising star that very well could establish himself as a leader in his field globally.

 

Silver award winner: Dr. Yu Sawada currently holds the position as a research fellow at the Department of Dermatology in Kyoto University and assistant professor at the University of Environmental and Medical Health in Kitakyushu. Dr. Sawada’s research focuses on establishing and implementing a new therapeutic paradigm for the improvement of inflammatory skin diseases through medical treatment in combination with specific lifestyle alterations such as diet, sleep and physical exercise.

Analysis of epigenetic control of IL-23 expression in keratinocytes

Beneficiary: Dr Cord Brakebusch, Professor, Section of Molecular Pathology, BRIC, Department of Biomedical Sciences, University of Copenhagen

 

Donation: DKK 2,140,000

 

This study seeks new targets to reduce the formation of psoriatic lesions. A novel epigenetic mechanism, which is known to induce IL-23 in psoriasis, is also found in non-lesioned skin and may hold promise.

 

Psoriasis is a chronic inflammatory skin disease that involves a complex crosstalk between immune cells and skin cells (keratinocytes). While the etiology of psoriasis is basically unknown, many researchers have gauged the elements of this crosstalk – in many models. During this work, they have shown that there are multiple different, yet intertwining mechanisms underlying the disease.

 

One is that monoclonal antibodies that target the IL-23/IL-17 immune axis have demonstrated impressive clinical efficacy in patients with moderate-severe psoriasis. There are however, still many missing pieces of the puzzle to fully understand how this disease initiates and develops.

 

Dr Cord Brakebusch’s team has demonstrated that keratinocyte-derived IL-23 is sufficient to cause chronic skin inflammation in mice. Furthermore, they have elucidated an epigenetic mechanism which controls IL-23 expression and it is explained that the epigenetic control mechanism has been shown not just in active psoriasis lesions, but also, albeit to a lesser extent, in normal-appearing skin of psoriasis patients.

 

This suggests that the epigenetic alterations might precede the development of psoriasis lesions, and the team now wants to identify and validate targets for small molecule drugs that may prevent excessive IL-23 expression by keratinocytes through this epigenetic mechanism.

 

As a long-term goal for the study and its potential findings Dr Brakebusch and his team hope that topically administrated small molecular weight inhibitors could prevent excessive IL-23 production by keratinocytes – and ultimately aim at reducing the formation of psoriatic lesions.

International Project on the Global Epidemiology of Psoriasis: Development of the Global Psoriasis Atlas

Beneficiaries: Darren Ashcroft, Professor of Pharmacoepidemiology, The University of Manchester, UK, Chris Griffiths, Professor of Dermatology, Head of Dermatology Research Centre, University of Manchester, UK, & Matthias Augustin, MD, Professor and Director, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg, Germany

 

Donation: DKK 6,370,000

 

The LEO Foundation supports the project “International Project on the Global Epidemiology of Psoriasis: Development of the Global Psoriasis Atlas”.

 

The atlas (GPA) will be a seminal work with focus on epidemiological research that will allow researchers and medical practitioners to compare incidence and prevalence of psoriasis between populations in different countries and thus yield a global ‘picture’ of the disease burden of psoriasis

 

The work with the GPA is done in a project group with three of the world’s leading international dermatology organisations: International League of Dermatological Societies (ILDS), a global organisation representing 148 dermatological societies worldwide; International Psoriasis Council (IPC), a not-for-profit organisation comprising leading international psoriasis experts dedicated to advancing knowledge about psoriasis and enhancing care of the disease; and the International Federation of Psoriasis Associations (IFPA), a not-for-profit organisation representing psoriasis patients worldwide.

 

The mission of the GPA is to provide the common benchmark on the complete burden of psoriasis in all countries and regions throughout the world. The GPA will leverage existing data from publications and registries – and additional studies will be commissioned when gaps are identified.

 

The GPA is a long-term project that seeks to drive continuous improvement in the understanding of psoriasis and to uncover how it affects both the individual and society at large – and will as such play an important part of the overall quest to support research that will someday help researchers find a cause and a cure for psoriasis.

LEO Foundation SPARK grants at Stanford

Beneficiary: Kevin Grimes, Director, SPARK Programme, Associate Professor, Chemical and Systems Biology, Stanford University, California, USA

 

Donation: DKK 4,500,000

 

Bridging the gap between early research and clinical development is a challenging endeavour. There is an inherent risk that early-stage programs will fail during development, no matter how promising the science is.

 

Such nascent programs are unlikely to attract interest from industry until they have reached significant milestones, and very little funding is available from the NIH, foundations, or private enterprise for this critical transition.

 

The LEO Foundation SPARK donations at Stanford will help incubate and accelerate dermatology projects. SPARK is a unique partnership between university and industry targeted advancement of Stanford research towards development of new breakthrough therapies. SPARK provides access to specialised knowledge and technical expertise regarding drug and diagnostic development, dedicated core laboratory facilities, and sources of funding to support translational efforts.

 

The donations will be awarded as a supplement to the existing suite of support and funding from Stanford and will ensure that as many as 15 Stanford dermatology projects will be progressed towards human proof of concept.

 

It is expected that the grant will foster a renewed and unique focus on dermatology at Stanford University and enable a larger number of orphan drug research projects to reach actual clinical development.

 

The grant from the LEO Foundation is paid out in three equal portions in 2016, 2017 and 2018.

 

Learn more about the SPARK Program at Stanford University here.

Epithelial Differentiation and Keratinization Gordon Research Conference (GRC) and Gordon Research Seminar (GRS)

Beneficiaries: Prof. Catharina (Carien) Maria Niessen, Department of Dermatology, University of Cologne, Germany; and Brenda Figueroa, Gordon Research Conferences, West Kingston, Rhode Island, USA

 

Donation: DKK 149,099

 

The 2017 Gordon Research Conference on Epithelial Differentiation and Keratinization (GRC-EDK), to be held May 6-12 in Italy, is the premier international meeting in epithelial biology.

 

It has been held biennially since 1979 with attendance from leading epithelial biology researchers, leaders from other fields, and early career scientists with innovative and exciting research programs to present and promote the latest conceptual, translational and technological advances in epithelial biology.

 

Today, the meetings take on stem cell biology, regenerative medicine, inflammatory skin diseases, skin cancer, epigenetics and global genomics, and the program moreover explores developments in gene therapy, genome organisation, cell competition, stress responses as well as cutting edge advances in intravital imaging.

 

A third of the speakers are from outside the area in order to fuel new concepts and promote discussion of novel ideas, and more than a third of the oral presentations come from submitted abstracts to accommodate late breaking exciting stories and ensure speaking opportunities for young investigators.

 

To promote collaboration between academic medicine and industry the meeting also invites speakers from biotech and other academic scientists with strong industrial ties. Finally, the meeting will continue the commitment to trainee mentorship, including a career mentoring panel discussion with special emphases on careers in academia versus industry, and the importance of diversity within science.

 

Link to the meeting homepage.

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

Beneficiaries: 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

 

Donation: 9,980,000 DKK

 

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

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

 

Donation: 2,000,000 DKK

 

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

Beneficiary: Prashiela Manga, Ph.D., Associate Professor Dermatology and Cell Biology,

New York University School of Medicine, USA

 

Donation: 5,037,192 DKK

 

Vitiligo, an acquired disease in which pigment cells (melanocytes) of the skin are destroyed leading to de-pigmented patches on the skin, affects 1-2% of people worldwide. On top of depriving the skin of its important photo-protection, vitiligo has a significant impact on the physical and mental health of those afflicted.

 

The stigma is compounded by the early age of onset, typically in the first two decades of life, and has a significant negative impact on quality of life of those afflicted, diminishing their ability to find employment and partners.

 

One study has found sufferers of vitiligo to be embarrassed by their appearance and also uncomfortable socialising, leading to severe depression in some cases, and in rare instances, to suicide.

 

The etiology of vitiligo is poorly understood and hinders the development of effective and long-lasting therapies. It is, however, thought to occur in genetically susceptible individuals who are exposed to an environmental trigger that induces oxidative stress and cell death in the melanocytes.

 

Dr. Manga’s exciting study purports to investigate various disease pathways and improve the understanding of the pathobiology of vitiligo.

 

The study may also identify novel targets and agents that can be used in the treatment of this disfiguring disease. Of particular importance is that these therapies may be useful in the treatment of the active disease.

Donations and beneficiaries 2015

Click on the title of the individual project to unfold.

Classification of Actinic Keratoses, identifying and quantifying a novel objective method

Beneficiaries: Ida Marie Heerfordt & Hans Christian Wulf of Bispebjerg University Hospital in Copenhagen, Denmark

 

Donation: DKK 456,169

 

There is a significant clinical need for a more objective and reproducible assessment of AK thickness, severity either in different classes or even better as a continuum. Furthermore it would be valuable to link such assessment with histology and if feasible link with risk of progression as well as potential response to treatment.

 

The methods to be used by Ida Marie Heerfordt and Hans Christian Wulf of Bispebjerg University Hospital in Copenhagen, Denmark, will be to test various diagnostics (measuring skin capacitance, resistance, etc.) and link to clinical presentation, objective measurement of thickness, using a new scale tool and histology.

 

Publication:

http://www.nature.com/articles/srep33952

Harmonizing Outcome Measure for Eczema (HOME)

Beneficiary: The HOME Group

 

Donation: DKK 310,000

 

Despite the high burden of atopic eczema, evidence-based clinical care and decision-making (i.e. comparison of treatment results) is currently limited by the use of multiple un-validated outcome measures (i.e. disease severity scales).

 

In response to this situation, the HOME initiative was formed in 2008, among other to: facilitate an international, multi-disciplinary consensus on core outcome measures to be included in all eczema trials and clinical record keeping.

 

The HOME initiative is an international group working together to agree on core outcome measures for atopic eczema clinical trials. Participation in HOME is open to anyone with an interest in outcomes for atopic eczema. Further information can be found via….

 

www.nottingham.ac.uk/homeforeczema/index.aspx

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

Beneficiary: Associate Professor Kiarash Khosrotehrani, University of Queensland, Australia

 

Donation: AUD 268,239

 

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

Beneficiary: Associate Professor Kiarash Khosrotehrani, University of Queensland, Australia

 

Donation: AUD 415,386

 

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.

International Eczema Council

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

 

Donation: DKK 340,000

 

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.

Young Scientists

Beneficiary: Mikkel Bohm, Young Scientists (Astra)

 

Donation: DKK 3,000,000

 

The talent competition, Young Scientists, is developing talents in both kids and young people in science.

 

It is believed that science is a powerful tool to understand and change the world for the better. The competition’s aim is to contribute to society in a meaningful way by inspiring a new generation and giving them engaging experiences with science.

 

The LEO Foundation has found this work important and supports the competition over 3 years.

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

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

 

Donation: DKK 3,564,000

 

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.

LEO Pharma Research Foundation Award Symposium

Beneficiary: LEO Pharma Research Foundation

 

Donation: EUR 120,000

 

The LEO Pharma Research Foundation (LPRF) has supported research within medicine, chemistry, biology and pharmacy throughout the years. The LEO Pharma Research Foundation is separate from the LEO Foundation, as well as the rest of LEO Pharma, and has its own board.

 

Every year, LPRF presents gold and silver awards to talented and committed young researchers in recognition of their exceptional contribution to science. Candidates are selected in association with the European Society for Dermatological Research (ESDR).

 

The LEO Foundation sponsors LPRF’s award symposium, which takes place at ESDR’s Annual General Meeting and typically features scientific presentations from the two award winners and a keynote speaker.

 

ESDR homepage

LEO Foundation Center for Cutaneous Drug Delivery

Beneficiary: Department of Pharmacy, University of Copenhagen, Denmark

 

Donation: DKK 40,000,000

 

Understanding how drugs interact with skin has long been a challenge within pharmaceutical research. Now, a new center at the Department of Pharmacy, UCPH, is set to become an international lighthouse in this research area, supported by a DKK 40 million grant from the LEO Foundation.

 

The LEO Foundation Center for Cutaneous Drug Delivery will form the basis of new research on skin and drugs. Behind the project is the Department of Pharmacy at the University of Copenhagen, where the center will also be located. The Director of the new center, Martin Malmsten, was formerly Head of Research at Uppsala University.

 

“I hope to contribute with my experience and thus help motivate and inspire colleagues and employees, enabling us to provide the best possible results. At the same time, I look forward to becoming part of the University of Copenhagen, where they have been very willing to prioritize strategic focus areas. The new center offers great and long-term opportunities for making an impact on international research and I’m happy to be part of this initiative, which will lift research in a very exciting area,” says Martin Malmsten.

 

The LEO Foundation Center for Cutaneous Drug Delivery will conduct research on what happens in and on the skin when we apply drugs. There will be a particular focus on the physical-chemical aspects of the interaction between skin and drugs, which is important to the development of new drugs. This will hopefully help optimize the drug properties and allow for maximum utilization while simultaneously minimizing side effects.

 

“Our new center meets a huge demand for understanding how drugs interact with skin. With a strong team of highly qualified researchers, we will set new standards for research in the field of dermatology and I’m both proud and grateful that this grant from the LEO Foundation has helped us attract new and strong forces to UCPH. This new strategic effort will benefit patients as well as society in general,” says Dean Ulla Wewer from the Department of Health and Medical Sciences at the University of Copenhagen.

 

Generating new knowledge while also providing a space for innovative research methods and new analytical technologies is what the center aims for. The LEO Foundation has backed the center with a grant of DKK 40 million over the next ten years, which in itself is quite remarkable.

 

“We’re very happy to support this important initiative and the grant of DKK 40 million over the next ten years is the single largest grant the foundation has ever awarded. What’s more important, however, is the fact that we are quite convinced that the center with its strong team of researchers has the potential to become a global powerhouse in terms of research on the dynamic interaction between drugs and skin,” says Lars Olsen, Chairman of the LEO Foundation.

Donations and beneficiaries 2014

Click on the title of the individual project to unfold.

Psoriasis in children

Beneficiary: Professor Lone Skov, Department of Dermato-Allergology, Gentofte Hospital, Denmark

 

Donation: DKK 4,500,000

 

Psoriasis is a chronic inflammatory skin condition with a prevalence of 2-3% in northern Europe. While considerable research exists on adults with psoriasis, there is little research on the condition in children. Identifying key factors associated with psoriasis in childhood may lead to more effective control and possibly even prevention of the condition.

 

The study aims to determine environmental and genetic risk factors relating to the development of psoriasis in children, the nature of stress related to the child and family, and quality of life. The project also aims to determine the link with risk factors of co-morbidity and the effect of early intensive treatment.

 

The study is led by Professor Lone Skov, Department of Dermato-Allergology, Gentofte Hospital, Denmark. The team will explore the following hypotheses:

  • Risk factors for early onset of psoriasis can be predicted
  • Early debut of psoriasis has a significant impact on quality of life and individual and family-related stress
  • Early intensive treatment leads to remission
  • There is already an increased risk of co-morbidity in children with psoriasis
  • Age at debut, risk factors and co-morbidity are related
    to the genetic risk.

 

The study offers a unique possibility to access data from children with psoriasis shortly after diagnosis, which in turn can pave the way for new and improved tools for assessing the impact of the condition on quality of life in a well-controlled study design.

Donations and beneficiaries 2013

Click on the title of the individual project to unfold.

Identification and Characterization of Key Itch Mediators and Receptors in Human Pruitus

Beneficiary: Professor Martin Steinhoff, University of California San Francisco, CA, USA

 

Donation: USD 388,225 

 

Itch is probably the most common symptom in dermatology and it is associated with a significant impact on the patient’s life.

 

A team led by Professor Martin Steinhoff, University of California San Francisco, has set out to develop novel targeted therapies for chronic itch in humans.

 

Besides the lesional and non-lesional as compared to healthy skin, the project team will also identify critical itch mediators and/or receptors that are expressed (and activated) in human dorsal root ganglion (DRG) and spinal cord tissue. To address this, mediators will be identified as well as receptors associated with human itch, and thereby the team will be able to define “biomarkers” for the different pruritic human diseases.

 

The project will be the first-of-a-kind study to analyse the expression and distribution of key itch mediators and receptors in human skin, human DRG and human spinal cord, and will therefore provide a significant basis for future translational research that targets these mediators/receptors in the different subtypes of itch.

 

Moreover, it is the first time that it will be tested whether several new itch pathways that have been described in murine skin models are relevant, i.e. can be translated, in human disease state.

Care for chronic skin diseases with a patient-centric approach

Beneficiary: Professor Lieve Brochez, University of Ghent, Belgium

 

Donation: EUR 330,000

 

Skin cancer is currently the most frequent type of cancer. At present, life-time risk is estimated at one in six and, with an ageing population, this is expected to increase even more. It is assumed that early detection allows better cure rates and more cost-effective treatment, and skin cancer thus seems suitable for screening initiatives. However, questions remain about the cost–benefit ratio.

 

This study is led by Professor Lieve Brochez of the University of Ghent, Belgium. It aims to calculate the actual cost of skin cancer in Belgium, the expected cost with an ageing population and how much early detection of skin cancer could affect these costs.

 

The team will use the results to develop an internationally applicable health-economic model. The model will allow other European countries to use local data, enabling data to be compared across Europe.

 

Secondly, the study will evaluate a new skin cancer screening approach to compare the yield of this type of screening to the yield of systematic screening in an asymptomatic population within a well-defined population.

 

Quality of life will be assessed for all screened persons with skin cancer and/or actinic keratosis in order to generate patient-centric data to evaluate the burden of skin cancer.

Skin Cancer Screening Education Study

Beneficiaries: Professor Dr Eckhard W. Breitbart & Dr Rüdiger Greinert from the Association of Dermatological Prevention, Hamburg, and the Centre of Dermatology, Buxtehude, Germany

 

Donation: EUR 822,880

 

The Skin Cancer Screening Education Study (SCSES) is an interventional study in Canada to evaluate training of primary-care physicians in skin cancer screening (SCS) with regard to screening outcomes for melanoma and non-melanoma skin cancer.

 

The study, led by Professor Dr Eckhard W. Breitbart and Dr Rüdiger Greinert from the Association of Dermatological Prevention, Hamburg, and the Centre of Dermatology, Buxtehude, both in Germany, will compare screening outcomes for an intervention region with SCS training to screening outcomes for a control region with no training.

 

The SCS training is based on the German SCS training, which forms part of the German skin cancer screening programme. The results of the SCREEN project, which was led by Dr Breitbart, provide the strongest scientific evidence to date that population-based skin cancer screening can be effective. This new study will evaluate clinical and epidemiological screening outcomes as well as educational outcomes. Data on potential risks associated with skin cancer screening will also be obtained.

 

Study results will be published in international publications and presented to the scientific community, public health experts and policymakers at European and international conferences, at roundtables of the European Parliament and national parliaments, and in health committees in the study countries, which include Canada.

Defining the skin and blood biomarkers of pediatric atopic dermatitis

Beneficiary: Dr. Emma Guttman, MD, PhD, Associate Professor of Dermatology, Director Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine, Mount Sinai, New York, NY, USA

 

Donation: EUR 1,046,400

 

Despite considerable impact on quality of life, atopic dermatitis, or eczema, has not been studied extensively in children although as many as one in five experience the condition. Atopic dermatitis, or eczema, is a chronic skin condition, characterised by itching and inflammation, and frequently occurs in people who have other allergic conditions, such as asthma and hay fever.

 

Dr. Guttman has set out to define the skin and blood biomarkers of atopic dermatitis in children. She and her team will investigate how skin biomarkers compare to disease activity, epidermal barrier function and known biomarkers in adults with atopic dermatitis. They will also investigate whether blood biomarkers could offer a less invasive way to monitor skin changes than a skin biopsy, which can be difficult to perform in children.

 

With better knowledge of what causes atopic dermatitis in children, the researchers hope to develop more targeted therapies for the disorder as well as for other atopic conditions, such as asthma and hay fever. Together, these three disorders form an “atopic triad”.

 

Publications:

 

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

J Allergy Clin Immunol. 2015 Oct; 136(4): 941–951.e3.

 

Early-Onset Pediatric Atopic Dermatitis Is TH2 but Also TH17 Polarized in Skin

J Allergy Clin Immunol 138 (6), 1639-1651. 2016 Sep 23.

 

Alterations in B-cell subsets in pediatric patients with early atopic dermatitis

J Allergy Clin Immunol. 2016 Dec 10 pii: S0091-6749(16)31452-X

 

Accelerated T-cell activation and differentiation of polar subsets characterizes early atopic dermatitis development

J Allergy Clin Immunol. 2016 Nov;138(5):1473-1477.e5

 

An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis.

J Allergy Clin Immunol. 2017 Jan;139(1):152-165

Donations and beneficiaries 2012

Click on the title of the individual project to unfold.

Depletion, UV Exposure and Relation between Ozone and Skin Cancer

Beneficiary: Dr. Harry Slaper, Laboratory for Radiation Research, RIVM, Holland

 

Donation: DKK 200,000

 

Dr. Harry Slaper, Laboratory for Radiation Research, RIVM, Holland, has developed a unique model, the AMOUR 2.0, for relating ozone depletion scenarios and UV to changes in skin cancer incidence (melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). This model has been used since 2008 as a reference for other researchers in Europe.

 

The model, however, does not factor in age. Apart from cumulated UV Radiation, age is the major risk factor for the development of Non Melanoma Skin Cancer (NMSC), and an ageing population will contribute to the increasing incidence of NMSCs.

 

The LEO Foundation has funded a development of the model to also incorporate the effects of population aging in Europe in order to obtain a more precise picture of the projected incidence of NMSC in Europe.

 

Based on the Dutch Cancer registry and the enhanced model, then, Dr. Slaper has estimated age and gender specific incidence rates, incorporated them into the model as well as UN Population forecasts to forecast the incidence of NMSC in Europe and the contribution of both cumulated UV radiation and age and gender.

 

The results are expected to play a key role in raising awareness among decision makers in the health care sector on the increasing incidences of non-melanoma skin cancer, an awareness which will also benefit patients as the long-term aim is to increase the political prioritisation of non-melanoma skin cancer.

Phenotyping itch in atopic eczema and psoriasis patients

Beneficiary: Dr Gil Yosipovitch, MD, Professor of the Department of Dermatology at Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

 

Donation: EUR 264,874

 

The LEO Foundation is supporting another project that investigates
itching and may also pave the way for new anti-itch treatments.

 

The study is led by Dr Gil Yosipovitch, MD, Professor of the Department of Dermatology at Wake Forest School of Medicine, Winston-Salem, North Carolina, USA, and seeks to investigate aspects of itching in patients with atopic dermatitis and psoriasis.

 

Itching affects millions of people worldwide and represents a significant medical challenge as no mechanism-specific treatments are currently available. The genetic aspects of itching in chronic pruritic conditions such as atopic dermatitis and psoriasis are also rather under-investigated.

 

Dr Gil Yosipovitch will examine the expression of genes, neuropeptides and other itch-specific mediators specifically implicated in atopic dermatitis and psoriasis in comparison to healthy controls.

 

The exploration of this area may hold good news for patients, as the findings may be useful in developing new anti-itch treatments.

Psoriasis and cardiovascular co-morbidity – funding of an overview committee

Beneficiary: Professor Christopher Griffiths, Faculty of Medical and Human Sciences, University of Manchester, UK

 

Donation: DKK 900,000

 

The background to this project – establishing and operating a multidisciplinary international scientific committee on psoriasis and cardiovascular disease (CVD) – is the increased risk of cardiovascular disease and related mortality amongst psoriasis patients.

 

Research investigating the interface between the two conditions – from epidemiological studies to basic experimental research – may prove key to improving the overall care of psoriasis patients.

 

Chaired by Professor Christopher Griffiths from the Faculty of Medical and Human Sciences at the University of Manchester in the UK, the committee consists of three dermatologists and three cardiologists, with at least one of each based in the USA.

 

The committee’s work focuses on:

  • How scientific understanding can be improved through new research initiatives
  • Building a consensus on biomarkers in research
  • The potential relationships between biomarkers and clinical results and the benefits for patients
  • Areas of particular interest for further research
  • Investigation of cardiovascular side-effects in clinical development projects.

Psoriasis and cardiovascular co-morbidity – epidemiological and experimental studies

Beneficiary: Dr Peter Riis Hansen, Department of Cardiology P, Gentofte Hospital, Denmark

 

Donation: DKK 4,200,000

 

Psoriasis patients have increased risk of cardiovascular disease (CVD), which still carries high morbidity and mortality in western societies, and is increasing dramatically in the emerging economies.

 

Consequently, research directed at the interface between psoriasis and CVD, from the level of epidemiological studies to basic experimental research, is of paramount importance in order to improve overall care for psoriasis patients, as well as supporting the need to seek help to receive treatment.

 

A research project led by Dr Peter Riis Hansen, Gentofte Hospital,
Department of Cardiology P, Denmark, will help to:

  • Inform and motivate dermatologists to play a pivotal role in screening and helping patients with psoriasis to prevent an increased risk of CVD
  • Motivate patients with psoriasis to, firstly, seek treatment and assessment of their CVD risk and, secondly, improve treatment of psoriasis to reduce the overall immune activation
  • Establish a murine model of psoriasis and CVD that is suitable for mechanistic studies and preclinical drug evaluation
  • Identify new markers of psoriasis and/or CVD activity that may be relevant for clinical use.

 

Publications:

 

Khalid U et al. Psoriasis and new-onset diabetes: a Danish nationwide cohort study. Diabetes Care 2013;6:2404-7

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714512/

 

Khalid U et al. Psoriasis and risk of heart failure: a nation-wide cohort study. Eur J Heart Fail 2014;16:743-8

http://www.ncbi.nlm.nih.gov/pubmed/24903077

 

Khalid U et al. Sarcoidosis in patients with psoriasis: a population-based cohort study. PLoS ONE 2014;9(10)e109632

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186869

 

Khalid U et al. Increased risk of aortic valve stenosis in patients with psoriasis: A nation-wide cohort study. Eur Heart J 2015;36:2177-83

http://eurheartj.oxfordjournals.org/content/36/32/2177.long

 

Khalid U et al. A nationwide study of the risk of abdominal aortic aneurysms in patients with psoriasis

http://atvb.ahajournals.org/content/36/5/1043.long

 

Madsen M et al. Effects of TPA-induced experimental psoriasis-like skin inflammation in atherosclerosis-prone apoE knock-out mice. BMC Dermatology 2015

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940745

Epidemiology of eczema disease in Denmark

Beneficiaries: Professor Torkil Menné & Professor Jeanne Duus Johansen, Gentofte Hospital, Denmark

 

Donation: DKK 2,828,000

 

The project involves several research groups at Gentofte Hospital in Copenhagen and is headed by Professor Torkil Menné and Professor Jeanne Duus Johansen.

 

The work aims to shed more light on the incidence of eczema in the general population and pave the way for improved prevention and treatment.

 

Eczema is the most prevalent of the skin disorders. It is not only one of the most common childhood diseases, but also a typical occupational disease, making it one of the most widespread diseases in the overall population. Eczema also results in substantial costs and loss of quality of life for patients.

 

Despite the disease prevalence, there is a shortage of data and research on eczema in the general population.

 

‘This project, which draws on a number of databases and disease registries unique to Denmark, aims to produce a detailed picture of the clinical and sociodemographic aspects of eczema in both the general population and the patient population.

 

Its specific aims are:

  • To describe the consequences of eczema in terms of health care, education and employment, and the development of co-morbidities
  • To explore the genetics behind eczema and its
    consequences.

 

Publications:

Anatomical patterns of dermatitis in adult filaggrin mutation carriers

J Am Acad Dermatol. 2015 Mar;72(3):440-8. doi: 10.1016/j.jaad.2015.01.001. Epub 2015 Feb 7

 

Predictive factors of self-reported hand eczema in adult Danes – a population based cohort study with 5 year follow-up

Br J Dermatol. 2016 Aug;175(2):287-95. doi: 10.1111/bjd.14476. Epub 2016 May 24

 

Health-related quality of life in adult dermatitis patients stratified by filaggrin genotype

Contact Dermatitis. 2017 Mar;76(3): 167-177. doi: 10.1111/cod.12731. Epub 2016 Dec 16 

 

Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry-based study assessing risk of disability pension

Contact Dermatitis. 2017 Aug;77(2):95-105. doi: 10.1111/cod.12786. Epub 2017 Apr 20

The LEO Foundation Scholarship for Dermatological Research

Beneficiary: scholarship programme

 

Donation: DKK 2,200,000

 

The LEO Foundation Scholarship for Dermatological Research aims to strengthen research collaboration within the field of skin cancer between Australia and Denmark by supporting training of and research by young scientists.

 

One scholarship is offered annually on behalf of the LEO Foundation, alternating between Australia and Denmark.

 

A candidate from Australia travels to work within a Danish tertiary institution and a Danish student is selected with a view to joining an Australian campus.

 

The funds received may be used as part of an ongoing PhD project or for postdoctoral research. The funds must in part support a research/educational stay in Australia of at least six months for the Danish student.

 

Publications:

Automated detection of actinic keratoses in clinical photographs

Hames SC, Sinnya S, Tan JM, Morze C, Sahebian A, Soyer HP, Prow TW.

PLoS One. 2015 Jan 23;10(1):e0112447. doi: 10.1371/journal.pone.0112447. eCollection 2015

 

Counting actinic keratosis – is photographic assessment a reliable alternative to physical examinations in clinical trials?

Sinnya S, O’Rourke P, Ballard E, Tan JM, Morze C, Sahebian A, Hames SC, Prow TW, Green AC, Soyer HP.

Acta Derm Venerol. 2015 May;95(5):604-5. doi: 10.2340/00015555-2040. No abstract avaliable

 

The future of keratinocyte skin cancer surveillance: automated image analysis to identify and monitor keratinocyte dysplasia

Hames SC, Prow TW.

Curr Probl Dermatol. 2015;46:77-84. doi: 10.1159/000366540. Epub 2014 Dec 18

 

Automated segmentation of skin strata in reflectance confocal microscopy depth stacks

Hames SC, Ardigò M, Soyer HP, Bradley AP, Prow TW.

PLoS One. 2016 Apr 18;11(4):e10153208. doi: 10.1371/journal.pone.0153208. eCollection 2016.

 

Automated detection of actinic keratoses in clinical photographs

Hames SC, Sinnya S, Tan JM, Morze C, Sahebian A, Soyer HP, Prow TW.

PLoS One. 2015 Jan 23;10(1):e0112447. doi: 10.1371/journal.pone.0112447. eCollection 2015.

 

Counting actinic keratosis – is photographic assessment a reliable alternative to physical examination in clinical trials?

Sinnya S, O’Rourke P, Ballard E, Tan JM, Morze C, Sahebian A, Hames SC, Prow TW, Green AC, Soyer HP.

Acta Derm Venereol. 2015 May;95(5):604-5. doi: 10.2340/00015555-2040. No abstract available.

 

The future of keratinocyte skin cancer surveillance: automated image analysis to identify and monitor keratinocyte dysplasia

Hames SC, Prow TW.

Curr Probl Dermatol. 2015;46:77-84. doi: 10.1159/000366540. Epub 2014 Dec 18

 

Anatomical skin segmentation in reflectance confocal microscopy with weak labels*

Hames SC, Ardigò M, Soyer HP, Bradley AP, Prow TW.

http://ieeexplore.ieee.org/xpls/abs_aa.jsp?arnumber=7371231&tag=1

* This won the Canon Extreme Imaging Competition (DICTA category) prize in late 2015

Donations and beneficiaries 2011

Click on the title of the individual project to unfold.

Skin cancer awareness bus

Beneficiaries: Danish Pharmacy Association & Professor Hans Christian Wulf, Bispebjerg University Hospital, Denmark

 

Donation: DKK 3,042,000

 

The LEO Foundation funded the visit of a “Skin Cancer Awareness Bus” to 30 Danish cities and 15 campsites during the summer of 2011.

 

This initiative was part of a national ‘keep an eye on your skin’ awareness campaign run by the Danish Pharmacy Association with Professor Hans Christian Wulf, Bispebjerg University Hospital, Denmark.

 

The objective of the tour was to improve awareness in the general population of potential health consequences of sun exposure (actinic keratosis (AK) and skin cancer), and to educate on preventive measures linked to skin type as well as to improve current clinical knowledge of skin type and impact of UV radiation.

 

On the bus, visitors could fill out a questionnaire on previous sun exposure, sunburn, AK, skin cancers, etc., as well as receive an assessment of their skin type and a UV photo depicting sun damage in underlying skin.

 

Awareness of AK and skin cancer is currently limited to dermatologists and general practitioners, and patients are mostly unaware of impact and symptoms – and therefore also the notion of self-checking and importance of early diagnosis.

 

The lack of awareness is critical given the continuously growing prevalence of AK, and the growing consensus about perceiving AK as a precursor and an early stage of squamous cell carcinoma.
Questionnaires and skin type data have been linked to each respondent’s PNR (CPR) number, facilitating future research through registry linkage to e.g. the Danish Cancer Registry, National Patient Registry, etc.