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

Grantee: Professor Martin Steinhoff, University of California San Francisco

Amount: USD 388,225

Grant category: Research grants in open competition

Year: 2013

Geography: USA

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

Grantee: Professor Lieve Brochez, University of Ghent

Amount: EUR 330,000

Grant category: Research grants in open competition

Year: 2013

Geography: Belgium

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

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

Amount: EUR 822,880

Grant category: Research grants in open competition

Year: 2013

Geography: Germany

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

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

Amount: USD 1,046,400

Grant category: Research grants in open competition

Year: 2013

Geography: USA

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

The LEO Foundation Award 2012 – Silver Award

Grantee: Dr. Andrea Chiricozzi

Amount: DKK 500,000

Grant category: LEO Foundation Awards

Year: 2012

Geography: Italy

Presented to skin immunology specialist Dr. Andrea Chiricozzi at the Department of Dermatology, University of Rome Tor Vergata, Italy.

Chiricozzi’s research focuses on chronic skin inflammation and the pathogenic circuits underlying the formation of skin lesions, particularly in regard to psoriasis and atopic dermatitis. The award will support Chiricozzi’s on-going research into the pathogenic mechanisms in skin disorders and novel therapeutic strategies.

The LEO Foundation Award 2012 – Gold Award

Grantee: David Schrama

Amount: DKK 1,000,000

Grant category: LEO Foundation Awards

Year: 2012

Geography: Austria

Presented to Assistant Professor David Schrama at the Dermatology Department at Graz Medical University, Austria.

Schrama’s research focuses on melanoma biology. His research team currently analyses the impact of genetic diversity among patients and tumours on prognosis and clinical outcome of therapies. In recent years, Schrama’s scientific work has focused on unravelling the biology of another skin cancer; the polyomavirus associated merkel cell carcinoma.

Depletion, UV Exposure and Relation between Ozone and Skin Cancer

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

Amount: DKK 200,000

Grant category: Research grants in open competition

Year: 2012

Geography: Netherlands

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

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

Amount: EUR 264,874

Grant category: Research grants in open competition

Year: 2012

Geography: USA

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.

Publication 

The genetics of chronic itch: gene expression in the skin of atopic dermatitis and psoriasis patients with severe itch

* Nattkemper LA, Tey HL, Valdes-Rodriguez R, Lee H, Mollanazar NK, Albornoz C, Sanders KM, Yosipovitch G, The genetics of chronic itch: gene expression in the skin of atopic dermatitis and psoriasis patients with severe itch, The Journal of Investigative Dermatology (2018), doi: 10.1016/j.jid.2017.12.029.

See article (pdf): Genetics of Chr Itch

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

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

Amount: DKK 900,000

Grant category: Research grants in open competition

Year: 2012

Geography: United Kingdom

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

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

Amount: DKK 4,200,000

Grant category: Research grants in open competition

Year: 2012

Geography: Denmark

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