PACT: Personalizing Acne Treatment Using Skin Microbiota Transplantation

Grantee: Holger Brüggemann, Associate Professor, Aarhus University

Amount: DKK 2,179,800

Grant category: Research grants in open competition

Year: 2021

Geography: Denmark

This project aims to investigate the potential of using bacteria exchange or “microbiome transplant” as a viable treatment option for acne vulgaris.    

Acne vulgaris remains one of the most prevalent skin conditions worldwide affecting close to 10% of the population and impacting the quality of life of millions of people. Multiple factors contribute to acne, including genetics, excess sebum production, colonization of the skin by Cutibacterium acnes and an inflammatory cascade. Current treatments for acne such as retinoids and antibiotics have varied outcomes and side effects. As antibiotic resistance becomes an increasing concern in clinical practice, there is an unmet need for alternative treatment approaches.   

The team have previously identified a range of bacterial strains, isolated from healthy skin, that can selectively inhibit acne-associated Cutibacterium acnes strains. The current project takes a microbiome transplantation approach to acne treatment, utilizing a pre-existing in-house library of more than 1000 bacterial strains and testing their ability to modulate the skin microbiome and reduce acne symptoms in patients with mild-to-moderate acne.  

This project may pave the way for developing a personalized treatment to a very common skin disease while avoiding the issue of antibiotic resistance. 

T-cell – keratinocyte interactions as therapeutic targets in lichenoid and interphase dermatoses

Grantee: Georg Stary, Principal Investigator, Medical University of Vienna

Amount: DKK 3,136,390

Grant category: Research grants in open competition

Year: 2021

Geography: Austria

Summary available soon.

Global serum proteome profiling of hidradenitis suppurativa patients

Grantee: Simon Francis Thomsen, Professor, Head of Department, Department of Dermatology, Bispebjerg Hospital

Amount: DKK 2,257,500

Grant category: Research grants in open competition

Year: 2021

Geography: Denmark

The project aims to better understand the molecular basis of Hidradenitis Suppurativa (HS). HS is a debilitating chronic skin disease characterized by the formation of painful nodules and abscesses predominantly in the armpits, groins, and buttocks. With time, the disease may progress resulting in persisting tunnels in the skin and pronounced scarring. While there are many treatment options for HS, successful management often remains difficult and sometimes elusive – which likely reflects the still incompletely understood pathogenesis.  

Simon Francis Thomsen and his team will approach this by doing a large-scale, prospective study where they determine the protein composition of blood from more than 500 HS patients. They will follow the changes during disease progression (identified as Hurley stage I to III) to identify key biomarkers and signaling pathways specific for the disease.  

The study is a unique translational endeavor which brings together clinical dermatologists with basic scientists to explore and characterize the serum proteome of patients with HS through analysis of blood serum samples obtained at the Department of Dermatology, Bispebjerg Hospital.  

Finding a silver bullet to reduce scarring

Grantee: Yuval Rinkevich, Principal Investigator, Helmholtz Center Munich

Amount: DKK 3,683,525

Grant category: Research grants in open competition

Year: 2021

Geography: Germany

The project aims to investigate the role of the skin fascia (a membrane structure in the skin) and its interplay with a specific type of “scar-inducing” cells to better understand – and subsequently prevent – formation of scars. These scar-inducing cells express a unique gene marker, but the cell biology and biochemistry driving the scar process are still unknown despite wounds being an extensively studied clinical challenge.  

Yuval Rinkevich and his team will use novel whole skin-fascia explants (scar-in-a-dish) along with fluorescent “scar-forming” cells that can be tracked during contracture scar formation using live imaging to understand the dynamics of the scar process. Along with single-cell RNA sequencing this will help reveal the cellular and molecular basis of the process and make way for a knowledge basis for its improvement in human skin.  

In addition, the project will investigate the potential of several FDA approved small molecules for treatment of contracture scars. 

The research has the potential to change our scientific and medical views of wound repair and open new therapeutic avenues to treat a variety of fibrotic skin conditions. 

Positional Information and Repair of Skin Injury

Grantee: Peter Reddien, Professor, Whitehead Institute, Cambridge

Amount: DKK 2,498,235

Grant category: Research grants in open competition

Year: 2021

Geography: USA

Summary available soon.

Developing 1600 nm OCT angiography to quantify severe inflammatory epidermal hyperplasia in atopic dermatitis

Grantee: Stephen Matcher, Professor, University of Sheffield

Amount: DKK 4,197,519

Grant category: Research grants in open competition

Year: 2021

Geography: United Kingdom

The aim of this project is to enable quantification of the effects of treating atopic dermatitis (AD) with new therapies. New therapies have similar effectiveness to steroids but are much more expensive. Thus, there is a need for demonstrated benefits and better long-term safety to persuade healthcare providers to fund them.

Optical coherence tomography (OCT) is an ideal tool to quantify the benefits of new drugs for treating AD, whilst checking that they do not cause skin thinning, which is a risk with long-term use of steroids. OCT is a non-invasive imaging technique that uses laser light to provide ultrasound-like images with higher resolution – and OCT avoids the need to perform painful biopsies.

One problem with the current OCT systems is that if the skin inflammation becomes too high, it becomes difficult to quantify because OCT can only image to depths of around 1 mm. This limited depth penetration can potentially be improved by using a longer wavelength of laser light. With the project, Stephen Matcher will quantify the improvement in OCT image quality when using 1600 nm light rather than the current 1300 nm light.

If successful, the project holds a strong potential for use in both clinical trials and clinical practice with a highly needed more patient-friendly tool for measuring drug efficacy in skin diseases such as atopic dermatitis.

Immunomodulatory porous biomaterials for skin regeneration

Grantee: Philip Scumpia, Assistant Professor, University of California – Los Angeles, CA

Amount: DKK 3,885,333

Grant category: Research grants in open competition

Year: 2021

Geography: USA

This project predicts in situ/local immunomodulatory biomaterials as a novel therapeutic approach to engineer regenerative wound healing and limit scarring.

Local tissue engineering represents a promising approach to regenerate tissue, however, immunologic barriers to restore tissue strength and function must be overcome. In previous studies, Philip Scumpia has shown that by simply inducing an adaptive immune response from a novel synthetic biomaterial that mimics the natural porosity and other characteristics of the skin, it is possible to provide the inductive signals to regenerate hair follicles and sebaceous glands in small murine cutaneous wounds.

In this project, it is proposed to identify the cells and the signals from the innate and adaptive immune system responsible for switching profibrotic signals in the wound environment to regenerative signals. This will be achieved by combining novel, pro-regenerative biomaterial formulations with loss-of-function studies of cells and factors of the immune system. Single-cell RNA-sequencing, multiplexed immunofluorescent microscopy, and bioinformatics analyses will be applied to directly assess biomaterial-to-cell and cell-to-cell interactions at the molecular level.

If successful, the project may help identify key players in regenerative wound healing, which would be of great importance.

Sodium intake and storage in the skin

Grantee: Katrina Abuabara, Associate Professor, University of California – San Francisco, CA

Amount: DKK 3,965,534

Grant category: Research grants in open competition

Year: 2021

Geography: USA

The rapid increase in prevalence of AD suggests that environmental factors play an important role, but which environmental drivers are most important and the mechanism by which they impact AD is unclear. Large epidemiological studies suggest that changing diets are an important contributor. Dietary sodium intake warrants additional investigation because studies have shown high rates of sodium storage in the skin and that high sodium concentrations can trigger inflammatory responses involved in AD.

To study this, Katrina Abuabara will enroll 30 participants and employ a novel Magnetic Resonance Imaging (MRI) technique that has been shown to accurately quantify skin sodium concentration to examine whether a low-sodium diet can decrease skin sodium concentration and improve AD severity. The study presents a strong statistical analysis plan to identify key parameters for a future full-scale clinical trial.

If sodium restriction proves to be beneficial, it could lead to actionable impact on AD patients as a cost-effective, low-risk intervention that could be implemented in low resource settings.

Keratinocyte contributions to inflammatory skin disease – Desmoglein 1 loss as a model

Grantee: Kathleen Green, Professor, Northwestern University - Illinois

Amount: DKK 3,025,870

Grant category: Research grants in open competition

Year: 2020

Geography: USA

The aim of this project is to study how the loss of a cell-cell adhesion protein called Desmoglein 1 helps drive activation of the immune system in inflammatory skin diseases.

The skin’s outermost layer, the epidermis, is made up of closely connected skin cells and plays a critical role in establishing an efficient barrier between the human body and the environment. Failure of this barrier in infectious, inflammatory and genetic skin diseases leads to clinical appearances driven by the interplay between the epidermis and the immune system.

Essential to establishing this epidermal barrier is a member of the desmosomal cadherin family of intercellular adhesion molecules, Desmoglein 1, whose best-known function is to connect neighboring skin cells together.  Professor Green and her team at Northwestern University, along with the group of Dr. Eran Cohen-Barak, Ha’Emek Medical Center Afula, Israel, are studying Desmoglein 1 functions that transcend their roles as ‘cell glue’. Their data suggest that loss of this protein increases immune responses and that the pathways activated are similar to those observed in inflammatory skin diseases like psoriasis.

Dr. Green and her team will use Desmoglein 1 deficient mice and Desmoglein 1 deficient human cells and tissues to determine the extent to which lack of this protein contributes to inflammatory skin diseases and to define molecular pathways that connect Desmoglein 1 to the immune system.

Deciphering the pathogenic immune infiltrate in atopic dermatitis subtypes

Grantee: Patrick Brunner, Associate Professor, Medical University of Vienna

Amount: DKK 3,447,335

Grant category: Research grants in open competition

Year: 2020

Geography: Austria

The aim of this project is to address the challenge that current treatments for atopic dermatitis (AD) only work as long as they are given.  

A subgroup of the so-called tissue-resident memory (Trm) T-cells appears to be absent in healthy controls and in patients, who have outgrown their AD, but is still present at least a year after a successful clinical outcome following treatment with dupilumab.  

Using state-of-the-art single-cell sequencing methods combined with advanced flow cytometry and so-called suction blistering for collecting sample material, the project will characterize the composition of cells and proteins within skin lesions of AD patients. Compared to most other approaches, this multi-omics approach is expected to provide a much more accurate reflection of what is going on in this complex disease which shows considerable heterogeneity from patient to patient.  

The present project is an extension of a project previously supported by the LEO Foundation (LF18098) where Patrick Brunner successfully refined and validated his sample collection methods. The present project may guide future targeted AD treatment approaches in a more personalized and stratified manner and may offer a relatively short way from bench to bedside.