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Psoriasis affects 2-4% of the Western adult population and is a socio-economic burden for patients and society.

Topical drugs are recommended as first-line treatment for mild to moderate psoriasis, but low adherence is a barrier for treatment success.

There is a need for improved patient support for psoriasis patients, which is suggested to improve long-term use of topical drugs.

The project aims to test whether a patient-supporting intervention delivered by healthcare professionals can improve the use of topical drugs.

The intervention design is based on experiences with previous adherence-improving studies consisting of digital support by conducting a systematic literature search and holding focus groups with patients as well as healthcare professionals. The intervention consists of shared decision-making with patients, nurses and doctors, frequent consultations, easy access to healthcare professionals through video or in-office consultations and holding patients accountable for taking the medication.

The intervention will be tested in a randomized controlled trial: during a 1-year period, a group of patients (18-75 years of age) diagnosed with mild-to-moderate psoriasis and treated with topical drugs will be randomized to an intervention (n=65) or non-intervention group (n=65).

The primary outcome will be primary adherence (i.e., rate of filled prescriptions) and secondary outcomes a reduction in the severity of psoriasis and cost-effectiveness. If the intervention can reduce the severity of psoriasis in a significant manner and is cost-effective, there is a potential for a national implementation of the intervention.

Long-term topical application of steroids such as hydrocortisone have severe skin side effects. Here treatments lead to thinning of the outer layer of the skin, reduced production of natural moisturisers and an increased risk of skin ulceration.

We hypothesise that an increased understanding of how hydrocortisone exerts its effect on skin cells will help us understand why hydrocortisone treatment causes these adverse effects and also aid the development of treatments that can bypass these.

Here we propose to take advantage of exciting new methods we have developed, where we can measure how cells behave within the skin and thereby quantify exactly how hydrocortisone affects cell turnover. This analysis will be combined with detailed studies for how hydrocortisone function at the mechanistic level in order to identify potential new therapeutic targets. Such therapies could be used to help patients receiving long-term hydrocortisone treatment.

Staphylococcal bacteria are the most common cause of skin and soft tissue infections (SSTI) and with the rise of methicillin-resistant Staphylococcus aureus (MRSA) minor infections can lead to severe medical conditions.

The increasing antibiotic resistance development demands the search for alternative medicines with differing profiles ranging from prophylactic treatment of small infections to combating life-threatening conditions.

In the present project, we aim to inhibit this quorum sensing through a novel concept and thereby develop pan-staphylococcal inhibitors that are capable of treating the virulence in skin infections without the use of antibiotics.

Targeting the virulence of a bacterial infection rather than the viability of the pathogen represents such an alternative, because it increases the chance of clearance through the human immune system and attenuates disease symptoms while minimizing the risk of emerging resistance.

The expression of virulence factors in Gram-positive bacteria, including staphylococci, is regulated through quorum sensing (QS), which is a mechanism that allows bacteria to change gene expression in response to cell density.

This cell-to-cell communication is mediated by the secretion and detection of molecules termed autoinducing peptides (AIPs).

The survival rate of patients with advanced melanoma has improved in recent years due to the clinical application of immune checkpoint inhibitors, as well as kinase inhibitors in BRAF/RAS-mutated melanoma cases.

However, melanoma remains a fatal diagnosis as a consequence of emerging resistance mechanisms and the absence of reliable biomarkers that identify high-risk tumour subsets, therefore impacting the stratification of these subsets for novel adjuvant therapies.

In the search for novel oncosuppressors that are altered in melanoma, we have found a promising candidate in the protein called AMBRA1. AMBRA1 has a fundamental role in the positive regulation of autophagy – a process which can elicit both pro- and anti-tumorigenic roles. Additionally, AMBRA1 finely modulates other crucial oncogenic processes, such as cell proliferation, cell invasion, and cell death.

Our preliminary research in a mouse model of melanoma has proven Ambra1 to be a crucial oncosuppressor, whose expression has been found highly altered in a number of human melanoma cells. Thus, by applying melanoma cell and mouse models in combination with systems biology approaches and state-of-the-art technologies, we aim to decipher the response of Ambra1-deficient melanomas to the current therapies.

Moreover, we will investigate the role of Ambra1 in regulating lipid metabolism in melanoma, which has recently been shown to profoundly affect its progression. Additionally, our aim is to assess the prognostic relevance of AMBRA1 in human cohorts of melanoma patients and understand whether AMBRA1 expression correlates with disease progression and whether it influences treatment.

Outcomes from this project will pave the way for novel clinical insight into the prognosis and treatment of melanoma patients.

This project is co-supported by a Young Investigator award from the Melanoma Research Alliance (MRA) in the USA of 224,500 USD (https://www.curemelanoma.org/research/grants/).

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.