Latest Research Grants Announced

Dr Paola Di Meglio, King’s College London

Biological drugs, such as ustekinumab (Stelara®), have a significant positive impact on the lives of people with psoriasis. Nevertheless, these expensive drugs do not work in every individual, and are still prescribed by trial-and-error. This process can be very frustrating for patients, and is not cost-effective for the NHS.

In order to prescribe the best possible drug to each individual with psoriasis, doctors need to be able to categorise people according to specific biological markers (“biomarkers”) that predict the likelihood that the drug will work. The Psoriasis Association-endorsed Psoriasis Stratification to Optimise Relevant Therapy (PSORT) is a multicentre study aimed at identifying biomarkers predictive of response to biologic drugs.

As part of PSORT, we are looking specifically at the white blood cells as potential predictive biomarkers. We aim to analyse cells already obtained from the blood of patients receiving ustekinumab, and measure a number of biological markers associated with them. Moreover, we will apply mathematical and statistical techniques to understand whether any of the biological markers measured can predict whether or not each individual patient will do well on ustekinumab.

Our findings will eventually be integrated with other datasets currently produced by PSORT (e.g. genetic data) to produce a clinically useful tool (“stratifier”) to guide psoriasis management, for the benefit of people with psoriasis, and to reduce costs for the NHS.

Dr Daniele Bergamaschi, Queen Mary University of London

Autophagy is a detox process naturally supporting the epidermis in cleansing and replacing damaged cells in exchange of energy. This is a crucial mechanism as one of the main skin functions is to protect the organism from UV exposure and infections.

When keratinocytes are surrounded by inflammatory cells for a prolonged time, they lose their ability to detox and replace damaged cells. Inflamed skin cells release toxic substances (Reactive Oxygen Species) which reduce their healthy ability to purify themselves thus preventing them to transform their shape and size. We have recently shown that when skin cells detox, they also gradually lose their nucleus with a process called Nucleophagy. This mechanism is not correctly functioning in the few skin diseases including psoriasis.

In this project we will further determine the effects of inflammation on the autophagy machinery in healthy human and psoriatic epidermis and will establish the consequences of having a deregulated form of this metabolic process. This will be achieved by measuring where the protein involved in the autophagy process of the skin are expressed and whether they are correctly functioning. As a model we will use cell lines isolated from normal and psoriatic skin and with them we will also reconstruct in 3D psoriatic-like artificial skin to perform experiments of drug treatment.

This research project will significantly improve our understanding of how this detox metabolic mechanism can impact on development of psoriasis and may lead to the identification of novel therapeutic and preventative targets for this common skin condition.

Dr Parastoo Babakinejad, Royal Victoria Hospital, Newcastle

Patients with psoriasis appear to have higher rates of liver fibrosis in comparison to the general population. The prevalence of liver fibrosis in the psoriasis population in the UK has not been defined. The higher rates of risk factors for liver fibrosis such as obesity, alcohol and diabetes are important; however there have been concerns that methotrexate can contribute to liver fibrosis. Despite the increasing importance of biologic therapies, methotrexate remains the most commonly used systemic agent in the UK. The majority of patients needing systemic therapy will try methotrexate first as per NICE guidance. 

This study aims to investigate the prevalence of liver fibrosis in a group of patients with psoriasis by measuring liver stiffness measurement (LSM) using Transient Elastography. The cumulative methotrexate dose in addition to other important factors including BMI, waist circumference and alcohol intake will be recorded. A univariate analysis will be performed to investigate the relationship between all measured factors and LSM. The relationship between the cumulative dose of Methotrexate and liver fibrosis will be addressed.

The ultimate goal is to use the prevalence data to perform a power calculation to determine the number of participants required to conduct a study to determine which factors can predict the risk of liver fibrosis and whether or not methotrexate is an independent risk factor for liver fibrosis in patients with psoriasis. Using this data a risk prediction model can be built to allow optimal and safe prescribing of methotrexate.

Ms Ella Guest, University of the West of England

The transient and unpredictable nature of psoriasis can make it a difficult condition to manage. In addition to physical symptoms such as pain, itching, and discomfort, which are often visible to others, psoriasis can also impact considerably on psychosocial wellbeing. Although effective treatments for physical symptoms are available, evidence suggests that many patients find it difficult to adhere to their treatment regime, making them more susceptible to distressing flare-ups. Concurrently, previous research has found patients to perceive current information and support to be insufficient to help them effectively manage their condition. Compared to other areas of healthcare, qualitative research is relatively scarce, with little specific investigation into how people manage flare-ups. 

In the recent priority-setting exercise by the Psoriasis Association, the list of top 10 research questions included: “What’s the best way to treat sudden flare-ups of psoriasis?” The proposed study will investigate the impact of psoriasis flare-ups on patients’ psychological wellbeing and life engagement, barriers and facilitators to managing flare-ups, and patients’ information and support needs using an in-depth qualitative approach. Individual semi-structured telephone interviews will be conducted with approximately 30 individuals living with psoriasis, aged 16 years+. 

The findings will provide guidance as to what types of support may be most helpful, when, and for whom; identify how information and signposting by health professionals could be improved; and provide practical suggestions for supporting treatment adherence, allowing individuals to assert more control over their condition, reduce their likelihood of developing co-morbid disorders, and support them to cope with flare-ups.