Research Results

Since 1971, the Psoriasis Association has awarded over two hundred grants thanks to your generous support and fundraising efforts. To view some of the more recent research projects that have been completed, please use the boxes below.

Please note, the projects are dated from when the award was granted, rather than when the project finished.

2014

Investigation of the roles of UV-induced nitric oxide and vitamin D in Narrow-band UVB phototherapy treated psoriasis patients.
Dr Richard Weller - University of Edinburgh

Ultra Violet Phototherapy is one of the most effective treatments for psoriasis, but the mechanism by which it works is not fully understood.

We have previously shown that when ultraviolet hits the skin it releases nitric oxide (NO) gas into the circulation. In this work funded by the Psoriasis Association we were able to show that nitric oxide turns a form of white blood cell known as a T cell into an anti-inflammatory cell called a T-regulatory cell. We showed that these T regulatory cells are able to reduce inflammation and also that they change in a way that makes them more likely to enter the skin. We think that this is probably one of the means by which ultraviolet treatment reduces the inflammation in the skin, which is a hallmark of psoriasis. We plan to investigate this further as understanding how UV produces benefit offers the opportunity to improve the effectiveness of phototherapy or maybe even to develop a new treatments using the NO pathway without the need to attend hospital for phototherapy.

2013

PhD Studentship - An investigation into genetic factors which discriminate psoriasis from psoriatic arthritis
Eftychia Bellou, supervised by Professor Richard Warren – University of Manchester

Approximately 1 in 3 people with psoriasis develop psoriatic arthritis (PsA), an inflammatory arthritis that causes pain, swelling and joint stiffness. Like psoriasis, PsA occurs as a result of the immune system mistakenly attacking healthy tissue, but it's not clear why some people with psoriasis develop psoriatic arthritis and others do not. However, psoriasis is not only linked to the joints,  it is also known to be related to the presence of various other co-exisiting morbidities including cardiovascular disorders, depression, and diabetes, leading to a diminished health-related quality of life.

This study aims to search  genetic and environmental factors such as smoking and obesity that discriminate psoriasis and PsA. Finding predictors of the development of PsA in people with psoriasis will help clinicians better diagnose patients according to their symptoms. They will also be able to intervene early on in the disease process thereby controlling joint damage. Finally, the discovery of specific genes that are responsible for the development of PsA can help in the development of more effective and stratified therapies. Apart from the main direction of this study, an additional objective is to investigate the prevalence of comorbidities with PsA, and psoriasis without arthritis, using the UK Biobank which contains data from approximately half a million people from across the UK.

During the past year a genetic study has been conducted using novel statistical methods and data from other musculoskeletal diseases (such as rheumatoid arthritis, lupus erythematosus, ankylosing spondylitis and juvenile arthritis) in order to identify novel genetic variants associated with PsA and potential genes that are associated with a sub-group of these disorders. The latter can help us understand the common biological pathways underlying PsA and the other musculoskeletal diseases. These diseases were chosen because they have a shared genetic basis with PsA and they could boost the possibilities of finding new genetic variants.

Finally, the project will explore the possibility of whether the risk factors (such as BMI), that were found to be associated with PsA during the epidemiological study earlier on in the project, are causes that could trigger the development of arthritis in patients with psoriasis. This will be investigated using the genetic data that was published by the UK Biobank. In previous epidemiological studies, the co-occurrence of psoriasis/PsA with a number of exposures such as smoking and increased obesity was shown, but this did not provide adequate evidence that these are risk factors for developing psoriasis and PsA. Using genetics rather than measured exposures has many advantages and could shed some light on the causes of the diseases of interest.

PhD Studentship - Functional characterisation of genetic susceptibility to psoriasis
Alicia Lledo Lara, supervised by Professor Julian Knight – Oxford University

The work of this PhD project aimed to build on previous genetic studies to identify the genetic variants that are causing psoriasis and to understand the way they alter the normal functioning of the immune system to lead to psoriasis. In order to answer this question we looked at four cell types from the immune system that have been identified by previous studies to be important in psoriasis. We obtained these cells from people with  and without psoriasis and we looked at how open was the DNA at each position of the genome. The genome, in order to fit inside each of the cells of our body, needs to be tightly packed. When there is the need to read the message contained by a gene, the DNA unwinds and becomes more accessible. As a result, we defined and compared the accessibility of the different regions of the genome in the four cell types from people with and without psoriasis and we found differences at several positions in the genome. The cell type that showed the most differences is called CD8+ and they are seen as the foot soldiers of the immune system, in charge of attacking virus, bacteria or other cell types with various toxic compounds. We also measured the activity of each of the genes of the human genome in the same 4 type of cells and we found that the activity of genes in CD8+ cells were also the most different between people with and without psoriasis. It was very interesting to see that some of the regions that were differently open between the people with psoriasis and people without were located nearby genes whose activity was also altered. For example a gene called GRP56, which is involved in reducing the inflammatory ability of different immune cells, was found to be present in lower amounts in the CD8+ cells of people with psoriasis. This could explain the more powerful response of the immune system that contributes to developing psoriasis.

Measuring  gene activity in the affected and non-affected skin of 3 people with psoriasis discovered several genes for which levels in the two types of skin were different. One of those genes, IFIH1, is regulated by a genetic variant that has been  associated with psoriasis in previous studies. The genetic variant  protects from psoriasis and seems to reduce the activity levels of this gene, IFIH1, which is involved in switching on the inflammatory response and could therefore also be a very interesting gene target for new treatments.

Overall, this research represents a step forward in how to study the function of particular genetic variants in the development of psoriasis. This study not only uses samples taken from people with psoriasis but also has generated different types of data from each of them. This will hopefully help to make complete the jigsaw of the genetic susceptibility in psoriasis and eventually will contribute to improve the quality of life for people with psoriasis through the development of more efficient and effective treatments.

PhD Studentship - Psoriasis and sleep deprivation
Alasdair Henry, supervised by Professor Chris Bundy - University of Manchester

Prior to starting this research, studies examining the extent, characteristics and factors associated with sleep disturbance in people living with psoriasis were relatively scarce. This was identified in study one which  reviewed the literature, finding that current research demonstrated significant variation in the rates of sleep disturbance, limited use of sleep-specific assessment tools, and that current literature is typically of poor quality.

Given the current literature, a comprehensive investigation of sleep in psoriasis was warranted. In study two we showed that sleep disturbance was common, affecting more than 75% of participants. Poor sleep quality and obstructive sleep apnoea (OSA) were associated with more severe psoriasis, and poor sleep quality was independently associated with psychological (thoughts and worries at night, low mood,) and physical variables (itch and body not feeling ready for sleep at night). In addition, short sleep duration and difficulties initiating and maintaining sleep were documented.  Finally, in agreement with other research, this study found an increased likelihood of OSA in those with psoriasis. This study highlighted that sleep disturbance is common in psoriasis, and that it is associated with both psychological and physical variables.

Study three investigated sleep disturbance in people with psoriasis, with a focus on the associated factors identified within study two.. Sleep difficulties appeared to be persistent and present for a number of years. Difficulties were associated with psoriasis-specific features including thoughts and worries about psoriasis and psoriasis symptoms. However, the thought processes (e.g. worry, rumination, uncontrollable thoughts) described were similar to those described in insomnia in general. Coping strategies were limited in their effectiveness at improving sleep, with many exacerbating sleep difficulties. Furthermore, psoriasis flares were  described in the days following poor sleep, which could often negatively feedback on sleep. Importantly, participants reported a lack of attention provided to sleep by healthcare professionals, and that their concerns were often belittled or diminished when seeking help. This study indicated the significant influence persistent sleep disturbance has on the lives of people with psoriasis and that the links between psoriasis and sleep disturbance appear to be bi-directional. 

The primary aim of study four was to examine the relationship between sleep and the next day experience of psoriasis. Results of this study indicated that daytime psoriasis symptoms predicted sleep fragmentation and that pre-sleep arousal predicted  perceptions of sleep. In contrast to the findings of studies two and three, psoriasis symptoms did not emerge as robust predictors of sleep parameters. Nevertheless, relationships between sleep and next-day functioning were evident with both objective and subjective parameters significantly predicting next day fatigue, sleepiness and concentration. Findings from this study suggest that targeting pre-sleep arousal may confer improvements upon sleep and functioning the following day. 

Taken together, the four studies provide a multi-dimensional and detailed understanding of sleep disturbance in psoriasis. Importantly, they highlight psoriasis-specific factors associated with sleep disturbance and document the significant detrimental impact sleep disturbance can have on the lives of those living with psoriasis. Based upon the findings of these studies it seems likely that currently available treatments for sleep disturbance, notably cognitive behavioural therapy for insomnia may be effective at improving sleep and daytime functioning in people with psoriasis.

2011

PhD Studentship - Oxidised lipids and their role in the immunopathology of Psoriasis
Michael Olding, supervised by Dr Tim Millar, Dr Mike Arden-Jones and Professor Eugene Healy – University of Southampton

People with psoriasis have been found to have abnormal levels of lipids in their blood. While these waxy or fatty substances play a number of important roles in the body, abnormal lipid levels are known to be a key factor in other conditions such as heart disease. This project looked at whether different levels of lipids affected inflammation and blood vessel formation, and could therefore be playing a role in psoriasis.

It was found that lipids were important for maintaining immune cell proliferation and supporting new blood vessel formation. In addition, oxidation (the process that makes iron rust) of a lipid called LDL (low density lipoprotein) and the concentration of oxidised-LDL was found to be important in regulating inflammation. While further work is needed to understand how oxidised-LDL causes inflammation, this work may provide the basis for a new drug target to treat psoriasis.
 

PhD Studentship - The Genetic Basis of Pustular Psoriasis and its Overlap with Psoriasis Vulgaris
Dorottya Maria Berki, supervised by Dr Francesca Capon, Professor Richard Trembath and Professor Jonathan Barker -King's College London          

Pustular Psoriasis (PP) is a rare and disabling inflammatory skin disorder that is associated with an increased risk of plaque psoriasis. While mutations in two genes (IL36RN and AP1S3) have been shown to cause PP, less than 30% of people with PP have these mutations. In addition, the main genetic mutation associated with plaque psoriasis has been shown to not to be associated with PP. As a result, the genetic causes of PP and the link with plaque psoriasis remain poorly understood. This project aimed to address this.

In the first part of the project, the possibility that the IL36RN gene may contribute to plaque psoriasis susceptibility was investigated. The results suggested that this important genetic factor of PP does not the increased risk of plaque psoriasis.

Next, the CARD14 gene, which had been previously associated with plaque psoriasis that runs in families, was looked at in people with PP. A mutation was found in a small number of people with PP, predominantly people of Asian descent with PP, which caused constant CARD14 activation.

PhD Studentship - The role of exercise on cardiovascular disease risk in psoriasis
Lisa Auker, supervised by Dr Helen Young, Professor Christopher Griffiths and Dr Lis Cordingley -University of Manchester

People with psoriasis have an increased risk of cardiovascular disease (CVD) and traditional CVD risk factors are highly prevalent in the psoriasis population. We hypothesised that individuals with psoriasis may avoid physical activity, which may contribute to their elevated CVD risk.

The aims of this PhD were to: i) identify the barriers to cardiorespiratory fitness; ii) determine whether physical activity influences arterial stiffness and cardiorespiratory fitness and iii) identify biomarkers of physical activity and arterial stiffness in patients with psoriasis.

In this study, over 50% of people with psoriasis failed to meet the recommended guidelines for exercise as provided by the American Heart Association. Psoriasis severity impacted on exercise behaviour and the DLQI (Dermatology Life Quality Index) identified six key psoriasis-specific barriers to physical activity, including: skin sensitivity, embarrassment, clothing choices, social/leisure activities, engagement in sport and treatment of psoriasis. Controlling blood sugar and lipid levels was found to have a significant impact on arterial stiffness, which is a preclinical indicator of future CVD risk. Importantly, we found that regulation of these biochemical parameters could be modulated by physical activity, thus providing a means to diminish the CVD risk of patients with psoriasis. Given the CVD risk in patients with psoriasis, these findings strengthen the need for intervention.

In addition, through arterial function assessment, we identified that measurement of the diastolic reflection area had utility as a bed-side measure of exercise profile which could provide a means to measure adherence to exercise in the psoriasis population.

2010

Autophagy: a novel therapeutic target for psoriasis.
Professor Nick J Reynolds - Newcastle University

A number of effective psoriasis therapies are strong inducers of autophagy, which is a process of ‘self-eating’ where a cell will degrade or recycle damaged components. In contrast, drugs that make psoriasis worse block autophagy. This suggests that autophagy activation may play a role in the clearance of psoriatic plaques, which was investigated in this project.

Damage to a cell component called mitochondria is known to trigger autophagy. The topical treatment Dithranol can cause mitochondrial damage and cell death, but it wasn’t known if autophagy contributed to the clearance of psoriatic plaques by Dithranol treatment.

The study found that Dithranol activates autophagy in skin cells and that the damaged mitochondria are degraded by autophagy. The results also suggested that autophagy is needed to cause cell death in response to Dithranol treatment. This project also further clarified the signalling pathway that allows Dithranol to cause skin cell death. These findings not only support the hypothesis that autophagy is potential therapeutic target for psoriasis, but the further understanding of the mechanism behind Dithranol could lead to the development of new avenues for potential treatments. 

Cochrane Review update:  Topical Treatments for Chronic Plaque Psoriasis
Dr Anne Mason - University of York

This review describes average benefits of different topical treatments (i.e. treatments applied to the skin), while recognising that individual patients will vary in their experiences of each treatment.

The evidence was based on 175 studies that included 34,808 people. Studies were typically about 7 weeks long, but  ranged from 1 to 52 weeks. Vitamin D products were found to work better than placebo (the base cream or ointment). Potent (strong, e.g. betamethasone dipropionate) and very potent (very strong, e.g. clobetasol propionate) topical corticosteroids were also effective.

Some studies compared vitamin D products directly with potent or very potent corticosteroids. These products had similar effects when applied to the body, but corticosteroids worked better than vitamin D for scalp psoriasis. Treatment that combined vitamin D with a corticosteroid was more effective than vitamin D alone and more effective than the topical corticosteroid alone. Vitamin D products generally performed better than coal tar, but studies found conflicting results when comparing vitamin D with dithranol.

Whether applied to the body or to the scalp, potent corticosteroids were less likely than vitamin D to cause ‘local adverse events’, such as skin irritation or burning, and people were therefore more likely to stop using vitamin D products. When studies examined whether topical treatments had effects within the body (‘systemic adverse events’), we found no difference between placebo and any other treatment. However, this may be because many trials did not properly assess systemic adverse events rather than because there really was no difference.

More long-term studies would help doctors and people with psoriasis decide on the best way to treat this chronic condition.

A multi-centre, prospective, cohort study to establish clinically relevant pharmaco-genetic markers of systemic treatment outcomes in patients with severe Psoriasis.
Dr Catherine Smith - St. John's Institute of Dermatology, London

This study has led to the development of one of the largest psoriasis bio-resources of DNA, RNA (the molecule produced from DNA) and blood serum in the UK. Over 2,000 people with psoriasis were recruited, all of whom are also taking part in the BADBIR study. This means that the collection of biological samples have corresponding clinical data available from BADBIR, allowing future studies to compare biological differences with clinical outcomes.

In addition, the development of this bio-resource proved to be fundamental to the successful bid to the MRC to build the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) Consortium. PSORT will provide ongoing funding to the bio-resource, as well as providing £7 million of investment to bring personalised medicine to people with psoriasis.

2008

Signal transduction of mechanical stress in normal and psoriatic skin.
Dr Julia Reichelt - Newcastle University

This study found that psoriatic skin reacts differently to non-psoriatic skin in response to mechanical stress (stretching). A number of different signalling proteins were investigated and it was found that proteins that were activated in non-psoriatic skin following stretching were not activated, or only weakly activated, in psoriatic skin.

In particular, p38 MAP kinase signalling which, though found to be activated in psoriatic skin, was significantly weaker than the activation seen in non-psoriatic skin. This activation was so weak that proteins which are normally activated by p38 were not activated upon stretching of psoriatic skin. One of these proteins, MSK1 (mitogen and stress-activated kinase 1) is known to stimulate the production of anti-inflammatory signalling proteins called cytokines and can therefore act as a negative regulator of inflammation. This data suggests that the regulation of MSK1 may play a role in psoriasis and MSK1 may be a new therapeutic target.

2007

PhD Studentship – The role of genes predisposing to epithelial inflammation in the pathogenesis of psoriasis.
Maria Quaranta, supervised by Dr Francesca Capon, Professor Richard Trembath and Professor Jonathan Barker – King’s College London.

It has long been recognised that subtle genetic defects can make some individuals especially vulnerable to inflammatory diseases. Prior to the onset of this study, our group had identified alterations in two particular genes (known as IL12B and IL23R), that had been previously shown to malfunction in inflammatory bowel disease (IBD).  Thus, the aim of this study was to investigate whether psoriasis sufferers also carried defects in other IBD genes.

We investigated a total of 29 IBD genes, which were examined in more than 1,200 psoriatic patients. This systematic analysis identified alterations in a third CD gene, known as CDKAL1. Of note, CDKAL1 defects had also been found in patients suffering from type II diabetes. This is of great interest, as it might explain why diabetes occurs at a higher frequency among psoriasis sufferers, compared to the rest of the population.

In the second phase of the research, we investigated how CDKAL1 defects might contribute to disease onset and used genetic engineering techniques to switch off the gene, in cells grown in a culture dish. The analysis of these cells revealed significant alterations in the production of molecules that contribute to inflammation, suggesting that this might be the mechanism whereby CDKAL1 contributes to CD, psoriasis and diabetes susceptibility. More broadly, these results indicate that some disease processes can lead to the onset of different clinical conditions. This notion, which is supported by the results obtained by other groups, has important therapeutic implications, as it implies that similar agents could be used for the treatment of inflammatory diseases such as psoriasis and CD.

A study to investigate self management practices and their development in adult patients with mild to moderate psoriasis.
Dr Steven Ersser – University of Bournemouth.

The main treatment for mild to moderate psoriasis is the regular application of topical medication by the individual. At present little is known about how people with psoriasis self-manage and how they may best be supported in this. This study aimed to explore how adults with mild to moderate psoriasis manage their condition and to identify strategies that can support people to help them self-manage effectively.

The study found that people with mild to moderate psoriasis do not always achieve what they perceive to be optimal self-management. They often do not use topical therapy systematically and frequently abandon it if rapid improvements are not seen. Providing individualised education about improving effective adherence techniques was identified by the patients as one of the factors that would be likely to improve self-management.

In conclusion, people with mild to moderate psoriasis continue to find self-management problematic; however, they can identify strategies that could enable them to become more effective in self-managing. There is a need to incorporate these strategies in “self-management plans” in order to support individuals to self-manage as effectively as possible to help improve their skin condition and quality of life.

The Psoriasis Association is the UK's leading national charity and membership organisation for people affected by psoriasis – patients, families, carers and health professionals Read More >

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