2005 Grants

In October Trustees of the Association agreed 3 new research grants shortlisted by the Research Committee. The total awarded was £133,739
These are short summaries of each of the projects.

A national database for psoriasis(DatPso UK) – examination of the interplay between genotype and phenotype
Professor Jonathan Barker, St Johns Institute of Dermatology, London
Over the past 12 years considerable progress (in part sponsored by the Psoriasis Association) has been made in understanding the genetic basis of psoriasis. The region of the human genome harbouring the most important gene has been well characterised and there is now a great effort worldwide to precisely pinpoint what this gene is and what are the other genes that contribute to psoriasis.
A major requirement to enable these studies is knowledge of precise clinical data and DNA on large numbers of patients (estimated to be between 2000 and 3000) together in a single database. This information needs to be stored on secure, anonymised, robust computer databases with processing power capable of handling very large amounts of data. This project describes how a database could be created from information recorded in three large clinical centres in the UK. The database will provide the framework for advancing research aimed at understanding the causes of psoriasis. It could, for example, be used to identify why psoriasis is so variable between patients and why some patients respond to certain treatments and others do not.
The database will require the fully informed consent of all patients whose information is used, with all appropriate safeguards as set out in the Data Protection Act.

Role of epidermal apoptosis in the clearance of psoriatic plaques
Professor Nicholas Reynolds, Dermatological Sciences, University of Newcastle upon Tyne
Dithranol is an effective topical treatment for psoriasis inducing clearance of psoriatic plaques resulting in a period of remission. Dithranol is relatively specific for psoriasis and is not used in the treatment of other inflammatory disorders. We have therefore been studying the mechanism of action of dithranol with a view to gaining insight into how it works. Our recent studies indicate that dithranol induces programmed cell death of keratinocytes. Keratinocytes are dividing more quickly in psoriatic skin, their time of transit from the basal layer to the stratum cornea is reduced and their programme of differentiation is incomplete. Therefore, programmed cell death by dithranol may represent an important mechanism of action that could account for the clearance of psoriasis.
In order to investigate whether this is a general mechanism, we now propose to study whether a wide variety of anti- psoraitic drugs including topical, sytemic agents and TNF alpha therapy induces programmed cell death of keratinocytes within psoriatic plaques. Mitochondria, the powerhouse of the cell are known to play a key role in programmed cell death and we will investigate whether other anti psoriatic drugs target mitochondria like dithranol. The studies will provide insight into the mechanisms involved in the clearance of psoriasis and will therefore increase our understanding about disease mechanisms. In the long term we aim to develop more specific assays to allow screening for new drugs with the aim of developing novel therapies with improved effectiveness and better side effect profiles.

What is the optimum method for measuring minimal erythema dose (MED) for narrow band phototherapy?
Dr Harry Moseley, Photobiology Unit, University of Dundee
The minimal erythemal dose (MED) is used in many dermatology departments to help determine the optimum starting dose for phototherapy. In this way each patient is tested to derive a safe starting dose. The standard method involves setting the patient at a fixed distance from a bank of lamps and exposing the patient’s back to a series of doses. The main problem in the measurement of MED is the practical difficulty in carrying out the procedure. Commercial devices are now available that simplify the procedure and substantially reduce the time required to carry out the test but these have not been validated against the standard test. The purpose of this study is to carry out a comparison betwwen the standard method and two systems that are commercially available and a third system that has only recently been developed.

A helpful glossary of terms and a cross section of skin!

Genotype - This is the "internally coded, inheritable information" carried by all living organisms. This stored information is used as a "blueprint" or set of instructions for building and maintaining a living creature.

Phenotype - This is the "outward, physical manifestation" of the organism. These are the physical parts, the sum of the atoms, molecules, macromolecules, cells, structures, metabolism, energy utilization, tissues, organs, reflexes and behaviours; anything that is part of the observable structure, function or behaviour of a living organism.

Apoptosis – programmed cell death

Keratinocyte – types of cells that make up over 95% of the epidermis ( the outer layer of the skin)

Mitochondria - provide the energy a cell needs to move, divide and produce secretory products – the power centre of the cell.

Assay – the determination of the amount of a particular constituent of a mixture or of the biological or pharmacological potency of a drug.

Novel – new

Erythema – redness of the skin