Optimising Thiopurine Therapy in Crohn's Disease
Thiopurines are used extensively to treat patients with Crohn's Disease, however they are not effective in up to half of patients and one fifth have to discontinue therapy due to adverse reactions. The project will identify biomarkers that predict intolerance prior to the start of treatment.
Thiopurine therapy is a common treatment for Crohn's Disease, however it is not effective for up to one half of patients and one fifth of those treated have to discontinue therapy due to negative side-effects. If this study succeeds it will identify genetic markers that predict an intolerance to the drugs prior to the start of treatment. This will then translate into a great improvement in treatment outcome in patients
The study will provide a real insight into the tolerance of thiopurines. Having this information available at the onset of treatment will really help patients, avoiding unnecessary delays in finding the most appropriate drug to treat and manage their symptoms. Not only will it be invaluable from a clinical perspective, it will also greatly improve the emotional well-being of Crohn's Disease sufferers.
To identify biomarkers that predict hypermethylation (intolerance) of thiorpruine therapy.
Activities» DNA extracted from blood samples of 200 patients displaying a history of a ‘normal’ tolerance to thiopurine drugs.
» This clinical data will be analysed and compared to that extracted from 200 patients displaying an intolerance and negative side-effects.
» From the analysis, relevant genetic markers will be identifed to determine whether or not patients can tolerate thipurine treatment,
Success will be identifying the genetic markers which will translate directly into clinical practice. This will mean that the best form of treatment will be open to patients.
The project will reverse the cases of thiopurine intolerance in patients, thus greatly improving quality of life and ability to manage the disease. The results of the project will be directly incorporated into clinical practice, ensuring patients receive the best possible drug available to them.
We will demonstrate the success by monitoring patients responses to thiopurines and alternative forms of treatment over a period of time.
We anticipate very few risks as the research laboratory and methods used all have a proven track record in pharmacogenetuc research. One issue could be insubstantial patient samples but we have a large pool of patients outside the hospital Trust (GSTFT) attending private clinics run by the project’s researchers. We have been granted ethical approval by the Outer South East London Research and Ethics Committee (REC reference: 06/Q707/84).
Donors to this project will receive a full report on the outcome of the study at its completion. We will also encourage them to contact us at any stage during the project if they want an interim report.
Budget - Project Cost: £24,912Loading graph....
Amount Heading Description £17,312 Salary 33% of the salary for leading research fellow Dr Paul Blaker £7,600 Consumables e.g. DNA blood mini-kit; QIAamp; Illumina Exome Chip
The project will take place at Guy’s & St. Thomas’ Hospitals NHS Foundation Trust (GSTFT) in London, one of the centres of clinical excellence in the UK. The analysis will take place at the Purine Research Laboratory which has a proven track record in pharamacogentic research.
People with Crohn’s Disease, their families, carers and friends. Medical practitioners & researchers working in the field of IBD.
forCrohns is dedicated to raising funds to go directly to research into the disease. We are a small charity that can fund these smaller, but invaluable, projects.
Read more about the Charity running this project.
Dr Paul Andrew Blaker, BSc MBBS(B) MRCP
Clinical Research Fellow Gastroenterology. Dr Blaker will ensure that the project is delivered as stated and aherad of time.