“Translating experimental stroke therapy to patients: determination of optimal dosing and biological efficacy of IL-1RA”.
Overview of the MRC Experimental Medicine programme Grant
Stroke is one of the leading causes of mortality and morbidity in the Western World. Despite intensive research, only thrombolysis (rt-PA) has been approved for treatment of stroke but it is only indicated in selected cases. There is considerable evidence showing that inflammation plays an important role in brain injury secondary to stroke. Interleukin-1 (IL-1) is one of the key proteins of inflammation.
IL-1 can be blocked by a naturally-occurring protein (IL-1RA) and this has been shown to be neuroprotective in early studies which show that IL-1RA may be an effective treatment of brain inflammation following stroke.
Kineret® (a manufactured form of IL-1RA) has been used as a second line treatment for rheumatoid arthritis for several years and has a very good safety record. It has also been given to patients in other trials, including stroke. Given into a vein (IV) it is known to cross over to the brain and reach concentrations that have been previously found to protective brain tissue.
Our programme of research is divided into three parts
- Study 1 is aimed at finding the best IV dose regime of Kineret®, which will achieve sufficient brain concentrations within thirty minutes of infusion. – See study 1 overview
- Study 2 will be a comparison between Kineret and placebo (dummy drug) (known as a double-blinded randomised placebo-controlled study). We will give Kineret® (using the dose identified by the first study) or a placebo to subarachnoid haemorrhage patients. These patients will also have a drain inserted for clinical reasons. Analysis of fluid from the drain will enable us to study the concentrations of various molecules involved in inflammation and see the effect that Kineret® is having on them. This will provide proof of the actions of IL-1RA within the brain.
The evidence we obtain from the studies will inform the design of future clinical trials including those assessing the effectiveness of Kineret® in patients with Stroke and other forms of brain injury.
The grant is collaboration between Salford Royal Foundation Hospital Trust and Cambridge University Hospitals Trust and Universities of Manchester and Cambridge.
See below for personal profile of study staff:
Prof Nancy Rothwell (Chief Investigator) Deputy President and Deputy Vice Chancellor,
University of Manchester
http://www.ls.manchester.ac.uk/research/themes/neurosciences/neuralinjuryandrepair/
Dr Pippa Tyrrell, Senior Lecturer and Hon Stroke Physician, University of Manchester Brain Injury
Research Group http://www.medicine.manchester.ac.uk/staff/pippatyrrell
Mr Andrew King, Clinical Director of Neurosurgery, Salford Royal Foundation Hospital Trust
http://www.srht.nhs.uk/
Dr Stephen Hopkins, Principal Scientist, University of Manchester Brain Injury Research Group
http://www.medicine.manchester.ac.uk/staff/77684
Andy Vail, Statistician and Senior Lecturer, Salford Royal Foundation Hospital Trust
http://www.medicine.manchester.ac.uk/staff/77570
Mr Peter Hutchinson, Senior Lecturer and Hon Consultant Neurosurgeon, Cambridge University
Hospital Trust http://www.neuroscience.cam.ac.uk/directory/profile.php?pjah2
Mr Peter Kirkpatrick, Senior Academy Fellow Honorary Consultant Neurosurgeon, Cambridge
Cambridge University Hospital Trust
http://www.neuroscience.cam.ac.uk/directory/profile.php?kirkpatrick