Findings of MRC monitoring study of Pentosan Polysulphate treatment in CJD patients
12 July 2006
A Medical Research Council monitoring study of a small number of UK patients has found that a compound called Pentosan Polysulphate (PPS) does not stop the progression of vCJD and other prion diseases but the report recommends more research. The study provides qualified reassurance on some of the safety concerns that have been raised previously. The observational study of seven patients was carried out by Professor Ian Bone from Glasgow, Intraventricular Pentosan Polysulphate in Human Prion Diseases: A study of Experience in the United Kingdom, is a summary of the responses that people with prion diseases have shown to PPS.
The chemical nature of PPS means that it is unable to enter the brain if administered orally or intravenously. For the purposes of this treatment, therefore, it has been administered directly into the ventricles of each patient's brain - a route known as intraventricular delivery. Fluid circulating around the brain from the ventricles potentially provides a route to spread PPS around the brain tissue.
Professor Bone carried out the study based on analysis of seven patients' treatment and he stresses that the findings should not be taken as conclusive, because the report was based on a very small number of patients, treated in different ways, and because like-with-like comparisons with untreated patients were not possible. However any severe side-effects or clear benefit of PPS treatment in halting progression could have been revealed by this study. The findings are being made available now, to inform the debate over this treatment.
The MRC's New Therapies Scrutiny Group endorsed the recommendations of Professor Bone's report:
Further experimental work in animals will provide the most immediate source of evidence of whether or not PPS is likely to extend survival. We need better information on the extent to which PPS penetrates and spreads through the infected brain. The Medical Research Council will take this forward.
Further clinical research could be undertaken. Ideally, a formal prospective longitudinal standardised follow-up study would be required but this must be dependent on the results of the experimental animal work being encouraging. In the meantime, newly diagnosed patients should be informed verbally and in writing about current knowledge of PPS, including the risks associated with intraventricular catheterisation, when treatment options are discussed. The Medical Research Council will take forward this recommendation with the Department of Health.
Informed people opting for intraventricular PPS should undergo the procedure to fit the catheter and pump at a neurosurgical centre with appropriate experience of such surgery. However, dose initiation and escalation could be managed locally. People treated in this manner should be followed up through an approved protocol of clinical assessments and investigations.
Current patients on PPS should continue to be monitored as part of a supportive, structured review, and should be given up to date information and advice.
Professor Bone said: "Pentosan Polysulphate itself does not seem to carry a high probability of side effects from prolonged usage. However, the surgical complications of intraventricular catheter and pump placement were significant. The drug does not appear to halt the progression of the disease. Loss of brain function continues after treatment has started and, where measured by imaging, loss of brain tissue also continued. This is the first time that this mode of drug delivery has been carried out over such a prolonged period of time. The study shows that intraventricular delivery might provide a long-term alternative route for other future therapies that cannot enter the nervous system by oral or intravenous routes in situations where the surgical risks are justified."
He went on: "The patients treated with PPS appear to have survived for unusually long periods. However, we cannot conclude with certainty that the treatment has a beneficial effect, because it was impossible to make direct comparison with similar but untreated patients. Moreover, with such small numbers the results might be a matter of chance. The report recommends specific laboratory experiments to address the uncertainties."
Professor Ian Bone said "I am very grateful to the families and patients who participated in the study, and I hope that my report will help people who have to take difficult decisions about treatment in future. A report like this cannot always offer definite answers, and we urgently need further rigorous research to give scientists, doctors, patients and their families more information on which to base future treatment decisions."
The co-chair of the committee, Professor Sir Michael Rawlins welcomed the study: "Professor Bones observations have helped cast light on a little known and difficult-to-research area. He has shown that Pentosan Polysulphate itself does not appear toxic at the modest doses given and leaves open the intriguing possibility that it may have some effect on the duration of survival. Sadly it seems that a loss of brain function continues in patients being treated with PPS. Professor Bone has also confirmed what we knew at the outset that the surgical procedure needed to administer PPS carries a degree of risk, though is generally considered to be acceptable given the advanced stage of the disease in these patients. The recommendation that surgery be carried out in an experienced centre, and to an approved protocol, should help reduce complications associated with the surgery."
Lester Firkins, the other co-chair, added: "This is a very important report which will inform current and future patients and their families and also our collective knowledge of this tragic disease. I am very pleased that the MRC New Therapies Scrutiny Group agreed to advise MRC to carry out further research as a matter of urgency to fill in the gaps in the knowledge on PPS. Additionally, it should now be possible to help new patients and their families with better information on the risks of PPS by the publication of a balanced information leaflet. We are all indebted to the current patients and their families for participating in this study and of course they must continue to benefit from appropriate monitoring and support."
If you would like to arrange an interview please contact the MRC press office:
Phone number: 020 7637 6011
Email: press.office@headoffice.mrc.ac.uk
Notes for editors:
MRC New Therapies Scrutiny Group for Prion Disease
The MRC New Therapies Scrutiny Group for Prion Disease (NTSG) was established in 2005 at the request of the Chief Medical Officer (CMO), to provide an independent source of advice on research into the development of potential therapeutics or preventative agents for prion disease. NTSG will build upon the previous work of the Department of Health CJD Therapy Advisory Group (TAG).
NTSG reports to the Medical Research Council (and other bodies when appropriate). The Group will advise MRC on the development of new therapeutic agents that could possibly be brought to bear upon this disease and will also maintain an overview of other relevant research.
The Medical Research Council
The Medical Research Council (MRC) is funded by the UK tax-payer. It aims to improve human health. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and universities. The MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK.
