Department of Health Skip to content

Please note that this website has a UK government access keys system.

Page menu

Use of Pentosan Polysulphate in the treatment of, or prevention of, vCJD

  • Last modified date:
    21 February 2008

Pentosan Polysulphate has been proposed as a potential prophylactic or therapeutic agent for CJD. In October 2003, the UK Health Departments asked the Committee on Safety of Medicines (CSM) and the CJD Therapy Advisory Group to review their current advice in light of clinical information on the single patient who had been receiving cerebroventricular Pentosan Polysulphate since January 2003, and on new unpublished research data.

Advice from the CJD Therapy Advisory Group

The CJD Therapy Advisory Group considered that:

  1. There are insufficient clinical data available to support the claim that Pentosan Polysulphate is effective during clinical disease;
  2. There are insufficient safety data upon which to base a rational treatment regimen in humans;
  3. Further experimental study in animal models is warranted, including dose-finding studies in appropriate strains of human prion disease.
  4. Nevertheless at the dosage used (11µg/kg per day) in the one human patient treated to date, there have been no definite harmful effects attributable to the drug.
  5. All patients with prion disease should undergo appropriate monitoring during disease progression, in a way that allows collection of data on the natural history of disease and on any treatments that might be given.

Members acknowledged that healthcare professionals may be more risk averse than patients or their families when considering potential treatments for incurable diseases such as CJD.

Advice from the Committee on Safety of Medicines

The Committee on Safety of Medicines (CSM) has considered whether pentosan polysulphate (PPS) has any role in the prophylaxis or treatment of vCJD on a number of occasions since February 1999.

The Committee was unable to recommend its use in these indications because of the limited data then available for supporting a rationale for use in the prophylaxis or treatment of vCJD.

A working group of the CSM reviewed the latest scientific evidence in October 2003 and concluded that:

  1. At present there are very limited data from animal models that may be relevant to vCJD indicating that PPS might be an effective prophylactic agent for this disease. There is no evidence in support of its use as a treatment in late stage disease.
  2. Although there is information on the basic pharmacology of PPS there is limited information relevant to these indications.
  3. There is insufficient information that could form a rational basis for prescribing PPS as a treatment or prophylactic agent for vCJD. In particular there is limited information on the route(s), dose(s), duration, or timing of the PPS administration in relationship to the receipt of or contact with potentially infectious material.
  4. The administration of PPS is associated with an adverse event profile which raises some concerns, particularly with regard to the potential for bleeding events and hypersensitivity reactions, neither of which have been adequately documented or quantified.
  5. In light of the limited information on PPS treatment of clinically established vCJD it is impossible to assess the risk/benefit relationship of PPS in these indications.
  6. On scientific grounds to support human trials using oral or parenteral prophylaxis or to treat established clinical neurological disease using cerebroventricular PPS, evaluation should be undertaken in models that resemble human disease as closely as possible. These studies in animals should aim to establish:
    a. The appropriate route(s) of administration for prophylaxis and for treatment of vCJD.
    b. Information on the pharmacokinetics in this indication by developing appropriate assays for PPS.
    c. A dose response and optimum dose.
    d. The appropriate duration of treatment.
    e. The timing of administration of treatment in this disease.
    f. A safety profile in animals with an optimum dose that is likely to have an appropriate safety profile in humans.
    g. The PPS WG has concerns over the standardisation of the molecular size and detailed structure of the PPS used for cerebroventricular infusion because efficacy and toxicity (particularly anticoagulant effects) differ with different molecular sizes and structures of other sulphated polyanions such as heparins and dextran sulphate.
    h. In both animal models and humans, objective markers for measurements of the extent of the disease should be established.
  7. The Committee recognizes that a patient with vCJD has received cerebroventricular PPS and further patients are likely to do so. The committee felt that there was, as yet, insufficient information to reach any conclusions about the efficacy of treatment in this single patient. It appeared difficult to distinguish spontaneous variation in the patient's clinical condition from features which might otherwise suggest improvement. In the same way experience in this single patient did not permit secure conclusions about the likely treatment safety. The committee also commented that cerebroventricular infusion of PPS should be of an appropriate quality for administration by this route for treatment in humans of established vCJD or other neurological conditions. There is a need to collect safety and efficacy data on PPS and also to establish robust methods for monitoring the effects of treatment on the disease and these should be achieved in the clinical trial setting.

This summary of the PPS Working Party recommendations was presented orally to the CSM on Thursday 30th October 2003 and the CSM endorsed the Working Party's recommendations.

October 2002 advice

In October 2002, the UK Health Departments asked the Committee on Safety of Medicines (CSM) and the newly-formed CJD Therapy Advisory Group to review the current research, including recent unpublished data, and to advise.

Advice from the CJD Therapy Advisory Group

The CJD Therapy Advisory Group considered that:

  • There is insufficient clinical data available to support the claim that Pentosan Polysulphate may be effective during clinical disease;
  • There is insufficient safety data upon which to base a treatment regime in humans;
  • Nevertheless, further experimental study in animal models is warranted, including dose-finding studies.

Members acknowledged that healthcare professionals may be more risk averse than patients or their families when considering potential treatments for incurable diseases such as CJD.

Advice from the Committee on Safety of Medicines

The Committee on Safety of Medicines (CSM) has considered whether the drug Pentosan Polyphosphate has any role in the prevention of vCJD on a number of occasions. In addition, in October 2002, the Committee considered a potential role for the drug in the treatment of established vCJD.

It first considered these issues in February 1999 when the Committee considered the potential use of Pentosan Polyphosphate for the prophylaxis of vCJD. At that time the Committee was unable to recommend its use in this indication because:

"There is noin vitro or in vivo data relevant to vCJD to indicate that Pentosan Polysulphate might be a clinical effective prophylactic agent in this disease.

There was no information on the basic pharmacology of Pentosan Polysulphate, including its mode of action relevant to this indication.

There is no data that which could form a rational basis for prescribing Pentosan Polysulphate in this indication. In particular, there is insufficient information on the ideal route, dose, duration, or timing of the Pentosan administration in relationship to the receipt of or contact with potentially infectious material.

The administration of Pentosan Polysulphate is associated with an adverse event profile, which raises some concerns, particularly with regard to the potential for bleeding events and hypersensitivity reactions, neither of which have been adequately documented or quantified. These risks could be especially important to certain groups, for example, the elderly, patients pre- or post-surgery, those with bleeding disorders, and those receiving cytotoxic drugs.

The absence of the above information makes it impossible to assess the risk/benefit relationship of Pentosan Polysulphate in this indication."

In March 2001, the CSM re-considered this issue and concluded that there was no new evidence either in vitro or in vivo to support the use of Pentosan as a prophylactic agent.

A working group of the CSM reviewed the latest scientific evidence in October 2002 and concluded that:

  • It did not consider that its previous advice, concerning the use of Pentosan Polysulphate as a prophylactic agent against vCJD needed to be revised.
  • It could not recommend the intraventricular infusion of Pentosan Polyphosphate be used as a treatment in humans for established vCJD disease.

It considered that, before human trials of prophylaxis or the treatment of established disease be considered, the role of Pentosan Polysulphate in the prophylaxis of disease and treatment of established disease should be evaluated.

This evaluation should be undertaken in models that resemble human disease as closely as possible, for example, the mouse BSE and sheep BSE models. Studies in animals should aim to establish:

  • The appropriate route(s) of administration for prophylaxis and for the treatment of established disease.
  • Information on the basic pharmacokinetics by developing appropriate assays for Pentosan Polysulphate.
  • A dose response and optimum dose.
  • The appropriate duration of treatment.
  • The timing of administration of treatment in the disease process.
  • An appropriate safety profile in animals with an optimum dose that is likely to have an appropriate safety profile in humans.
  • In both animal models and humans, objective markers for measurements of the extent of the disease process should be established.

This summary of the Working Party recommendations was presented orally to the CSM on Thursday 31st October and the CSM endorsed the Working Party's recommendations.

Further work

The Department will take into account the advice of these two expert groups in considering priorities for further research.

Information on current research on Pentosan Polysulphate, together with other research on CJD, which is being funded by the Department of Health, can be found at:

Access keys