Medicines committee felt unable to recommend use of pentosan polyphosphate in vCJD

Pentosan polysulphate, the drug used for the last eight months to treat a UK teenager with variant Creutzfeldt-Jakob disease (vCJD), was reviewed by the Committee on the Safety of Medicines last year.

In its review (October 2002), the Committee felt unable to recommend its use in vCJD because of the absence of in vitro or in vivo data relevant to vCJD and the lack of information on the basic pharmacology of the drug, including its mode of action in this indication.

In particular, the committee considered that it could not recommend the intraventricular infusion of pentosan polyphosphate to be used as a treatment in humans for established vCJD disease. It recommended that the drug should be evaluated in models resembling human disease as closely as possible, including mouse BSE (bovine spongiform encephalopathy) and sheep BSE models.

The CJD Therapy Advisory Group agreed with this opinion but “acknowledged that healthcare professionals may be more risk averse than patients or their families when considering potential treatments for incurable diseases such as CJD.”

The teenager who has been treated with the drug is 19 year old Jonathan Simms from Belfast, Northern Ireland. His treatment started after the High Court ruled last December that the potential benefits outweighed the risks (BMJ 2003;326:8). Last week doctors reported a slight improvement in the patient's condition (4 October, p 765).

Pentosan polysulphate (poly-b-xylose-2,3-disulphonate) is a large polysulphonated polyglycoside. The drug is relatively inexpensive—made from beechwood—and has been used since the 1960s as an anticoagulant, in a similar way to heparin, also a polysulphonated polyglycoside. It is currently used in North America for treating interstitial cystitis but is not licensed in the United Kingdom.

It has not been used previously to treat human vCJD, although animal studies have shown that injecting the drug into the brains of animals infected with scrapie, a disease closely related to CJD, slowed the accumulation of prions—the infectious particles implicated in transmission and progression of CJD.

It has been suggested that pentosan binds to heparan binding sites on infectious prion proteins, potentially inhibiting further prion production. The drug has to be given directly into the brain because it is unable to cross the blood brain barrier.

Use of pentosan polysulphate in the treatment or prevention of vCJD can be found at www.doh.gov.uk/cjd/pentosan.htm