Pentosan polysulphate prolongs survival in CJD, study indicatesBMJ 2006; 333 doi: https://doi.org/10.1136/bmj.333.7560.166-d (Published 20 July 2006) Cite this as: BMJ 2006;333:166
An experimental treatment for Creutzfeldt-Jakob disease (CJD) may prolong life but does not seem to halt progressive deterioration of the brain, a study of seven British patients who took the drug has found.
Pentosan polysulphate, widely prescribed in pill form around the world for urological conditions, is infused directly into the brain of patients with CJD.
Ian Bone, a Glasgow neurologist, did the study on behalf of the Medical Research Council. Of the seven patients, three had variant CJD (vCJD, contracted from bovine spongiform encephalopathy); two had iatrogenic prion disease from growth hormone; and two had the hereditary form of CJD. All were aged under 35. Three of the seven died before the study's end.
Professor Bone told the BMJ that his findings indicated, but did not prove, that the drug prolongs survival. “The average survival in vCJD is generally believed to be about 13 months. All of these patients lived longer than that from time of diagnosis.”
But he added that the patients continued to experience progressive neurological damage throughout the trial, measured both by brain function and by imaging of brain tissue.
The extended survival of patients in the study has four possible explanations, he said: “One is that our figure for expected survival is wrong because previous patients may simply have been diagnosed late in the course of their disease.”
“A second possibility is that these patients survived longer due to aggressive treatment of comorbid conditions like pneumonia. But the observational data suggest that is not the case. Thirdly, it may be a simple chance finding due to the very small sample. Finally, there might be a real effect from this drug.”
Eight patients have received treatment with pentosan polysulphate in Britain, and “13 or 14” worldwide, said Professor Bone. The drug was originally rejected as a possible CJD treatment by Britain's Committee on Safety of Medicines, but the family of Belfast vCJD patient Jonathan Simms won court permission to try the treatment in 2003 (BMJ 2003;326:8).
Mr Simms, aged 21, is now the world's longest surviving vCJD patient. He continues to receive the treatment, but did not participate in Professor Bone's study.
The Medical Research Council's prion unit is studying another potential treatment for vCJD, the antimalarial drug quinacrine. Recruitment has just finished, and no results are expected for at least a year. The researchers have already warned that “the evidence to date for any possible clinical benefit is very scarce.”
Professor Bone acknowledged that his findings left the question of pentosan polysulphate's use “up in the air.” But he added, “There are some things the families can take away from this. There will now be more research, particularly animal research, because we need to measure the drug's penetration into the brain. Also, the concerns over possible dangerous side effects seem to be groundless. And there is limited evidence of prolongation of life.”
Professor Sir Michael Rawlins, the chairman of the National Institute for Health and Clinical Excellence, welcomed the findings, commenting, “Professor Bone's observations leave open the intriguing possibility that [pentosan polysulphate] may have some effect on the duration of survival.”