Refining the clinical use of pentosan polysulphate for TSEs: animal models of intravenous infection and intervention

Over 180 people have developed the fatal disease vCJD from eating meat and meat products from cattle with bovine spongiform encephalopathy. There is now evidence that vCJD can be spread from person to person by blood transfusion. There is no test and there is a long silent phase when people are infected but no one knows. A few young patients have been given a drug, pentosan polysulphate, directly into their brains and this seems to slow the disease down. This method was used because it was not thought the drug could get into the brain if it was injected intravenously but we now have some evidence from scrapie infected mice, which is a similar disease, that some may get in by this route as we have been able to extend their lives. We propose to investigate how we can get more of the drug into animals without needing to resort to delivering it straight into the brain and to do this safely.

BSE has passed from cattle into the human population presenting as vCJD. There is now evidence of human to human transmission by blood transfusion. There is no licenced treatment for any of the TSEs which are invariably fatal. Pentosan polysulphate has efficacy in animal TSE models and has been given to some patients intraventricularly as it is not thought to cross the blood brain barrier after parenteral injection. We have evidence that intravenous PPS can increase survival time in mice with symptoms of scrapie and intend to determine the relationship between disease, the blood brain barrier and PPS ingress into the central nervous system.