Effect of oral administration of pentosan
polysulfate for patients with Creutzfeldt-Jakob disease (CJD) and new design for low
molecular-weight of pentosan polysulfate
Susumu Shirabe\ Katsuya Satoh\ Katsumi Eguchi\ Masami Niwa^, No- riyuki Nishida^, Atsushi Yamauchi"^, Yasufumi Kataoka"^ and Shigeru Katamine^
^The First Department of Internal Medicine, Graduate School of Biomedi- cal Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501 Japan ^The Department of Pharmacology, Graduate School of Biomedi- cal Sciences, Nagasaki University ^The Department of Molecular Micro- biology and Immunology, Graduate School of Biomedical Science, Na- gasaki University ^The Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmacological Sciences, Fukuoka University
<e-mail> [email protected]
Abstract
Although numbers of promising agents to control abnormal prion protein in vitro or in vivo, none of the sufficiently effective and safe agent has been discovered for patients with Creutzfeldt-Jakob disease (CJD). Qui- nacrine and pentosan polysulfate (PPS) have been reported as possible useful agents for treatment of CJD. We administrated PPS oral treatment for eight patients with CJD, then evaluated clinical effects of oral PPS.
Oral PPS were not effective in seven cases except "response to person"
and "frequency of myoclonus" in some patients. One patient was evalu- ated to be effective in "30m walking time" and in improvement of "pres- ervation of words". In this case, these effects were transient.
So, more sufficient delivery system of PPS into brain is needed. Also, intraventricular administration of PPS therapies in animal model and hu- man have been reported. But, it would be difficult to perform these op- erations for all CJD patients, because patients need to have surgical pro- cedures. So we designed to produce the low molecular-weight of pentosan polysulfate (LMW-PPS), because we assumed that LMW-PPS could be pass through blood-brain-barrier (BBB). We collected some
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