Potential treatments for Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob disease and other human prion diseases are invariably fatal and there is currently no proven treatment for the underlying process. There are however a number of potential treatments in development or under consideration. It must be stressed that, to date, no treatment has been shown conclusively to slow or halt the disease process in humans with any form of CJD. There has been media coverage of two potential treatments in particular: Quinacrine and Pentosan Polysulphate.


Quinacrine


Dr Prusiner's group from San Francisco published an article in Proceedings of the National Academy of Sciences on 14/08/01 entitled 'Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease'. This article provided evidence of inhibition of the formation of the disease associated form of prion protein in scrapie infected neuroblastoma cells by a number of compounds, with quinacrine and chlorpromazine exhibiting the greatest potency.


The first paragraph of the article concludes "Beacause quinacrine and chlorpromazine have been used in humans for many years as anti-malarial and anti-psychotic drugs respectively, and are known to pass the blood brain barrier, we suggest that they are immediate candidates for the treatment of Creutzfeldt-Jakob disease and other prion diseases". More recently, Barret et al published a paper concerning laboratory experimental work on quinacrine, suggesting that its use as a treatment for CJD was questionable.


There was a report in The Mail on Sunday, on Sunday 12 August, entitled "Briton 'cured' in CJD drug trial". The article described a 20-year-old female with variant CJD who was treated in a pioneer drug trial in San Francisco and in whom the family reported clear neurological improvement.


Any finding that might lead to an effective treatment of CJD is to be welcomed. However, laboratory findings are simply indications of possible therapeutic value and the real test is whether a compound is actually effective (and safe) in human beings with disease.

Further work is essential in order to establish whether these drugs can provide an effective treatment and proper assessment needs to be carried out in the context of a well designed clinical trial. A preliminary trial was undertaken by the National Prion Clinic/MRC in London and a more extensive MRC trial is due to start in 2004. Further information on this will be circulated to all neurologists in the near future.


Relatives of patients currently suffering from CJD (including vCJD) may wish to obtain further information on this subject, with a view to consideration of initiating treatment with these compounds. Information on the current and proposed clinical trials can be obtained from the National Prion Clinic. Quinacrine and chlorpromazine are available in the UK, but neither are licensed for use in the treatment of human prion diseases and would need to be prescribed in the context of a trial, or on a named patient basis.

A suggested treatment regimen for quinacrine is 200mg 6 hourly for 5 doses followed by 100mg tds. Quinacrine (Mepacrine hydrochloride) is available from BCM Special in Nottingham, telephone number 0800 952 1010. The role and dosage regimen of chlorpromazine is uncertain and patients who have been treated to date have often received quinacrine alone.


Other treatments include: Pentosan Polysulphate - Risks of Intraventricular PPS - Benefits of Intraventricular PPS


Dr RSG Knight, NCJDSU