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Microsoft word - websiteupdate treatment_amm

Professor RSG Knight, NCJDRSU
updated August 2012
Creutzfeldt-Jakob disease and other human prion diseases are invariably progressive and fatal; there is currently no proven treatment for the underlying disease process. The identification of possible treatments can be based on theoretical considerations or on chance observations. In relation to the former, one problem is that the precise disease mechanisms in Prion Disease are not fully understood. Any possible therapy needs to be assessed and there are three broad assessment methods: ‘in vitro’/cell-based assessments, ‘in vivo’ animal experimentation and human clinical trials. The ‘in vitro’ (‘test-tube’) or cell-based methods can be very useful but do not necessarily give reliable information on whether treatments will work in animals or humans with disease. Animal experiments also may not translate directly to humans. Human clinical trials can be difficult to design and run properly. Treatment for human disease can take three main forms: preventative, symptomatic and disease-modifying. Prevention is a reasonable consideration for only those individuals known to be at particular risk of developing disease in the future (for example because of a genetic risk). Symptomatic treatment is treatment designed to help distressing symptoms (for example, anxiety, pain, sleep disturbance) but not to have any effect on the disease process itself. Disease-modifying treatment might slow disease progression, halt it or even reverse it. Unfortunately, Prion Diseases are often not easy to diagnose in the early stages and individuals are often already seriously neurologically impaired at the time when any treatment could be considered. This may well reduce the chance of any therapeutic success and, even if it were to stop disease progression, it would leave the patient in a seriously disabled state. The development of better, earlier diagnostic tests would be helpful in this respect, but, at present, clinicians must work with the available methods of diagnosis. There are a number of potential treatments that have either been considered, are under current consideration or are in development. 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 human Prion Disease. Some comments are made below concerning: Quinacrine, Pentosan Polysulphate,Flupirtine and Doxycycline. a) In the UK, an MRC-funded trial (PRION-1) studied the possible effects of Quinacrine. It stopped recruiting patients at the end of June 2006 and the overall conclusion was that Quinacrine had no significant beneficial effect. Collinge J. et al. Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial. Lancet Neurology 2009;8(4):334-44. b) The MRC funded an independent review of UK individuals who were treated with Pentosan Polysulphate (via the intracerebroventricular route) which has been published. There is some evidence that this treatment can prolong survival in variant CJD (vCJD) but it does not halt progression and there is no good evidence for prolongation of survival in other forms of prion disease. Bone I. et al. Intraventricular pentosan polysulphate in human prion diseases: an observational study in the UK. European Journal of Neurology 2008;15(5): 458-64. c) A German study of Flupirtine was published in a scientific journal in 2004 that reported some beneficial effects on cognitive function in patients with CJD but there is no evidence for increased survival with the treatment.  Otto M. et al. Efficacy of flupirtine on cognitive function in patients with CJD: A double-blind study. Neurology 2004;62(5):714-8. d) More recently, research has centred on Doxycycline as a possible treatment with human trials currently being undertaken or considered in France, Germany and Italy. De Luigi A. et al. The efficacy of tetracyclines in peripheral and intracerebral prion infection. PLoS One 2008;3(3):e1888. MRC PRION UNIT/ NATIONAL PRION CLINIC
As indicated above, the MRC funded a formal treatment trial of CJD. The trial commenced in 2004, stopped recruiting in 2006 and the results were published in 2009. The MRC Prion Unit & the National Prion Clinic in London have an active interest in developing and assessing potential treatments; they intend to organise other human clinical trials in the future. THERAPRION
Theraprion is a EUROCJD associated group that meets to discuss and establish collaboration and uniform data collection in any treatment trials conducted in member countries.


MEDICEAN (GB) (Chesnut 1997) CONCILIATORY (GB) (Grey mare 2007) CONDOLEEZZA (USA) (Grey 2000) 5Sx5S Natalma, 5Sx4D Chambord, 4Sx5D Northern Dancer, 5Sx5D Red God CONCILIATORY (GB), won 3 races (7f. - 8f.) at 3 and 4 years, 2011 and £25,696 and placed once; also placed once in Germany at 4 years, 1st Dam CONDOLEEZZA (USA), won 1 race at 3 years and £7,983 and placed 5 times


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