Treatment with Anti-malaria Agents, Quinacrine and Quinine, for Creutzfeldt - Jakob disease patients

Abstract

Objects To assess effects and safety of treatment with anti-malaria agents as treatment for Creutzfeldt-Jakob disease (CJD). Background There have been no effective treatments for CJD. Several chemicals inhibit an accumulation or a conformational change of prion protein in vitro. Anti-malaria agents such as quinacrine and quinine are known to have anti-prion effects. Materials and Methods The study was approved by the institutional ethics committee, and patients' relatives gave consent for the procedure. Thirty-one caseswere treated with quinacrine including 22 with sporadic CJD, 5 cases with iatrogenic CJD, and 4 cases with familial CJD. Quinacrine 300 mg/day was administered enterally for three months. Six cases with sporadic CJD treated with quinine. Quinine 1.5 g/day was administrated enterally for three months. Motor andcognitive functions were monitored. Results Anti-malaria agents were well tolerated except for abnormal liver function tests, dermatitis or thrombocytopenia. Increased arousal levels and responses to visual and auditory stimulation were seen in 12 patients with quinacrine treatment. Out of 22 sporadic CJD, only one case improved from akinetic mutism. The other 8 patients, who had positive responses as eye contact to verbaland/or visual stimuli before treatment, showed clinical improvement. Out of 5patients treated with quinine, two cases showed improved response to auditoryand visual stimuli. Clinical improvement was transient and lasted for one to two months during treatment. Conclusion This is the first observation of moderate reversibility of cognitive function in a large series of patients with CJD treated with anti-malaria agents. Liver dysfunction is the major complication and sometimes requires discontinuing this medication. It is also suggested that quinacrine/quinine could be the treatment of choice for patients with CJD. However, these agents are notable to prevent the clinical declines or to improve these features. Optimal treatment regimen and further clinical trial will be required.