• Survival from the time of randomization
  

• Scores on functional scales, neurological exam and functional testing
  

Creutzfeldt-Jakob disease (CJD)is a rapidly progressive, invariably fatal and untreatable neurodegenerative disease with a mean duration of about eight months. Beyond the debilitating cognitive and motor deficits that accompany CJD, the difficulty in treating behavioral and mood disturbances and the rapidity of its course compound its tragedy. Recent results from experiments show that, at physiological concentrations, the anti-malarial drug quinacrine permanently clears abnormal prion proteins from cell culture. The demonstrated efficacy of quinacrine in cell culture, its relative safety and well known side-effects in the clinical setting, and the universal fatality of CJD justify quinacrine as an immediate candidate for the treatment of CJD.

The purpose of this clinical trial is to determine the efficacy of the medication quinacrine on survival in sporadic CJD (sCJD). This will be accomplished by bringing approximately 60 patients with probable or definite sCJD over approximately three years to UCSF for evaluation and initiation of a randomized, double-blinded, placebo-controlled (delayed treatment start) treatment study of quinacrine. Each patient will have a 50:50 chance of being placed on quinacrine or placebo upon study enrollment; however, all patients will be offered quinacrine after two months. Prior to study enrollment, patients will have a comprehensive clinical assessment to confirm the diagnosis of sCJD. Participants will come to UCSF for initial evaluation, potential study enrollment and, if possible, return to UCSF for follow-up at two and twelve months. Patients will receive telephone follow-up (every 2 weeks for the first two months and monthly thereafter) and local blood and testing to monitor for possible medication toxicity.

Inclusion Criteria:

• Diagnosis of probable or definite sCJD: Definite--biopsy confirmed sCJD; Probable--a progressive dementia with either a typical EEG or a typical MRI consistent with sCJD, and at least two of the following clinical features: myoclonus, pyramidal or extrapyramidal signs, visual symptoms, cerebellar signs, akinetic mutism, other focal higher cortical neurologic signs (e.g. neglect, apraxia, aphasia)
• 18 years of age or older
• Able to swallow
• Able to follow simple one-step commands
• Have had a brain MRI within 6 months and an EEG within 3 months ruling out other etiologies such as masses, strokes, or non-convulsive status epilepticus
• Consent to autopsy in the event of their death during or after the study

Exclusion Criteria:

• History of other significant or life-threatening disease, including: cancer; end-stage liver or renal disease; severe heart disease
• History of other disease requiring regular supportive care
• Liver disease
• Active alcoholism
• Bone marrow suppression
• Severe hypotension
• Severe psoriasis
• Poorly controlled diabetes
• Women who are pregnant or breast-feeding
• Men, or women of childbearing age, not practicing reliable contraception
• Serious allergies to quinacrine or other acridines
• Current or recent use of quinacrine (within 6 months)
• < 18 years of age
• Any other contraindication to taking quinacrine
• Genetic form of prion disease is identified prior to study enrollment
• Current use of anti-arrhythmics (at discretion of investigator)
• G6PD (Glucose 6-Phosphate Dehydrogenase) deficiency (at discretion of investigator)