Little Headway Made in Treatment of Prion Diseases

UK researchers indicate that minimal progress has been made in treatment of prion diseases, such as sporadic Creutzfeld-Jakob disease (sCJD) or the human variant of bovine spongiform encephalopathy (vCJD), during the last 30 years. Their literature review, published in the April 8 issue of Neurology, identified only 1 randomized, placebo-controlled trial of therapy since 1971. The investigators describe many of the examined studies as "flawed" or "poorly reported."

In total, the authors found 33 studies (including case reports) that evaluated a total of 14 interventions (N = 149); 10 of the reports included fewer than 4 patients. Most of the studies evaluated patients with sporadic or unspecified CJD. Examined therapies included analgesic, anticoagulant, anticonvulsant, antidepressant, and antimicrobial drugs.

Therapies studied in the greatest (relative) detail:

Amantadine: The authors identified 2 "questionable" comparative studies (n = 17) and 6 case reports (n = 7), most of which were published during the 1970s. Transient, symptomatic benefits were described for some patients in 1 of the comparative studies and in 3 of the case reports.

Pentosan polysulfate: Disease progression may have been slowed by the anticoagulant in some patients, according to 3 published cases of vCJD and cursory descriptions of another 23 patients.

Quinacrine: In 1 comparative study (N = 32), there were no obvious differences in clinical status or survival between treated patients and "matched concurrent controls." Case studies (N = 50) inconsistently reported symptomatic benefit, and drug-related toxicity (ie, liver dysfunction) was described in 10 studies.

Flupirtine: In the "only reliable reported randomized trial," the analgesic may have slowed cognitive decline, as measured by the cognitive portion of the ADAS-cog. Enrolled patients either had sCJD (n = 26) or genetically determined CJD (n = 2).

Given the rarity of prion diseases (quoted incidence of sCJD = 1 in a million), adequately powered trials will require national and, probably more likely, international collaboration, as the authors indicate. Also logical choices for tested therapies will necessitate a better understanding of how prion diseases are initiated and a more universal consensus of their cause (for an examination of the contentious, opposing views on the prion theory, click here).