Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial

The influence of the commensal and pathogenic gut microbiota on prion disease pathogenesis

“…In contrast, data from a clinical trial show that the daily treatment of clinical CJD patients with doxycycline did not significantly affect disease progression (Haïk et al, 2014). However, it is difficult to determine a direct role for the effect of these antibiotics on the microbiota in these studies as tetracyclines can also inhibit PrP Sc conversion and prevent neurotoxicity in cultured neurons (Tagliavini et al, 2000).…”

Prions: Beyond a Single Protein

“…In vivo, scrapie-infected Syrian hamsters treated with various tetracycline compounds exhibited a delayed onset of symptoms and prolonged survival times (260,261). Recently, a double-blind, randomized, controlled trial of the use of doxycycline in CJD patients was conducted in Italy; however, this study did not reveal any mortality rate benefit in patients receiving doxycycline rather than a placebo (262). Anthracycline, a tetracycline chemotherapy agent that also binds to amyloid fibrils and prevents amyloid fibrillization in vitro, has also been shown to delay symptom onset and lengthen survival in scrapie-infected Syrian hamsters (263).…”

Doxycycline for Creutzfeldt-Jakob disease: a failure, but a step in the right direction

“…4,5 Results of the trial reported in The Lancet Neurology by Stéphane Haïk and colleagues 6 that used oral doxycycline to treat Creutzfeldt-Jakob disease are no exception to previous study outcomes, with the drug showing no survival benefi t. Nonetheless, it is an important study because it showed that multinational collaborations, rapid enrolment, and rigorous study methods can be achieved for treatment of a rare, rapidly progressive dementia.…”

“…A second major issue with the trial by Haïk and colleagues 6 was the inclusion of patients with very advanced disease. Essentially no exclusion requirements were stipulated for disease severity in the French cohort, and the Italian investigators used time from symptom onset for exclusion as a surrogate for disease severity.…”

“…First, little is known about what patients actually learn when showing improvement in motor performance after stroke. Longitudinal studies with intensive, repeated threedimensional kinematics 6,7 have shown that patients learn to adapt to, or compensate for, their motor defi cits by using their trunk and aff ected arm muscles diff erently. However, the synergy-dependent intra-limb couplings (ie, functionally related, stereotyped patterns of muscle Eff ects of robotic therapy of the arm after stroke…”