Skip to main content

Or 34,00 After 66% tax deduction

I make a monthly donation I make an IFI donation
Research, science & health

Creutzfeldt-Jakob disease: new perspectives

Published on: 29/01/2011 Reading time: 1 min
image

An international clinical trial in Creutzfeldt-Jakob disease was conducted in France and Italy. Led in France by reasearchers from the Brain and Spinal institute (Jean Philippe Brandel and Stéphane Haïk), this study opens new perspectives for the implementation of controlled-trials in Creutzfeldt-Jakob disease. Results of this study are published in the prestigious journal Lancet Neurology (online publication 8th of January 2014 and issue of February).

Creutzfeldt-Jakob disease (CJD) is one of the most frequent prion diseases in humans. In most instances (more than 85%) the disease is sporadic and occurs spontaneously and randomly. Genetic forms associated with mutations in the gene coding for the prion protein account for 15% of cases. The disease is rarely acquired through medical procedures or exposure to tissue infected with the agent of bovine spongiform encephalopathy. In infectious forms, the incubation period is long and can last for decades in humans. After clinical onset, disease duration is short and death occur in few months. No effective treatments for CJD exist at present. The rarity of the disease (1-2 new case per million of habitants), the distribution and the subacute evolution of the disease limited for a long time the implementation of controlled-clinical trials (where a new therapy is compared to a placebo or an effective molecule used as a reference).

 
In vitro and in vivo experimental results suggested an anti-prion effect of doxycycline. Morever, previous observational studies in Italy and Germany suggested that a daily treatment with 100mg of doxycycline increases survival for treated-patients compared to historical cohorts. Relying on these corroborating and promising results, an international placebo-controlled trial took place in France and Italy. This is the first international trial and the largest controlled-trial performed in this disease.

 
In France, patients were enrolled with rapid administrative procedures to enable local referring centres to become study sites. In two years, this original procedure allowed recruitment of 71 patients in 49 investigator centres whose 27 were opened using accelerated procedures.

 
The first intermediate analysis didn’t show significant effect of the treatment on patient survival and concluded that trial continuation was useless. This was confirmed by the final analysis on the overall patients in France and Italy. Doxycycline concentration measurements performed for the first time in the human brain suggested that a daily administration of a higher dose of doxycycline could be beneficial.

 
Despite these negative results, this study gave major knowledge for the assessment of future treatments in CJD :
- Placebo-controlled trials are feasible in CJD
– These trials are of major interest since open-label trials in CJD suffer from severe selection bias.
– Buidling of multinational trials is required to allow the recruitment of a sufficient number of patients in a such rare and rapidly fatal disease.

 
Thanks to this first international experience and depending on the evolution of scientific datas, the implementation of a future European trial will be discussed.

image
Brain MRI of a patient with the Creutzfeldt-Jakob disease

This study has been led in France by Doctors Jean-Philippe Brandel et Stéphane Haïk (researchers in the team “Prion and Alzheimer’s diseases” at the Brain and Spinal cord Institute (Inserm, Université Pierre et Marie Curie, CNRS) and neurologists of the national centre of reference for CJD (AP-HP, Hôpital de la Salpêtrière) in collaboration with the clinical research unit of the Salpêtrière and with the DRCD of the AP-HP. The Italian part of the study was coordinated by Pr. Fabrizio Tagliavini (Istituto Neurologico Carlo Besta, Milan).

Sources

Stéphane Haïk*, Gabriella Marcon*, Alain Mallet, Mauro Tettamanti, Arlette Welaratne, Giorgio Giaccone, Shohreh Azimi, Vladimiro Pietrini, Jean-Roch Fabreguettes, Daniele Imperiale, Pierre Cesaro, Carlo Buffa, Christophe Aucan, Ugo Lucca, Laurène Peckeu, Silvia Suardi, Christine Tranchant, Inga Zerr, Caroline Houillier, Veronica Redaelli, Hervé Vespignani, Angela Campanella, François Sellal, Anna Krasnianski, Danielle Seilhean, Uta Heinemann, Frédéric Sedel, Mara Canovi, Marco Gobbi, Giuseppe Di Fede, Jean-Louis Laplanche, Maurizio Pocchiari, Mario Salmona, Gianluigi Forloni, Jean-Philippe Brandel‡, Fabrizio Tagliavini‡ (* and ‡: these authors contributed equally). Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomized, double- blind, placebo-controlled trial. Lancet Neurology published online 2014 Jan 7.

Our news on the subject

Le développement du cerveau a une part d’aléatoire
The stochastic aspect of brain development
Although every person’s personality is the result of genetic and environmental factors, these are not the only factors at play. Bassem Hassan and his team at Paris Brain Institute have discovered that, in fruit flies (drosophila), individuality also...
05.12.2025 Research, science & health
Analyse MERSCOPE
New treatment pathways for brain malformation-linked focal epilepsy?
A study by Stéphanie Baulac’s team has revealed somatic mutations in different cell types in patients with type 2 focal cortical dysplasia. This disease causes drug-resistant epileptic seizures, for which the main treatment option is currently...
05.12.2025 Research, science & health
Un iceberg
The ICEBERG cohort, 10 years of collective scientific and medical mobilization
The ICEBERG cohort, initiated 10 years ago, is interested in studying factors predictive of the onset and progression of Parkinson’s disease.
05.15.2025 Research, science & health
La huntingtine est une protéine indispensable au développement embryonnaire, à la formation et au maintien du tissu cérébral.
Huntington's Disease: The Energy Hypothesis Gets Traction
Huntington's disease, a rare hereditary neurological disorder, is associated with an energy deficit that precedes the onset of symptoms and is closely linked to their progression. At Paris Brain Institute, Fanny Mochel and her colleagues are testing...
02.11.2025 Research, science & health
À la recherche de marqueurs d’imagerie dans la démence frontotemporale
Searching for Imaging Markers in Frontotemporal Dementia
Could exploring the relationships between different brain networks help us understand frontotemporal dementia (FTD)? This neurodegenerative disease, which progresses at varying rates, is often diagnosed late—when clinical signs are already severe. At...
01.07.2025 Research, science & health
Monocyte – un globule blanc qui se différencie en macrophage. Crédit : Université d’Edinbourg.
Discovery of a Macrophage Anomaly in Multiple Sclerosis
Certain patients with multiple sclerosis (MS) can partially regenerate myelin—the protective sheath that surrounds nerve fibers—which is damaged during the evolution of the disease. In studying how immune cells influence this remyelination...
12.19.2024 Research, science & health
See all our news