Skip to main content

Or 34,00 After 66% tax deduction

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

A new model for therapeutic research in Creutzfeldt-Jakob disease

Published on: 17/11/2021 Reading time: 1 min
image

What if a worm allowed a quantum leap in research on prion diseases such as Creutzfeldt-Jakob disease? A recent study by Nicolas Bizat (University of Paris) and Stéphane Haïk (Inserm) at the Paris Brain Institute, published in the journal Brain, suggests the potential of this model for therapeutic research and identifies five promising molecules for these diseases.

Human prion diseases are fatal neurodegenerative disorders that include sporadic, infectious and genetic forms. Inherited Creutzfeldt-Jakob disease due to the E200K mutation of the prion protein-coding gene is the most common form of genetic prion disease. The phenotype resembles that of sporadic Creutzfeldt-Jakob disease at both the clinical and pathological levels, with a median disease duration of 4 months. To date, there is no available treatment for delaying the occurrence or slowing the progression of human prion diseases. Existing in vivo models do not allow high-throughput approaches that may facilitate the discovery of compounds targeting pathological assemblies of human prion protein or their effects on neuronal survival.

Here, we generated a genetic model in the nematode Caenorhabditis elegans, which is devoid of any homologue of the prion protein, by expressing human prion protein with the E200K mutation in the mechanosensitive neuronal system.

Expression of E200K prion protein induced a specific behavioural pattern and neurodegeneration of green fluorescent protein-expressing mechanosensitive neurons, in addition to the formation of intraneuronal inclusions associated with the accumulation of a protease-resistant form of the prion protein. We demonstrated that this experimental

system is a powerful tool for investigating the efficacy of anti-prion compounds on both prion-induced neurodegeneration and prion protein misfolding, as well as in the context of human prion protein. Within a library of 320 compounds that have been approved for human use and cross the blood–brain barrier, we identified five molecules that were active against the aggregation of the E200K prion protein and the neurodegeneration it induced in transgenic animals.

 

This model breaks a technological limitation in prion therapeutic research and provides a key tool to study the deleterious effects of misfolded prion protein in a well-described neuronal system.

Image d’un nématode (C. elegans) exprimant la protéine prion humaine dans le système mécanosensitif (vert)
Image of a nematode (C. elegans) expressing the human prion protein in the mechanosensory system (green)

Sources

https://pubmed.ncbi.nlm.nih.gov/34687213/
Bizat N, Parrales V, Laoues S, Normant S, Levavasseur E, Roussel J, Privat N, Gougerot A, Ravassard P, Beaudry P, Brandel JP, Laplanche JL, Haïk S.Brain. 2021 Oct 22;144(9):2745-2758.

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