A collection of all IMPRiND research highlights is now available for download. This document is a journey through the research results of the project over the last five years.
New scientific consensus has been established by the Cryo-EM characterisation of tau and α-synuclein filaments isolated or amplified from human brains. This work has led to a structure-based stratification of tauopathies and improved standards for the development of ligands or therapeutics (e.g. PET ligands, antibody immunotherapies or anti-aggregation molecules).
Importantly, the consortium has used highly characterized seeds and readouts of seeded aggregation to complete CRISPR-based and siRNA screens and identified modifiers of α-synuclein and tau aggregation in cell lines and primary neurons. These screens will become publicly available upon completion of the project and provide a rich source of data for Industry and academic partners interested in drug target discovery and development.
Elevation of p-Tau in CSF is linked to the aggregation of amyloidogenic proteins rather than a unique feature of β-amyloidosis and can occur independently of neurofibrillary tangles. Provocative and impressive findings from Stephan Käser from the DZNE team. https://doi.org/10.1007/s00401-021-02400-5
This paper from the LMB team presents Cryo-EM analysis of tau filament structures from a range of neurodegenerative diseases that suggests a new method for characterising tauopathiesRead more
Proteopathic brain lesions are a hallmark of many age-related neurodegenerative diseases including synucleinopathies and develop at least a decade before the onset of clinical symptoms. This work carried out by the DZNE team allows to better understand the initiation and propagation of such lesions, a key knowledge for developing therapeutics to delay or halt disease progression.Read more
Induced αS lesions in mouse and human brain cultures. This publication from the DZNE team shows that now we can study such lesions in a true aged human brain environment. A key finding for developing therapeutics to delay or halt disease progression.
IMPRiND partners UOXF and CNRS have now come up with a working laboratory model. They used induced pluripotent stem cells (iPSC) derived from both healthy subjects and patients with the alpha-synuclein gene defects to generate human dopaminergic neurons that are primarily affected in Parkinson’s disease. They found a way of ‘amplifying’ in a fairly pure form, the main constituent, called fibril, of alpha-synuclein clumps directly from post-mortem Parkinson’s brains. When they added these brain-derived fibrils onto the human dopaminergic neurons, they successfully triggered the aggregation of alpha-synuclein inside the cells and observed progressive neuronal loss.
A great IMPRiND achievement: Nature Comm. paper on α-synuclein strain effects in iPSC-dopaminergic neurons.
IMPRiND partner CNRS research shows diagnostic & therapeutic potential in the prion-like propagation of fibrillar aSYN, as they can facilitate the design of ligands that specifically bind & distinguish between fibrillar polymorphs. Read the publication.
IMI is organising a series of online live sessions on IMI’s Impact, where key actors will explore the challenges and demonstrate how IMI contributed. As part of this event a IMI impact on dementia Event will be organised on 15 June 2021, 2:00 - 4:00 CEST.
The event comprises of a series of presentations including a talk on NEURONET by our Project Coordinator Carlos Diaz. To learn more about the event
IMPRiND partners Tofaris (UOXF), Melki (CNRS), Bose (Lilly) and McEwan (LMB) will present at the International Festival of Neuroscience during the Symposium Protein aggregation in Parkinson's and Alzheimer's disease: from mechanisms to targets for therapies on Wednesday 14 April.
Today Erwan Bezard from the UBx team was interviewed on the topic of "The search for better animal models of
Alzheimer’s disease" by the leading online community for Alzheimer's & dementia patients & caregivers: Being Patient.
This interview will be featured in the next couple of weeks as part of their "Talk with experts" series.
A better understanding of the spreading of the aggregates of protein tau is key to be able to interfere with the progression of neurodegenerative disorders such as Alzheimer’s disease. The LMB team developed a new model of tau pathology that allowed them to follow this process and to get new insights into the behaviour of tau seeded aggregation in neural tissue.Read more
A great discussion today at the IMPRiND Symposium at #ADPD2021
This project receives funding from the Innovative Medicines Initiative 2 Joint Undertaking (www.imi.europa.eu) under grant agreement No 116060. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
This work is supported by the Swiss State Secretariat for Education‚ Research and Innovation (SERI) under contract number 17.00038.
The opinions expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.