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Cambridge Neuroscientists part of IMPRiND consortium

Blocking aggregate propagation in neurodegenerative diseases IMPRiND – Inhibiting Misfolded protein Propagation In Neurodegenerative Diseases – is an international consortium that aims to map and target critical steps in the propagation of misfolded tau and α-synuclein, considered the main culprits of neurodegeneration in Alzheimer's and Parkinson's disease respectively.Their plans are built upon:

 

  • Identify disease-relevant misfolded assemblies, imprint their biological properties in vitro and/or in cellulo and generate homogeneous populations in order to assay and interfere with their pathogenic effects.
  • Develop and miniaturise assays to monitor up-take, secretion, clearance and oligomerisation using bimolecular fluorescence complementation of oligomeric species or transfer of untagged assemblies to fluorescently labelled fibril-naìˆve cells and measure markers of early proteotoxicity that are suitable for high throughput or high content screens.
  • Perform genetic screens based on disease-relevant gene/protein networks and assess druggability of identified targets.
  • Deliver robust validation assays for these molecular events in complex cellular systems with greater functional resemblance to the native milieu of the brain such as iPSC-based models and organotypic cultures or simple model organisms such as Drosophila orzebrafish.
  • Improve existing animal models in order to standardise pathological readouts for in vivo validation of modifiers, correlate them with novel peripheral or in situ markers using microdialysis to accelerate the assessment of therapeutic interventions and relevance to humans, e.g. by transplantation of human iPSC neurons in animals.

 

The IMPRiND consortium will construct this entire pipeline to examine the propagation of α-synuclein and tau and test their tractability against disease progression. IMPRIND started in March 2017 and will run until February 2021. IMPRiND has a total budget of 11.4 million Euros. It is supported by the IMI with 4.7 million Euros, by industrial partners with 6.4 million Euros and 0.3 million Euros from the Swiss Federation. It comprises 18 partners in 7 European countries, including 6 universities, 5 research centres, 6 pharmaceutical companies and 1 SME specialised in scientific project management.

Cambridge Neuroscientists Maria Grazia Spillantini and Michel Goedert are members of the consortium. For more information, please see the website.   

Posted on 19/10/2017

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