Cell-Based Models for Neurodegeneration Study and Use in Screening

An EU Horizon 2020 Project: H2020-FTIPilot-2016-1


Project Summary

Objective: CENSUS will produce innovative cell-based products that transform neurodegenerative disorder drug discovery.

Societal challenge addressed: Neurodegenerative disorders due to neuron deficiency or dysfunction of the spinal cord/brain cells are destructive in nature. The regeneration of affected cells is impossible, resulting in irreversible neural damage. Neurological disorders outnumber diseases in other therapeutic areas, inflict higher treatment and loss-of-productivity costs than cancer, cardiovascular disease and diabetes combined, and are growing faster than any other disease class in the EU/US.

Clinical challenge: Neurodegenerative drug interventions are characterised by limited efficacy coupled with a high percentage of non-responders, and/or serious adverse effects. Thus, despite the high number of Central Nervous System (CNS) drugs under development, there are only a few treatments available for some neurodegenerative disorders. The shortage of effective treatments is largely due to an exceptionally high rate of late stage drug failure, with poor translation of promising preclinical studies from animal models to clinic.

Industrial: The Industry challenge is to mitigate the high risk of neurodegenerative drug development. Poor CNS drug success is a direct consequence of ineffective preclinical candidate selection. Animal models of human neurodegenerative disease have led to important advances in understanding of pathogenic mechanisms and curative approaches, but inherent genetic, developmental and anatomical differences between humans and animals can result in imperfect phenotypic correlations between animal models and human diseases.

Industry has met this challenge by investing in cell-based analysis, now the most common in vitro tool in preclinical drug discovery. But cell-based preclinical testing only becomes a solution if it accurately predicts subsequent candidate performance in a clinical situation. This requires that cells express tissue-specific functions under culture conditions, such that physiological relevance is maintained. Industry’s problem is that this typically require complex 3-dimensional (3D) culture models, whose assembly is technically-demanding, laborious, expensive and not easily reproducible. CENSUS will remove these barriers to neurodegenerative drug discovery and deliver the first fully-assembled 3D cell products into the marketplace.

The CENSUS project will provide a technical solution to this healthcare challenge which delivers industry-attractive positive-disruption of neurodegenerative drug discovery. The project will create, on an industrial scale, human cell models whose functions reproduce a disorder aetiology with consistent fidelity, and with utility that allows their use as preclinical screening tools. To achieve this, CENSUS will produce CNS cell models from a consistent, renewable source, in the form of induced pluripotent stem cells (iPSC); will manufacture 3D scaffolds in multiwell culture plates by micro-extrusion technology; to optimise scaffold functionality and control cell performance using innovative pepide chemistry; will supply fully functional models as pre-assembled, frozen products. Integrated scalable manufacturing will create an analytical platform that, uniquely, combines high predictive value and low cost with exceptional end-user convenience. These technical principles will subsequently be extended to other neurodegenerative disorder models, and should later be adaptable to other cell models and disease targets.

Project Partners:
AvantiCell Science Ltd: www.avanticell.com
Cellink AB: www.cellink.com
Phenocell: www.phenocell.fr
Tissue Click Ltd: www.tissueclick.com

Project Update:

A very successful meeting was hosted by Tissue Click in Brighton in October 2017 to discuss progress over the first year of the project. Partners were pleased to report that significant technical advances towards the creation of a human cell model for neurodegenerative disorder drug screening had been made. Namely; the production and characterisation of relevant iPSC cell banks, the standardisation of differentiation protocols for CNS cell production and functionalisation of the bioink scaffold for 3D cell culture. Cryopreservation protocols have been established and high neuroprogenitor cell recovery of cells frozen in 96 well plate, plug-and-play format, has also been achieved.

Outputs in Process of Exploitation

To be updated