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A novel NASH model for target and drug candidate identification

Objective

NASH is the progressive form of NAFLD that underlies the development of fibrosis, cirrhosis, and hepatocellular carcinoma. The global prevalence of NASH is estimated at 1 billion individuals. NASH is a major cause of death, now the major reason for liver transplantations and the disease is an important cause of hepatocellular cancer (HCC). Currently, there are no FDA-approved drug therapies available.

Within the ERC project Hepaspher, a new liver model was developed in which human hepatocytes and non-parenchymal cells are grown in a 3D spheroid structure that phenotypically closely resembles human liver in vivo with respect to transcriptome, proteome, and metabolome for up to 35 days. This model has proven to be of valuable use for the development and treatment of liver diseases such as steatosis, cholestasis, hepatitis, insulin resistance, and fibrosis.

In the SPHERO-NASH project, we focus on a more complex system whereby both inducers and mechanisms of NASH formation, drug-induced inhibition of NASH as well as studies of extracellular matrix (ECM) degradation including collagens and the role of ECM degradation control in the development and treatment of NASH can be studied. For this purpose HTS based screening in the SPHERO-NASH spheroid system will take place utilizing both siRNA target libraries and chemical inhibition libraries at HepaPredict AB with a proposed delivery of novel compounds/targets that can be further processed in drug developmental projects. We propose to commercialize the SPHERO-NASH model itself but also to commercialize targets and compounds found by siRNA and compound screening that regulate NASH formation and degradation. We aim to assess and demonstrate the commercial value to the pharmaceutical industry by building a strong knowledge transfer strategy. The SPHERO-NASH model thus has great fundamental and commercial potential in NASH drug discovery and development.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2023-POC

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Host institution

KAROLINSKA INSTITUTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 100 000,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (2)

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