SPHERO-NASH | A novel NASH model for target and drug candidate identification

Summary
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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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101123215
Start date: 01-09-2023
End date: 28-02-2025
Total budget - Public funding: - 150 000,00 Euro
Cordis data

Original description

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.

Status

SIGNED

Call topic

ERC-2023-POC

Update Date

12-03-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2023-POC ERC PROOF OF CONCEPT GRANTS
HORIZON.1.1.1 Frontier science
ERC-2023-POC ERC PROOF OF CONCEPT GRANTS