Syedia Rahman, final year PhD student in the FRAME Laboratory, has been successful in getting her research article focused on integrins as a drug target in liver fibrosis published in leading journal, Liver International.

The paper was published on 20 January 2022 and summarises the research currently being conducted into integrins and their potential to help treat liver fibrosis. As the lead author of the paper, Syedia’s research was supported by the National Institute of Health Research Nottingham Biomedical Research Centre and part-funded by GlaxoSmithKline.

The liver is a key focus of the FRAME Laboratory’s research, as the worldwide incidence of chronic liver disease continues to increase and there is a growing and urgent need for effective treatments. Recent research has suggested that integrins, which are proteins that are present on all cells, have the potential to be a promising target for liver fibrosis. The αv integrin group has been shown to be central in the development of liver fibrosis, however, its relative importance is not understood.

Syedia’s review summarises the current knowledge of the different αv integrins in different organs and looks at the data emerging from different laboratory disease models and clinical trials with regards to the different αv integrin drugs in development for the treatment of liver fibrosis. The paper will be a useful resource for researchers studying integrins as a potential treatment for diseases such as liver fibrosis, as well as those working in drug development for the treatment of liver fibrosis.

Therapeutic targets for liver fibrosis

The paper identifies that there are currently not any available, approved treatments for liver fibrosis, and that the current drugs in development are not directly targeting the fibrosis process. It finds that some αv integrins are central to the development of liver fibrosis and have the potential to be a promising drug target, however, their specific role is not yet fully understood. Moreover, there are laboratory disease models using αv integrin drugs that have shown certain αv integrins to be a potential target in various fibrotic diseases including liver fibrosis. However, the same results have not been seen in clinical trials, emphasising the need for more data to be collected from human disease samples, as most disease models use animals.

The paper recognises that there is progress being made through various investments from pharmaceutical companies in which some αv integrin drugs have entered the early phases of clinical trials. It argues that studies exploiting the expression of specific αv integrins and their presence within both diseased tissue and healthy tissue using human models are crucial to determine and develop more successful therapeutic targets for liver fibrosis.

The need for human disease models

Syedia’s research findings indicate that animal disease models do not replicate the process of liver fibrosis effectively enough for treatments to be developed, highlighting that research using human models could be better translated from early laboratory work to clinical trials.

The FRAME Laboratory’s research into non-animal models for the liver and liver disease is ongoing, and Syedia’s own PhD looks at the use of hepatic stellate cells (HSCs) – the primary effector cells in the development of liver fibrosis (scarring of the liver associated with liver disease) – and identifying the amount of integrin expression within them. She aims to provide further information that may help identify new, potential drug targets for liver fibrosis, in addition to offering insights into HSCs, integrin expression and liver fibrosis using a human model. This provides an alternative to using animals in science as most models for liver fibrosis typically rely heavily on the use of rodents.

About the FRAME Laboratory

The aim of the FRAME Laboratory is to produce human-based systems that are better and more relevant to humans than current animal models. The FRAME laboratory uses cells derived from human tissues to produce biologically relevant in vitro models of human organs, which behave and respond in the way they would in the body. Rather than growing cells as a single layer on plastic surfaces, the lab uses three-dimensional scaffolds and introduces flow into these systems to replicate the environment found in living humans. Current cell models include human liver, skeletal muscle, adipose tissue, and skin.

Find out more about the FRAME laboratory’s liver research. 

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