Novel Diagnostics for Liver and CNS Diseases

Chronic liver disease is marked by gradual destruction of the normal liver tissue architecture in response to injury or an insult. Liver fibrosis is a condition where hepatic stellate cells (HSCs), normal resident liver fibroblasts, get activated into myofibroblasts and generate scarring or accumulation of extracellular matrix protein in the liver. Fibrosis is a reversible process; however, excessive scarring in the liver leads to cirrhosis, which in the absence of organ transplant, results in morbidity and mortality. It has been proven that stimulating apoptosis of activated HSC can resolve fibrosis and enhance the liver's response to chronic damage.

Using a fluorescently labelled recombinant human monoclonal antibody targeting the extracellular portion of Synaptophysin, we have shown specific localisation in the regions of liver where scarring were present. Synaptophysin is a plasma membrane protein expressed in activated HSCs. In mouse models of liver fibrosis, this antibody with its modest binding affinity, readily and selectively targeted liver myofibroblasts and showed minimal binding to non-fibrotic liver and any other tissue including kidney and brain. Monoclonal antibodies with improved affinity towards the same antigen target are being generated through animal immunisation. Along with conventional sheep immunisation, we are also exploring the potential of using chicken as the animal of choice for generating high affinity antibodies against mammalian antigens. 

Synaptophysin is also expressed on neural cells and plays an important role in the pathogenesis of various diseases of the central nervous system (CNS). This protein has been shown to decline in a variety of diseases including diabetes and Alzheimer's disease (AD). We are developing an anti-Syn antibody based molecular imaging agent which can be effectively used as a safer and non-invasive system for accurate diagnosis of liver fibrosis, neurodegenerative disorders including AD and conditions such as MS and stroke.

Project Team – Prof Andy Porter, Prof Matteo Zanda, Dr Soumya Palliyil

Project Funding – SULSA