Numbers of patients with liver disease numbers are increasing annually and the disease accounts for over two million deaths worldwide each year, creating a significant burden on healthcare systems. It is closely associated with other major healthcare challenges such as obesity, metabolic syndrome and diabetes, however the disease can progress to other life-threatening conditions such as liver cirrhosis (scarring) and cancer. The clinical and financial burden of liver disease is overwhelming, accounting for 5% of the total NHS budget, however there are currently no approved therapies to manage the condition.
Human liver models
The progression of liver disease is driven by chronic inflammation, however creating medicines which can target and treat this has proven challenging, in part because animal experiments do not accurately reflect what happens in humans. Over the past few years, Dr Ali Kermanizadeh, Lecturer in Toxicology and Clinical Biochemistry at the University of Derby, has developed a range of advanced multi-cellular human liver models which can mimic the different stages of liver disease development: healthy, steatosis and non-alcoholic steatohepatitis (NASH).
Getting the right drug to the right place
In collaboration with industrial partner InSphero, based in Cambridge, Dr Kermanizadeh has developed a novel nanomedicine drug delivery system for the treatment of liver disease. Nanomedicine is a relatively new medical approach which involves using materials at the nano scale (one-billionth of a metre), where a cocktail of drugs is packaged as ‘cargo’ and precisely targeted to the correct place, resulting in fewer side effects. These nanomedicines travel through the bloodstream to the liver where the cargo is released and acts to reduce liver inflammation. Dr Kermanizadeh found that the nanomedicine cargo can be slowly and sustainably released over time, meaning fewer invasive injections for the patient
Safe, efficient and animal-free
Excitingly, three of the nanomedicines tested were found to significantly reduce liver inflammation following treatment for 21 days, alongside lower numbers of the characteristic features of liver disease such as enlarged liver cells (hepatocytes).
A challenge often encountered during drug development for liver disease is damage (or ‘toxicity’) to liver cells, however there was almost no liver toxicity found when using these nanomedicines.
As an additional safety measure, the toxicity of the nanomedicines was assessed in human cell-based models of the gastrointestinal system and lungs. This test is usually carried out using animals to estimate the dose which could cause major adverse effects and the lowest dose which could cause death. Again, no toxicity was found in these cellular models following nanomedicine treatment.
The impact of this research
This research has helped to secure additional funding, enabling the work to develop and move forward into clinical trials. Dr Kermanizadeh plans to submit this work to several conferences in 2024 and hopes to publish two papers in high impact journals.