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Old diabetes drugs offer hope for a new Hepatitis C treatment

11 Jun, 2010

ResearchBlogging.org

Metformin pills. Image credit: Flickr/[AJ]

Metformin pills

Researchers have found that drugs currently used to combat diabetes and obesity could also help fight Hepatitis C infection.

Hepatitis C is a disease of the liver. It is estimated that three per cent of the world’s population are affected, with four million carriers in Europe alone. Only around 40 per cent of sufferers will fully recover, with the others developing cirrhosis (degeneration of liver cells) and, in many cases, liver cancer.

Professor Mark Harris of the University of Leeds and colleagues study the effect of the Hepatitis C virus on human cells. Their research has led them to AMP kinase (AMPK), an enzyme that helps to conserve the energy balance in cells.

AMPK works by temporarily shutting down the production of fats when it senses an increase in energy requirements from the body. The team theorised that if the virus is replicating in a cell – making it do lots of things it wouldn’t normally do – this would increase the cell’s energy requirements. The cell would then try to respond by activating more AMPK.

“The cell would sense the increase in energy required to enable the virus to replicate,” said Professor Harris. “In such cases, AMPK would shut down certain functions of the cell temporarily until the cell’s energy is rebalanced.”

To test this, the team conducted tests on liver cells infected with hepatitis C virus, monitoring AMPK levels. But what they found was the opposite.

The Hepatitis C virus actually switched off AMPK so that the cell continues making lipids and membranes, both of which are vital to its survival.

This led the researchers to wonder: what would happen if they stimulated AMPK in the infected cells? A scan of the scientific literature revealed a plethora of currently used drugs that do just that. The team tested three, including Metformin and AICAR, two commonly used drugs used to treat type 2 diabetes and obesity. They found that not only were the drugs able to overcome the virus but also that they successfully halted virus replication, enabling the cells to clear the infection.

Though clinical trials are needed to establish whether this would work in patients, it’s a novel treatment that could be available relatively quickly. The drugs are already on the market – Metformin is one of the most commonly prescribed drugs in the world – and have already been approved for safety. This would greatly reduce the amount of time usually required to get a new treatment approved.

Professor Harris anticipates that this could form a supplementary treatment for Hepatitis C. The current front line therapy is Interferon/ribavirin. While it’s unlikely that AMPK-acting drugs would displace that, the fact that they have already been proven safe means they could potentially be used in a combination therapy similar to the way many HIV treatments are used.

The researchers are currently screening many of the other AMPK-stimulating drugs on the market, while also examining the exact mechanism of action between the virus, AMPK and the drugs further downstream. However, their main focus is a small clinical trial of around 30 patients in collaboration with the University of Nottingham. This will examine whether a few weeks Metformin has any effect on virus levels in patients.

  • Mankouri, J., Tedbury, P., Gretton, S., Hughes, M., Griffin, S., Dallas, M., Green, K., Hardie, D., Peers, C., & Harris, M. (2010). Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0912426107
  • Image credit: [AJ] on Flickr

    2 Comments leave one →
    1. Keith permalink
      16 Sep, 2010 2:04 pm

      I have had HCV for 30 years, and never received any treatment. Taking Metformin 500mg 2x daily for 3 years. RNA Viral Load has mysteriously dropped to 3 million. Not good, but not the worst. ALT 30 AST 80 Please keep me advised of your research. Many Thanks ! Chers !

      • sunny white permalink
        23 Mar, 2011 2:29 pm

        wonderful i have hep-c also and now taking metformin for diabetes i was just dx with..

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