- Dr Thomas Friedrich, Principal Investigator
- Prof. David Conti, Co-Investigator
- Dr Alida Hayner-Buchan, Co-Investigator
- Prof. John Lehman, Co-Investigator
- Albany Medical College, Albany, USA
- Preventing PVAN by Inhibiting Enzymes in the Host-cell DNA-damage Response
The survival of kidney transplants between most individuals requires that the recipient receive immunosuppressive medication to prevent rejection of the transplanted kidney. These medications are termed ‘immunosuppressive’ because they inhibit the normal immune response that protects our bodies from foreign microorganisms and molecules. Immunosuppressive therapy has been a true lifesaver in terms of dramatically lowering the rejection rate of transplanted kidneys. Unfortunately, inhibition of the normal response makes the transplant recipient more susceptible to infection. Over the last decade there has been an increase in damage or loss of transplanted kidneys due to infection by BK virus. This virus initially infects over 80% of the population in childhood, but is controlled by the immune system and does not cause disease. In 5-10% of kidney transplant recipients, the immunosuppressive therapy allows BK virus to grow in the transplanted kidney, destroying cells required for normal kidney function. The resulting damage to the kidney is termed ‘Polyomavirus-Associated Nephropathy (PVAN)’. No safe and effective drugs to prevent the growth of BK virus and the development of PVAN have yet been identified but they are greatly needed.
The ultimate goal of this research project is to identify drugs that will be effective in preventing or treating PVAN. Recent research on viruses closely related to BK virus has shown that the growth of these viruses relies on specific enzymes in the kidney cell that are normally used to protect the cell’s DNA from damage. We have found that BK virus may also rely on these enzymes for optimal growth. Identification of compounds that block BK viral replication by inhibiting the cell’s DNA-damage response may provide a novel approach to the prevention of PVAN.