New research from Sweden, published in the journal PLOS ONE, suggests that an old cancer drug may prevent immune rejection of transplanted donor tissue or organs. The discovery could lead to new treatments for autoimmune diseases - like rheumatoid arthritis or type 1 diabetes - where the person's own immune system attacks the body.
The researchers, Senior Professor of Neurosurgery Leif Salford and colleagues from Lund University, were studying the effects of an old tumor drug, Zebularine, that was developed in the US in the 1960s.
The team works at the University's Rausing Laboratory and has been researching brain tumors for many years.
Salford says they discovered "by chance" that Zebularine "had completely unexpected effects on the immune system."
Lead author Dr. Henrietta Nittby explains:
"It turned out that Zebularine has the ability to subdue the reaction of the body's immune system. This could be important in situations where tissue or organs are transplanted. We also think it could be used to curb the body's attacks on its own tissue in autoimmune diseases, for instance type 1 diabetes or rheumatoid arthritis."
The team describes Zebularine as a "DNA demethylating agent" that switches on genes for making enzymes that suppress the immune system.
In 2004, a group of US scientists studying the drug's anticancer properties found Zebularine specifically targets tumor cells and is better at inhibiting cell growth and promoting gene expression in cancer cells.
For this latest study, the Swedish team transplanted pancreatic insulin-producing cell groups (islets of Langerhans) from healthy rats into two groups of rats made diabetic by streptozotocin injection. One group was treated daily with Zebularine, and the other group received no further treatment.
The rats treated with Zebularine survived for a significantly longer period than the untreated rats.
Dr. Nittby says:
"It is very interesting that we only treated them with Zebularine for two weeks, but the effects of the treatment could be observed throughout the 90-day follow-up period."
She says the team is excited by the findings because they suggest not only that the immune system in the treated rats was suppressed, but also the treatment was targeted. Plus, there were no signs of side effects.
The team is now refining the treatment so that dendritic cells, a specific group of immune cells, accept certain proteins under the influence of the drug.
Such an approach would mean they could target the treatment even more precisely, as Prof. Leif Salford explains:
"If we succeed with that, we believe it could be of clinical significance both to prevent rejection of transplanted organs and to stop the body attacking its own tissue in autoimmune diseases."
Should this prove possible, the team hopes a great number of patients will be spared from needing to have immune suppressing treatment all their lives.
The Hans and Märit Rausing Charitable Trust, the Lund University Hospital Funds and the Janne Troedsson Research Fund provided financial support for the study.