Thursday November 20 2008
A leukaemia drug “could be used to prevent and even reverse type 1 diabetes”, according to The Daily Telegraph this week. The newspaper highlights results from a lab study on mice with diabetes, claiming that 80% given the drug imatinib went into remission.
The mice in this study have been specifically bred to develop diabetes, and while there are similarities between this mouse model and human diabetes, there may also be differences in the development of the condition.
Therefore it is unclear as yet whether this drug or similar drugs would have a similar effect in humans, as only human trials could answer this question. Also, as chemotherapy drugs such as imatinib have side effects, such as inflammation of the pancreas and liver, these would have to be weighed up against any potential benefits identified in human trials.
At present there are no treatments that can reverse the effects of diabetes in humans so any new treatments that could would be an attractive option.
Where did the story come from?
Dr Cedric Louvet and colleagues from the University of California conducted this research, which was funded by National Institutes of Health and the Juvenile Diabetes Research Foundation. The study was published in the peer-reviewed scientific medical journal, Proceedings of the National Academy of Sciences of the USA.
What kind of scientific study was this?
This was an animal study looking at the effect of drugs in mice specially bred to develop diabetes. Diabetes is an autoimmune disease, where the body attacks and kills the cells in the pancreas, so researchers thought a drug shown to improve other autoimmune diseases in mice might also improve diabetes.
The study was specifically interested in a class of drugs called small-molecule tyrosine kinase inhibitors. Two drugs of this type were tested in this study: imatinib, which is marketed as Glivec, and sunitinib, marketed as Sutent.
Imatinib is used to treat chronic myeloid leukaemia and a rare type of stomach cancer in humans. Sunitinib is used in humans to treat kidney cancer and the same type of stomach cancer as imatinib.
The researchers first wanted to investigate the effect of imatinib on the risk of developing diabetes. They used mice called non-obese diabetic (NOD) mice, whose immune system spontaneously starts to attack their pancreas by two to four weeks of age. NOD mice develop full blown diabetes by about 12 to 14 weeks of age.
They divided the NOD mice into two groups, and fed one group a dose of imatinib once a day for seven weeks, starting at 12 weeks of age, when the mice were essentially pre-diabetic. The other group received no imatinib.
The researchers measured the blood glucose levels of both sets of NOD mice to look at the proportion of mice in each group that went on to develop diabetes. They also repeated these experiments in normal mice (non-NOD mice) treated with a drug called cyclophosphamide, which causes them to develop diabetes.
The researchers wanted to look at the effect of imatinib on established diabetes. They took NOD mice that had recently developed diabetes and treated half of them with imatinib and left the other half untreated. The researchers measured the mice’s blood glucose levels to determine whether any of them were experiencing a remission. The researchers also repeated this experiment with sunitinib.
They also looked at what effect these drugs might be having on the immune system and various biochemical pathways.
What were the results of the study?
The researchers found that by 19 weeks of age none of the NOD mice treated with imatinib had developed diabetes, while about 40% of the untreated NOD mice had developed the condition.
After imatinib treatment was stopped, 20% of treated NOD mice had gone on to develop diabetes by 30 weeks, compared with 71% of the untreated NOD mice. Most of the treated NOD mice still had not developed diabetes by 50 weeks. They found similar results in normal mice treated with cyclophosphamide, a drug that induces diabetes in mice.
In the second part of the experiment, on NOD mice which had recently developed diabetes, imatinib caused a remission in about 40% of mice after one week of treatment. None of the untreated mice experienced a remission. If imatinib treatment was stopped after three weeks, all of the mice developed diabetes by 15 weeks.
However, if imatinib treatment was given for 10 weeks, most of the mice remained non-diabetic for up to 35 weeks, although there was a gradual increase in the proportion with diabetes over this period. The researchers reported similar findings with the drug sunitinib.
What interpretations did the researchers draw from these results?
The researchers concluded that using selective kinase inhibitor drugs offered a “new, potentially very attractive approach for the treatment of [type I diabetes]”, as well as other autoimmune diseases.
What does the NHS Knowledge Service make of this study?
This study has added to previous animal studies that have suggested a potential role for imatinib and similar drugs in the treatment of autoimmune conditions.
Although there are similarities between human diabetes and this mouse model, there may also be differences in the processes underlying the development of the condition. Only human trials will show if the drug would have a similar effect in humans.
Chemotherapy drugs such as imatinib also have side effects, such as inflammation of the pancreas and liver and these would have to be weighed up against any potential benefits.
Sir Muir Gray adds...
This is biologically plausible, but a long way from humans, at the moment.