A Personalized Diabetes Cure?

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A predictive test could tell researchers whether or not stem cell or islet cell transplant to ‘cure’ diabetes will work.

As a person who was temporarily cured of type 1 diabetes through an experimental islet cell transplant, I cope with a deep frustration from the failure of the experiment. It’s not only because the transplanted cells died and I returned to having diabetes. The also frustration arises because a definitive answer about the cause of the failure remains uncertain and elusive. Perhaps it was something I did. Perhaps it was the immunosuppression. Perhaps it was just bad luck. Perhaps, perhaps, perhaps.

Now, however, a researcher thinks that the results of a new clinical trial reveal a way of predicting whether or not the transplant I, and thousands of others, went through could have been successful before it even started. And that breakthrough, he says, could shift the paradigm in how stem cell and islet cell transplants are used to treat and possibly cure diabetes.

“This shows that when it comes to trying to ‘cure’ diabetes there might be no magic bullet,” says Bart Roep, Ph.D., the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes and professor/founding chair, Department of Diabetes Immunology at City of Hope, an independent research and treatment center for diabetes, cancer and other conditions. “It’s more likely there is not one broad fix for everyone. It could be that we need to tailor treatments to individuals on a case-by-case basis, if we want to be successful.”

Roep’s research strongly suggests that some people with diabetes are predisposed to benefit from stem cell transplants that replace insulin-producing beta cells—thus restoring function and, in effect, curing diabetes—and some other people are simply not predisposed to experience a benefit because of the composition of their immune system.

The conclusion comes as a result of looking at a stem cell clinical trial in Brazil. The subjects in the decade-long trial received autologous hematopoietic stem cell transplantation (AHSCT), which is an infusion of their own stem cells, to replace the immune system that had attacked the insulin producing beta cells. The results varied greatly, according to a news release from the City of Hope.

“Twenty-one T1D patients who received AHSCT were monitored and assessed every six months,” the release said. “Most patients became insulin-free for an average of 3.5 years after transplantation, and C-peptide levels (an indicator of insulin production) remained higher than initial values for at least four years post-AHSCT, indicating temporary immunological balance and preservation of insulin-secreting beta cells.” 

Roep said there’s one subject who is still insulin-free nine years after being infused with stem cells in the trial.

“One boy has not taken insulin since he was 14 years old, and he is now 23 years old,” Roep says. “No one likes to use the word ‘cure’ when it comes to diabetes. We prefer ‘insulin independent,’ but, if that’s not a cure, I don’t know what is.”

Additionally, the trial, which Roep calls “unprecedented and still unmatched,” resulted in a complete remission of diabetes without the use of donor beta cells. The therapy studied in the Brazilian trial is, more importantly, also a therapy that does not require any follow-up immunosuppression, or other therapy, because the beta cells used are the subject’s own, Roep says.

But, there is also the conundrum of why some subjects in the trial remained insulin free longer than other subjects. That puzzle, however, took Roep’s research in a new direction that could end decades of frustration for researchers and subjects.

“We discovered the immune signature predicting these outcomes in the trial — either favorable or not,” Roep says, “which is the first step toward personalized medicine in type 1 diabetes. We have a foot in the door.”

In other words, by running blood tests and examining signatures in each subject’s immune system, Roep discovered after the fact that some subjects in the Brazilian trial all along were predisposed to reject the stem cells or accept them. Roep says this kind of predictive testing is already being used in treating cancer

What this leads to for Roep is much more than merely developing a predictive test telling subjects and researchers whether or not stem cell or islet cell transplantation will or will not work. For Roep it opens the door to an entirely new way of considering how to administer such therapies.

“This is a way that we can start doing personalized medicine,” he says. “It’s not a question of whether or not to have the transplant, but maybe there’s a different kind of transplant, or different treatment after the transplant, that will make it more successful. Each patient should be considered as an individual, and not merely as another person getting the same treatment as many others and expecting it to work the same way.”

Roep says while he expects reluctance on behalf of the medical establishment to embrace such a change in thinking, he’s still optimistic.

“Surgeons and immunologists are not always on the same page,” he says with a laugh. “But, maybe they can change their ways and change how they use drugs and provide treatments. I’m not sure, but I’m hopeful, that this is enough data to make us more open minded.”

Perhaps.

 

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2 Comments on "A Personalized Diabetes Cure?"

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Linda Carberry

I have been diabetic for 32 years. I’m a brittle Diabetic and now found a good dr. and she put me on the pump I am going to bring the paper to her may 12th and always hope for the best.

rick phillips

Alex,

This type of research is also proceeding in the study of RA. There is a marker test to predict the viability of up to three types of immunosuppressant medications. It has not been adopted on a widespread basis, but it is available and could improve access to these medications.

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