Using your own body’s immune system to treat type 1 diabetes?
Statistics from Diabetes UK reveal that in the UK alone, more than 1 in 17 people have diabetes whether it is diagnosed or undiagnosed. In 2013, 3.2 million people in the UK had diabetes and it is estimated that the number will rise to 5 million by 2025. By the year 2040, there will be 640 million across the world living with the condition.
There are several different types of diabetes but the ones that people are normally familiar with are type 1 diabetes (accounts for about 10% of all diabetics) and type 2 diabetes (accounts for up to 90% of all diabetes cases). Type 1 diabetes develops when the insulin-producing cells in the pancreas (called beta cells) have been destroyed. It is still not known why these cells get destroyed but the most likely cause quoted in scientific literature is that the body itself mounts an “immune response” and attacks its own beta cells. The trigger is unknown but several environmental and lifestyle stressful situations have been proposed. Currently, type 1 diabetes is treated with several daily insulin injections, across the whole of the diabetic’s life. This is incredibly hard on young children who have to learn from an early age that they have to inject insulin forever. Whilst stem cell therapy seems like an exciting solution for the future treatment of type 1 diabetes, due to the lack of human donors (where beta cells would be obtained from), it is still a distant dream. Another viable solution would be to grow beta cells in the laboratory to overcome this problem and many scientists around the world are currently trying to develop this technology.
Type 2 diabetes usually appears in middle-aged or older people, although it is now frequently being diagnosed in younger overweight people. In type 2 diabetes, beta cells are still able to produce insulin for a number of years, but because this is overproduced (to compensate for increased glucose levels in the blood), tissues in the body become resistant to its effects. Currently, weight loss is one of the first prescribed therapies for treatment of type 2 diabetes followed by oral medications.
So when a news article got published in Telegraph a few days ago entitled “End of daily injections for diabetes as scientists restore insulin production”, we all got incredibly excited! No more daily injections for millions of type 1 diabetics sounds like a dream come true! Could it be possible? What did the study report?
The published study reported phase 1 clinical trial data from two research centres, one at the University of California, San Francisco, and the second at Yale University. They used 14 patients with newly diagnosed type 1 diabetes and isolated their own immune cells (called regulatory T cells) and cultured them in the lab. The same cells were then expanded (increased in number) and infused back into individual patients in a dose-escalation manner (starting with the lowest dose and increasing it after not observing side effects). The patients were followed-up for around 31 months and whilst there were no major side effects observed, one patient did present with several episodes of hypoglycaemia (low blood glucose levels) and another with diabetic ketoacidosis. The scientists then measured the levels of C-peptide in these patients, as this could help them establish how much of their own natural insulin a person is producing (C-peptide rather than insulin is measured in the clinic, as this allows the doctors to distinguish between the ability of patients to still produce some of their own insulin versus the insulin that they may be injecting due to their diabetes). They found that the C-peptide responses were overall unchanged up to 2 years post-infusion. Some patients in the higher infusion group had a decline of more than 50% in C-peptide, but due to the low number of study participants, the scientists were not able to draw any conclusions in regards to the effectiveness of their treatment in further deterioration of diabetes.
The main success of this study is that it demonstrated that the patients’ own T regulatory cells could be grown and expanded in culture and that they survived well; moreover, no serious side-effects were associated with the infusion of these cells back into patients thus allowing for larger scale human studies. However, in the age of personalised medicine where we are trying to tailor each person’s medication on the basis of their responses to individual treatments, we are still a long way from understanding if this therapy is viable or of use to diabetics who might have been living with the disease for a number of years (not just newly diagnosed). Also there was no mention that insulin injections for these patients stopped as the Telegraph headline suggested.
However, any new knowledge in basic sciences that will help us understand how the body’s immune system attacks itself to result in diabetes is a step closer to a potential cure.
Bluestone, J. A. et al. (2015). Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Science Translational Medicine. DOI: 10.1126/scitranslmed.aad4134