A trial of a vaccine to prevent progression of type 1 diabetes has been unsuccessful. The findings are reported in an Article published Online First and coinciding with presentation of the study at the American Diabetes Association meeting in San Diego. The study is by Dr Jay S Skyler, Diabetes Research Institute, University of Miami Miller School of Medicine, FL, USA, and colleagues.
A successful diabetes vaccine would need to protect vital insulin-producing β-cells from auto-immune attack, without negatively affecting the rest of the immune system's functions and thus lowering immunity. Previous research has suggested that glutamic acid decarboxylase (GAD) is a suitable target antigen in type 1 diabetes.
In this study, the authors assessed whether several injections of 20 μg GAD formulated with the adjuvant alum (GAD-alum) would preserve insulin production in patients with type 1 diabetes who were treated within 3 months of diagnosis. The effect of the vaccine was measured by the production of C-peptide, which indicates the level of β-cell function.
A total of 145 patients aged 3-45 years who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and Canada, and randomly assigned to receive one of three treatments: three injections of 20 μg GAD-alum, two injections of GAD-alum and one of alum, or 3 injections of alum (as a control group). The researchers found that patients in all 3 groups had similar decline in β-cell function (similar C-peptide levels) and thus similar progression of their type 1 diabetes.
The authors conclude: "Although GAD vaccine was ineffective in recent-onset diabetes, the vaccine might be beneficial for prevention of type 1 diabetes if given earlier in the course of disease, or could be a component of a combination therapy protocol in recent-onset type 1 diabetes. Clearly, however, GAD vaccine should not be used in type 1 diabetes in clinical practice."
They also call for more research to test whether or not giving the vaccine earlier or making it part of combination therapy is effective.
In a linked Comment, Dr Chantal Mathieu and Dr Pieter Gillard, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium, say: "Most experts agree that combination therapy will be the solution, with combinations of immune modulating drugs or interventions (possibly including anti-CD3) at lower doses and an antigen-specific approach, why not GAD?"
They conclude: "Researchers should not give up hope of preventing or curing type 1 diabetes. The machinery exists to do the trials, as do the ideas and motivation. What is needed is the continued interest of agencies, pharmaceutical companies, and the scientific community in the quest to beat this disease."
Dr Jay S Skyler, Diabetes Research Institute, University of Miami Miller School of Medicine, FL, USA. Please e-mail first to arrange interview. T) +1 305-588-4447 E) jskyler@miami.edu
Dr Chantal Mathieu / Dr Pieter Gillard, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium. T) +32 16346994 E) chantal.mathieu@uzleuven.be / pieter.gillard@uzleuven.be
Journal
The Lancet