Precision Prediction & Precision Medicine
Although people with type 1 diabetes (T1D) currently have a good life expectancy, statistics for morbidity and increased mortality are still problematic. Delaying or even stopping the onset of the disease is still the Holy Grail of T1D research. Since T1D is an autoimmune disease, many developments have been in the field of immune therapy, manipulating immune mechanisms directly (e.g. using monoclonal antibodies). These therapies can have severe adverse events, risks and heavy treatment burden. Alternatively, the immune system can be modulated by applying autoantigens (like vaccines). However, many studies have not been conclusive, likely due to the heterogeneity of T1D disease process. The presence of certain autoantibodies seems to be haplotype-dependent, e.g. GAD65 autoantibodies are linked to the HLA DR3-DQ2 haplotype, whereas the appearance of insulin autoantibodies is associated with the HLA DR4-DQ8 haplotype.
Earlier aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy was developed to train the immune system to tolerate GAD65. The video below explains how the therapy works:
This therapy was initially tested in the Diagnode-1 study and shown to be well tolerated by patients after being injected directly into the lymph node, in combination with virtamin D supplementation. Subsequently it was reported in a meta-analysis that, after GAD-alum treatment, people with T1D carrying the HLA DR3-DQ2 haplotype showed significant preserved beta-cell function (i.e. C-peptide production) in a dose-dependent fashion. The aims of the Diagnode-2 study, reported here, were to:
The authors conclude