Publications

Precision Prediction & Precision Medicine

DIAGNODE-2: RESULTS FROM TRIAL WITH DIABETES VACCINE DIAMYD® (GAD65-ALUM) PUBLISHED

Johnny Ludvigsson, Zdenek Sumnik, Terezie Pelikanova, et al. (including Theo Sas of Diabeter)

Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

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:

 

  • Assess the efficacy (i.e. preservation of C-peptide production as proxy for beta-cell function) of three intralymphatic injections of GAD-alum in combination with vitamin-D supplementation
  • Perform a subanalysis of participants carrying the HLA DR3-DQ2 haplotype to see if GAD-alum treatment sows a different (higher) efficacy for this subgroup

Key findings:

  • For the whole cohort GAD-alum treatment showed no effect on the decrease of C-peptide production over time
  • In the HLA DR3-DQ2 haplotype subgroup there was a significantly slower decrease of C-peptide production compared with the placebo group
  • Effects of vitamin D were difficult to interpret
  • Regardless of haplotype, treated participants showed increased GAD-autoantibody levels after treatment
  • Participants carrying the HLA DR3-DQ2 haplotype showed an increased proliferation index and increased IL-10 and IL-13 levels compared with the placebo group
  • The treatment was safe: although about half of participants experienced any adverse event, there were only 3 serious adverse events and no physiological or neurological concerns were reported

 

The authors conclude

"Because modern medicine is about matching the appropriate drugs or treatments to the patient populations most likely to benefit from them, this finding is promising, and if confirmed in a larger clinical trial, it could pave the way for such a precision medicine approach in T1D." -

Please click here for the full-text pdf.

< Back


© 2019 Diabeter | Terms of Use | Privacy Statement