Results from a Phase 2 trial testing a novel type 1 diabetes vaccine have found the treatment is effective in a patient subgroup with a specific genetic variant. If validated in larger trials the new treatment could be helpful in around 50 percent of patients with type 1 diabetes.
For several years, researchers have known that one of the key indicators of type 1 diabetes is the presence of autoantibodies targeting a pancreatic protein called GAD65. In these diabetic patients the presence of these autoantibodies is often an early sign of disease and researchers have long hypothesized the possibility of disrupting this autoimmune mechanism as a way of helping prevent the destruction of insulin-producing cells.
To help the immune system become more tolerant of these natural GAD proteins, a vaccine called GAD-alum has been developed. If the immune system of a newly diagnosed diabetic patient could be trained to stop destroying GAD proteins, then hypothetically some level of natural insulin production could be retained. However, a number of GAD vaccine trials over recent years have delivered inconclusive results.
Researchers behind a Phase 2 trial testing a GAD vaccine in over 100 newly diagnosed young type 1 diabetes patients are suggesting a particular genetic variant could be the key to understanding who this treatment may work for.
Half of the cohort of 109 patients received three monthly GAD-alum injections, while the other half were administered placebo injections. Fifteen months later there was no overall difference in insulin production between the treatment and placebo groups. But, the researchers did detect a significantly positive effect in a subgroup of patients in the treatment group with a specific genetic variant.
Looking at a variant in HLA genes, called DR3-DQ2, the study detected a clinically significant preservation of insulin production after 15 months. Around 50 percent of all patients in the trial had this particular genetic variant.
“The patients in the subgroup with the DR3-DQ2 type of HLA genes did not lose insulin production as quickly as the other patients,” explains Johnny Ludvigsson, a researcher working on the study from Linköping University. “In contrast, we did not see any significant effect in the patients who did not have this HLA type.”
This new trial finding could help explain the inconsistent results from prior GAD vaccine studies. Ludvigsson also notes that while this positive treatment effect does not completely rescue all insulin-producing cells in a diabetic patient, it can help the body conserve some small level of insulin production, which can be significant in helping maintain safe blood sugar levels.
Larger trials will be necessary to validate these results, but Ludvigsson says this novel treatment could be helpful in around 50 percent of type 1 diabetes patients.
“Treatment with GAD-alum seems to be a promising, simple and safe way to preserve insulin production in around half of patients with type 1 diabetes, the ones who have the right type of HLA,” says Ludvigsson. “This is why we are looking forward to carrying out larger studies, and we hope these will lead to a drug that can change the progress of type 1 diabetes.”
The new study was published in the journal Diabetes Care.
Source: Linköping University
