News Article
GAD Immunotherapy May Help Preserve Insulin Secretion in Type 1 Diabetes
Immunotherapy with glutamic acid decarboxylase may help preserve residual insulin secretion in children with recent-onset type 1 diabetes, according to a report published online Oct. 8 in the New England Journal of Medicine.
Two injections of GAD-alum, the recombinant human 65-kD isoform of GAD in a standard vaccine formulation with alum, slowed the decline of C-peptide levels for up to 30 months in a randomized, controlled trial involving 70 children with recent-onset disease. However, the treatment did not change patients' insulin requirements, plasma glucose levels, or glycated-hemoglobin levels.
"Our results provide preliminary proof of concept; large-scale confirmatory studies with GAD-alum are under way in Europe and the United States," said Dr. Johnny Ludvigsson of Linköping (Sweden) University and his associates.
The investigators conducted the trial, which was sponsored by Diamyd Medical, because preliminary studies showed that the autoantigen GAD could prevent or slow the progression to hyperglycemia in prehyperglycemic mice. They assessed patients aged 10-18 years who had been diagnosed as having type 1 diabetes within the preceding 18 months. All the subjects had preexisting GAD autoantibodies, and all had residual insulin secretion at baseline.
Half the study subjects were randomly assigned to receive subcutaneous injections of GAD-alum (20 mcg) and half to receive placebo injections on days 1 and 30 of the study. The fasting C-peptide level, a marker of residual insulin secretion, was assessed at the 15-month follow-up. After the study was unblinded, the subjects were followed for an additional 15 months.
The GAD-alum therapy did not affect the fasting C-peptide level at 15 months, but did slow the decline in stimulated C-peptide level. At 30 months, both fasting and stimulated C-peptide levels showed a significantly smaller decline in the treated group than in the placebo group.
This protective effect was confined to patients who received the treatment less than 6 months after diagnosis, Dr. Ludvigsson and his associates said (N. Engl. J. Med. 2008 Oct. 8 [doi:10.1056/NEJMoa0804328]).
The duration and magnitude of effect of the GAD-alum injections were similar to those reported for another experimental immunotherapy, anti-CD3 treatment. However, unlike that treatment, GAD-alum was not accompanied by any adverse treatment-related effects, the investigators noted.
In particular, no patients showed any adverse neurologic reactions to the elevation in GAD autoantibodies induced by GAD-alum injections. There had been a concern that the rise in autoantibodies might cause stiff-person syndrome, a disabling disorder thought to be related to the presence of these antibodies in the central nervous syndrome.
Two of the investigators disclosed ties to Diamyd Medical.
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