A vaccine designed to combat type-1 diabetes mellitus (T1DM) has delivered promising results in a phase II clinical trial. Researchers at Stanford University School of Medicine trialled the DNA â€˜reverse' vaccine in 80 patients with T1DM and taking insulin, and found that in the vaccine group, levels of C-peptide (a proxy of insulin production) were maintained or even occasionally increased over the 12-week period. This would suggest that the vaccine, known as TOL-3021, might be effective in reducing ongoing destruction of the insulin-producing beta cells.
Beta cells produce a precursor protein of insulin called proinsulin, and a popular theory for the pathogenesis of T1DM is that CD8+ cells are triggered to attack beta cells that have proinsulin peptide fragments peppering their surface. The researchers hypothesized that an engineered DNA plasmid encoding proinsulin would reduce the activity of insulin-specific CD8+ T cells. The vaccine used in the trial consisted of DNA that contained a gene coding for the proinsulin protein, therefore reducing the frequency of CD8+ T cells reactive to proinsulin.
“We’re very excited by these results, which suggest that the immunologist’s dream of shutting down just a single subset of dysfunctional immune cells without wrecking the whole immune system may be attainable,” said Lawrence Steinman, MD, professor of pediatrics and of neurology and neurological sciences at Stanford. “The idea here is to turn off just the rogue immune cells that are attacking the pancreas and killing the beta cells that secrete insulin.”
The concept of shutting down a specific immune response rather than turning on a specific immune response makes the vaccine a new and very exciting concept. TOL-3021 is a lead product of Tolerion Inc, a newly formed clinical-stage biopharmaceutical company. Steinman says they are now eager to test TOL-3021 in a larger trial with longer dosing beyond 12 weeks. "We do want to look at treatment of children, and the ultimate would be to see if we can treat those at risk before they get the disease and do this in a preventive way," Steinman said.
Patients taking the vaccine maintained or even increased their levels of C-peptide in the blood which, alongside acting as a proxy for insulin, may also offer some additional health benefits. “Individuals with preserved C-peptide are at lower risk of long-term eye, kidney and nerve complications,” said JDRF’s Insel. “So it’s intriguing that in this study, C-peptide levels were preserved or, at times, increased while patients were receiving the vaccine.”
Type-1 diabetes mellitus affects as many as 3 million Americans.
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