LONDON (Reuters Health) - Administering the autoantigen glutamic acid decarboxylase 65 (GAD65) to patients with early type 1 diabetes protects their ability to secrete insulin over 18 months, a new report says.
GAD65 autoantibodies are commonly present at diagnosis of type 1 diabetes, and they are found in 10% of patients with non-insulin requiring diabetes. Their presence suggests progression to insulin dependence.
To test the feasibility of using GAD65 to induce tolerance and suppress autoreactivity, Swedish firm Diamyd Medical conducted a phase II trial involving 47 recently diagnosed adult patients at the UMAS hospital in Malmo and St. Gorans Hospital in Stockholm, Sweden.
Patients were divided into four dose groups -- 4, 20, 100 and 500 micrograms. In each group, 8 or 9 patients received the drug, and 3 or 4 placebo.
The company presented early results from the trial at the American Diabetes Association meeting in June last year. They showed that patients in the 20-microgram group had increased fasting and meal-induced C peptide levels after 6 months.
Longer-term findings were presented Monday at the Immunology of Diabetes Society meeting in Cambridge, England. The findings of the 18-month long clinical trial confirm the drug’s efficacy in improving the patients’ ability to produce insulin, Diamyd’s Chief Information Officer Johannes Falk told Reuters Health.
“Such long-term improvement in insulin production after the diagnosis of diabetes is quite remarkable,” said Daniel Kaufman, from the University of California, Los Angeles, whose research team first developed the drug in mice.
The researchers also found that the drug boosted levels of autoreactivity-suppressing CD4+CD25+ lymphocytes, an increase that correlated with clinical improvement.
“This provides important new insights into how to control the autoimmune responses that cause type 1 diabetes,” said Anders Essen-Moller, president and CEO of Diamyd Medical in a statement. “The study also shows that the drug is safe and that it is possible to inhibit the autoimmune attack on the cells that make insulin, thereby slowing the progression of the disease.”
He added that the company is hopeful that the drug will also be effective when given at earlier stages of the disease process. “We now know that type 1 diabetes takes years to develop and that we can identify people who are at early stages of the disease process by testing for autoantibodies in their blood,” he said.
Essen-Moeller told Reuters Health that the maximal benefit was seen at the 20-microgram dose. C-peptide levels increased roughly 50% and were sustained over 18 months, and blood glucose values improved, he said.
“It was met with great applause at the meeting,” he said in a telephone interview from Cambridge, “because I don’t think this has happened before. It was just two shots, and 18 months later they still didn’t need insulin.”
The Swedish firm is in discussions with bigger pharmaceutical players to look at how to take the drug into phase III, he said.
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