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Australia set to test insulin 'vaccine' for juvenile diabetes

Simon Grose

Canberra
Approach might train body not to attack its own cells.
A 'vaccine-like' approach to juvenile diabetes, set to be tested in a clinical trial in Australia, aims to test whether delivering insulin through the nose can keep the immune system from attacking the body's own cells.

Vaccines prime the immune system to attack invaders and protect the body. But in type 1 diabetes, it is the T cells that attack and destroy insulin-secreting beta cells in the pancreas.

In a phase 2 trial announced in December, Australian researchers are testing whether nasal insulin delivered to people at risk of type 1 diabetes can prevent the disease by training their immune systems to tolerate beta cells.

Edwin Gale, head of the diabetes research unit at the University of Bristol, says although it is too early to speculate on whether the approach can prevent type 1 diabetes, it could add to scientists' understanding of immune tolerance.

Calling the approach 'vaccine-like' has provoked some skepticism from experts who say vaccinating against an autoimmune disease is inherently contradictory.

Warwick Anderson, chief executive of Australia's National Health and Medical Research Council, which co-funded the trial, says the term is a bit of a misnomer. "That word 'vaccine' stuck early on, 'immune regulation' would be better."

That word 'vaccine' stuck early on, 'immune regulation' would be better."

Warwick Anderson
Australian National Health and Medical Research Council

Insulin administered via the nose or mouth stimulates the immune system via the mucosal lining but is not absorbed further and does not affect blood glucose levels. A phase 1 trial completed in 2004 found immune responses similar to those seen in mouse studies.

A significant increase in antibodies to insulin accompanied a decrease in T-cell response, the first demonstration of this effect in humans. Project leader Len Harrison, of the Walter and Eliza Hall Institute in Melbourne, says the approach is based on the phenomenon of mucosal tolerance first reported in the 1940s.

"It seems paradoxical because insulin antibodies are a marker for the disease, but there is no evidence that antibodies themselves cause damage to beta cells," he says. The more important thing, he adds, is that the method suppresses the immune response to insulin.

In a separate project, Matthias von Herrath is investigating whether those who have recently contracted the disease would benefit from a combination of nasal insulin and drugs to suppress the immune system.

"Our studies have shown that such combo-therapies are much more effective," says von Herrath, head of the Immune Regulation Lab at the La Jolla Institute for Allergy and Immunology.

Previous attempts to show mucosal tolerance in people with type 1 diabetes have all failed (Diabetes Care 27, 2348?2355; 2004). But those studies involved individuals with end-stage disease who received oral insulin.

Delivering insulin through the nose would prevent it from degrading before it reaches the mucosa, Harrison says. The phase 1 trial suggested that although the treatment does not eliminate the T cells that destroy beta cells, it might enhance the T cells that help make antibodies. "You would have a mixture, it's a balance between the good guys and the bad guys," Harrison says.

At least 13,200 relatives of people with type 1 diabetes will be screened in order to identify 264 participants at high risk. Results are expected in seven years.

Published online: 31 January 2007.