Procedure offers hope in type 1 diabetes

New strategy proves curative in more than half of mice tested

Web edition : 2:44 pm

A three-pronged strategy ? to knock out renegade immune cells, replace them and revitalize other cells that make insulin ? might reverse type 1 diabetes. Scientists report in the May 9 Science Translational Medicine that seven of 12 diabetic mice treated with this combination were cured even after having lost the ability to make insulin for several weeks, the equivalent of a human patient who has needed insulin injections for a couple of years.?

Type 1 diabetes often strikes at an early age and relegates a person to a lifetime of blood sugar tests and insulin shots. The condition results when one?s own immune cells kill insulin-making cells called beta cells housed in the pancreas. A few of these beta cells usually survive, but don?t produce adequate insulin to process sugars.

In the new study, researchers used specially designed antibodies and other drugs in the mice to first wipe out rogue beta-cell killers from the immune system called CD3 and CD8 T cells.

The mice then received a mismatched bone marrow graft to replace the immune cells. The mismatch seems necessary to prevent the newly developing T cells from targeting beta cells, says study coauthor Miao Wang, an endocrinologist at the City of Hope Beckman Research Institute in Duarte, Calif. Recipient mice also got stripped-down T cells from the spleens of the mismatched donor mice. These cells may prevent a backlash effect called graft-versus-host disease in which transplanted tissue attacks its new host.

To restore insulin production by beta cells, the mice received hormone and growth-factor injections for 60 days.

The seven mice cured of type 1 diabetes regained about 20 percent of their normal supply of beta cells, which made enough insulin to fend off high blood sugar. The beta cells were a mix of old cells that began to multiply after treatment and new beta cells with mysterious origins. ?We believe there are pre-existing beta-cell progenitors inside the pancreas,? and these developed into new beta cells, says Wang.

The seven animals remained free of diabetes 150 days after treatments ended.

Currently in humans, the only cure for type 1 diabetes is a transplant of pancreatic ?islets? containing beta cells. ?It has many limitations,? Wang says. A single transplant typically requires multiple donors, and recipients need immune-suppressing drugs indefinitely, she says. Also, a 2006 report showed that two-thirds of islet transplant recipients were back on insulin injections within two years of the operation.

?If our therapy could successfully translate to humans,? Wang says, ?I think it could be a replacement for islet transplantation.?

Anita Chong, an immunologist at the University of Chicago, says the researchers might need to test the therapy in nonhuman primates to show that the first step will knock out the rogue CD3 and CD8 T cells. Also, scientists will need to ascertain whether the beta-cell boosters will work without adverse effects, she says.
Found in: Biomedicine and Body & Brain

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