Can Immunotherapy Help With Diabetes

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A form of immunotherapy gaining ground as a way to treat childhood food allergies has shown promise in treating another rising scourge of children and young adults: Type 1 diabetes.

In a small but rigorous clinical trial, British investigators gave patients recently diagnosed with the metabolic disorder a truncated version of the chemical that gives rise to insulin.

After a quarter-century of failed efforts to treat diabetes with an immune therapy, the experimental treatment appeared to quell the immune system’s assaults on the body’s insulin-production machinery. The authors of the new study call their experimental treatment “an appealing strategy for prevention,” both in the earliest stages of Type-1 diabetes and in children who are at high genetic risk of developing the disease.

Over the trial’s 12-month duration, eight newly diagnosed diabetic subjects who got a placebo treatment required steadily increasing insulin doses to maintain glycemic control. As their immune systems progressively destroyed the pancreatic cells that normally produce the essential hormone, their daily insulin use grew on average 50%.

The 19 subjects who got the experimental immunotherapy, however, continued to produce their own insulin. Among the subjects who got the experimental immunotherapy, the need for added shots of the hormone did not escalate in the year following their diagnosis.

The different metabolic trajectories of subjects in the trial’s control group and its active arm were evident at three months — the earliest point at which a surrogate marker for insulin production was measured.

The report of the early-stage clinical trial, published Wednesday in the journal Science Translational Medicine, offers some preliminary reassurance that immunotherapy could be used safely in this growing population.

Researchers have been wary of pursuing the strategy in diabetes, worried that it could accelerate or strengthen the immune system’s attack on insulin-producing pancreatic cells, or cause dangerous allergic reactions. In the current study, injections of an immunotherapeutic agent caused no detectable worrisome response — not even redness or swelling at the site of injection — prompting the authors to declare its safety profile “very favorable.”

Recent years have seen progress in the bid to develop chemical mimics of allergens that train and reassure the defenders of the immune system rather than inflame and encourage them. The approach, called antigen-specific immunotherapy, has seen growing success in the treatment of allergies to common foods, such as peanuts, eggs and soy.

Similar to food allergies, Type-1 diabetes is an immune disorder — a disease in which the immune system misidentifies a harmless or even necessary agent (whether ingested peanuts or insulin-making cells in the pancreas) as a threat. The immune system’s assault not only can cause discomfort and danger in the form of itching, swelling or anaphylactic shock. In diabetes, it destroys a function that’s essential to the body’s ability to extract fuel from food and to keep freely circulating blood sugar from damaging organs and blood vessels.

Just as lab-produced chemical snippets of peanuts accustom an overactive immune system to the eventual introduction of real peanuts, the researchers hoped that the chemical flag they devised would teach the immune systems of newly diagnosed diabetics to recognize insulin and call off their attack on its source.

By using just a piece of the antigen that typically causes the immune reaction, the approach of such “peptide immunotherapy” aims to inure the immune system to the object of attack while avoiding a full-on allergic response.

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