A New Approach to Treating Type-1 Diabetes

Scientists look at low-dose aldesleukin

Researchers at the University of Cambridge in the United Kingdom have taken the first step towards developing a new form of treatment for patients with type-1 diabetes that, if successful, could mean an end to the regular insulin injections endured by people with the disease, many of whom are children.

In a study published in PLOS Medicine, the researchers used a drug to regulate the immune system with the aim of preventing a patients’ immune cells from attacking their insulin-producing cells in the pancreas.

The drug––aldesleukin, a recombinant interleukin-2––is currently used at high doses to treat certain types of renal tumors and skin cancers. At much lower doses, aldesleukin enhances the ability of regulatory T cells (Tregs) to stop the immune system from “losing control” once it has been stimulated and to prevent it from damaging the body’s own organs (autoimmunity).

Critical to this approach was to first determine the effects of single doses of aldesleukin on Tregs in patients with type-1 diabetes. To achieve this, the team monitored 40 participants with type-1 diabetes and found doses of aldesleukin that could increase Tregs by 10% to 20%. These doses are potentially enough to prevent immune cells from attacking the body, but not so much that they would suppress the body’s natural defenses.

The researchers also found that the absence of a response in some participants in previous trials may be explained by the daily dosing regimen of aldesleukin that was used. The current study suggests that daily dosing makes Tregs less sensitive to the drug. The authors recommend that aldesleukin should not be administered on a daily basis for optimal immune outcomes.

“Our work is at an early stage, but it uses a drug that occurs naturally within the body to restore the immune system to health in these patients,” said lead investigator Dr. Frank Waldron-Lynch. “Whereas previous approaches have focused on suppressing the immune system, we are looking to fine-tune it. Our next step is to find the optimal ‘Goldilocks’ treatment regimen––too little and it won’t stop the damage; too much and it could impair our natural defenses; but just right and it would enhance the body’s own response."

The researchers say that any treatment would initially focus on people who are newly diagnosed with type-1 diabetes, many of whom are still able to produce sufficient insulin to prevent complications from the disease. The treatment could then help prevent further damage and help patients to continue to produce a small amount of insulin for a longer period.

Source: University of Cambridge; October 11, 2016.