New research at the Seattle Children’s Research Institute’s Center for Immunity and Immunotherapies could result in a treatment against type 1 diabetes that has long-term efficacy and removes the need for insulin injection.

The authors plan to carry out a clinical trial with human patients at Seattle Children’s to test the treatment’s merits.

No more friendly fire

“What started as a dream is now within reach,” said Dr. David Rawlings, director of the center and corresponding author of the paper.

“My hope is that our research will lead to a new treatment that turns off the destructive immune response leading to the development of type 1 diabetes in children.”

Insulin production is handled by islet cells in the pancreas. Malfunctions in our bodies’ regulatory T cells (Treg) can cause the immune system to see them as threats, and attack. Treg cells work to organize and control effector T cells, which are the ones who actually carry out the attacks.

If enough of these cells are damaged, the pancreas becomes unable to regulate glucose levels in the blood, causing the early symptoms of type 1 diabetes such as frequent urination, unquenched thirst, insatiable hunger, and extreme fatigue. Current treatments require daily insulin injections, without which the disease can become fatal.

In a bid to find a treatment that doesn’t require the logistics of insulin production and supply, the team details how Treg cells of patients can be genetically engineered to function like their normal counterparts. Their approach targets the FOXP3 gene, which governs the process by which T cells can mutate into Treg cells.

In theory, once injected back into a patient, these cells (‘edited regulatory-like T cells’, or ‘edTreg’) should enter the pancreas and help keep the immune system in check.

The team notes that these edTreg cells look very similar to natural Treg ones, and that they behaved like them during tests in tissue samples and on animal models. They are currently working to start a phase 1 clinical trial of their therapy.

“This data offers the first proof that engineering by way of turning on FOXP3 is sufficient to make a functional Treg-like cell product,” said Dr Rawlings. “Not only is it a landmark research finding, but it’s directly translatable to clinical use.”

While all of this is going on, the authors are further refining the efficiency of their treatment and to devise a way to make edTreg cells target the pancreas directly.

The paper “Gene editing to induce FOXP3 expression in human CD4+ T cells leads to a stable regulatory phenotype and function” has been published in the journal Science Translational Medicine.