Rebalancing the Immune System to Fight Type 1 Diabetes

Type 1 diabetes develops when the immune system destroys the insulin-producing cells in the pancreas. While conventional therapies usually only take effect after the onset of the disease, a research team from Helmholtz Munich, the German Center for Diabetes Research (DZD) and Goethe University Frankfurt is investigating a novel drug that acts earlier. Vidofludimus calcium, which is already being tested for multiple sclerosis, could help to prevent type 1 diabetes by restoring balance to the immune system and stopping the misdirected immune response. The findings were published in 'Molecular Metabolism'.

Type 1 Diabetes (T1D) is a chronic autoimmune disease that destroys insulin-producing beta cells in the pancreas, resulting in lifelong insulin dependence and serious health complications. While early diagnosis can help manage the disease, researchers are urgently seeking treatments that can go beyond symptom management to slow or stop disease progression.

A New Target: Immune Cell Metabolism

In a collaborative effort, researchers from the German Center for Diabetes (DZD) at the Research Unit Type 1 Diabetes Immunology (TDI) at Helmholtz Munich, together with scientists from the Goethe University Frankfurt, have identified a promising new therapeutic approach. Their study demonstrates the potential of vidofludimus calcium, a next-generation immunomodulatory drug, to alter the course of T1D by blocking a key metabolic pathway in immune cells.

Vidofludimus calcium, currently in phase 3 clinical trials for multiple sclerosis and developed by Immunic Therapeutics, selectively inhibits the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme plays a critical role in pyrimidine synthesis, which is essential for the proliferation of rapidly dividing immune cells involved in autoimmunity.

Immune Modulation in Preclinical Models

In two different pre-clinical mouse models of T1D, treatment with vidofludimus calcium significantly reduced disease incidence. On the cellular level, the drug both decreased the activation of pathogenic T cells and increased the frequency of protective regulatory T cells (Tregs) – a subtype of immune cells crucial for suppressing autoimmune responses.

“With this publication we discover for the first time that inhibiting the enzyme DHODH fosters immune-protective Tregs during islet autoimmunity and delays the progression to overt T1D in pre-clinical models,” says Prof. Carolin Daniel, the corresponding author of the study.

Towards Immune-Based Disease Modification

These findings represent a critical step toward immune-modulatory therapies for T1D that go beyond symptom management to directly influence the underlying autoimmune response. By restoring balance between harmful and protective immune cells, such approaches could offer a way to slow or prevent the progression of autoimmune diabetes in at-risk individuals.

Source: DZD