Link between ALS and type 2 diabetes could offer new therapies

Link between ALS and type 2 diabetes could offer new therapies
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New research has highlighted links between amyotrophic lateral sclerosis and type 2 diabetes.

Patients with amyotrophic lateral sclerosis (ALS) often suffer from type 2 diabetes. This phenomenon has since long remained mechanistically enigmatic. Now, researchers at Karolinska Institutet in Sweden have identified a molecular mechanism linking ALS and type 2 diabetes.

The researchers found that immunoglobulin G (IgG) antibodies in the blood of ALS patients target the calcium channel in the cell membrane of the insulin-secreting beta cells in the pancreas.

Dr Yue Shi, first author of the study and Postdoctoral researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet, said: “This leads to an unphysiological calcium (Ca2+) influx and consequent beta cell death.”

The study is published in the scientific journal PNAS.

New therapies

Altered humoral immunity, i.e. the presence of autoantibodies targeting the body’s own cells, is a known phenomenon in type 1 diabetes.

The new study highlights the presence of autoantibodies as a pathogenic mechanism in a subgroup of patients with type 2 diabetes.

Dr Shao-Nian Yang, Associate professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior author of the study, said: “We now demonstrate that IgG from ALS patients with type 2 diabetes behave like cytotoxic autoantibodies, suggesting that altered humoral immunity can serve as a critical pathogenic mechanism in the development of diabetes.

“This may lay the foundation for a new immunotherapy strategy for patients suffering from both ALS and diabetes.”

Neurodegenerative diseases

The researchers believe that the presence of autoantibodies may be a generalised phenomenon for other neurodegenerative diseases as well.

Similar to ALS patients, a proportion of patients with disorders like Alzheimer’s disease, Parkinson’s disease and multiple sclerosis also suffer from type 2 diabetes.

Professor Per-Olof Berggren, Director of the Rolf Luft Research Center, Karolinska Institutet, and another senior author of the study, said: “Interestingly, pancreatic beta cells and neurons are equipped with similar types of calcium channels and share a series of physiological and pathological mechanisms for their function/dysfunction and survival/death, such as Ca2+-dependent exocytosis and Ca2+-triggered cell death.

“The extent to which the pathogenic mechanism that we discovered in patients with both ALS and type 2 diabetes may be generalised to other neurodegenerative diseases associated with diabetes will be the focus for future studies.”

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