By understanding what causes type 2 diabetes in Alström’s disease, researchers have discovered a new therapeutic target, the ALMS1 protein.
- Alström syndrome causes retinal degeneration, early obesity, and type 2 diabetes.
- The study of this syndrome allowed them to determine the role of a protein in the onset of diabetes, causing the fatty tissue abnormalities that cause type 2 diabetes.
- By restoring the functioning of this gene, the tissues can again assimilate glucose, and it is thus possible to regain a glycemic balance, therefore to treat diabetes.
Alström syndrome is a rare genetic disease: around 900 people are said to be affected by it worldwide. The pathology causes retinal degeneration, early obesity and type 2 diabetes. Those affected sometimes suffer from kidney failure, deafness or heart problems. The fact that it is linked to both type 2 diabetes and obesity has interested Inserm researchersbecause the two pathologies are linked: 80% of people with obesity suffer from type 2 diabetes. The study of this syndrome has enabled them to determine the role of a protein in the onset of diabetes, and opens the way to new therapies.
The dysfunction of a gene
Alström syndrome is caused by a mutation in the ALMS1 gene, associated with a protein of the same name. In those affected, the gene no longer fulfills its functions and this is what causes the abnormalities of adipose tissue at the origin of type 2 diabetes: the adipocytes, which form this tissue, are no longer able to absorb glucose. “By preventing adipocytes from absorbing glucose, the loss of function of ALMS1 is directly responsible for type 2 diabetes, which makes it a very interesting therapeutic target”explains Vincent Marion, director of research carried out at the medical genetics laboratory of Inserm in Strasbourg.
A clinical trial in early 2021
A test carried out on mice shows that by restoring the functioning of this gene, the tissues can once again assimilate glucose, and it is thus possible to regain glycemic balance, thus treating diabetes. The research team then worked on adipocytes from people with Almström syndrome to understand the mechanisms linked to the ALMS1 gene. They found that it triggers a series of insulin-related molecular reactions. “Thanks to this work on a model of a rare disease, we have discovered a molecule capable on its own of increasing the absorption of glucose by adipocytes and maintaining a good glycemic balance. This makes it a very good therapeutic target to fight type 2 diabetes in general, whether or not associated with obesity”, adds the researcher. He is currently completing tests of this molecule on animals, clinical trials could begin at the beginning of 2021 with diabetic patients.
According to Inserm90% of people with diabetes have type 2 diabetes.
.
