Mariana Igoillo-Esteve, PhD, Miriam Cnop, MD PhD

ULB Center for Diabetes Research, Brussels, Belgium

GLP-1 analogs, such as liraglutide, exenatide and dulaglutide among others, are used to treat type 2 diabetes. These drugs are known to promote pancreatic beta cell function and survival, may cross the blood brain barrier, and might have potential beneficial effect on neurons and retinal cells. GLP-1 analogs may therefore be of interest in Wolfram syndrome, to prevent or treat diabetes and potentially neurodegeneration.

In our Center we are studying whether different GLP-1 analogs are beneficial for pancreatic beta cells and neurons in Wolfram syndrome. To answer this question, we are using several preclinical models of Wolfram syndrome including WFS1- knockout mice, WFS1-deficient human beta cells, and induced pluripotent stem cells (iPSC) from people with Wolfram syndrome differentiated into beta cells and cerebellar neurons.

Our preclinical data indicate that GLP-1 analogs prevent and reverse diabetes in Wolfram syndrome mice, and improve the function and survival of WFS1-deficient human beta cells and iPSC-derived beta cells from patients with Wolfram syndrome. The effect of GLP-1 analogs on iPSC-derived neurons is currently under study but our preliminary results suggest that these drugs may help to prevent neuronal demise in Wolfram syndrome. Based on the preliminary data, liraglutide was started (off-label use) in two 9-year-old children with diabetes and Wolfram syndrome. Liraglutide lowered their sugar levels, reduced their glycemic variability, and reduced the amount of insulin needed by 40 to 75%. This improved glycemic control contributed to ameliorate the children’s quality of life and allowed them to switch to carbohydrate-richer diets.

Mariana Igoillo-Esteve, PhD

Miriam Cnop, MD PhD