Early Intervention and Lifelong Treatment with GLP1 Receptor Agonist Liraglutide in a Wolfram Syndrome Rat Model with an Emphasis on Visual Neurodegeneration, Sensorineural Hearing Loss and Diabetic Phenotype

Cells

Miriam A. Hickey¹  Allen Kaasik¹  Eero Vasar²  Mihkel Plaas³  Marko Pastak⁴  Mario Plaas⁵  Kadri Seppa⁵  Kaia Grete Kukker⁵  Riin Reimets⁵  Anton Terasmaa⁵  Toomas Jagomäe⁵  Lieve Moons⁶  Lies De Groef⁶ 

[1] Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia;Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia;Ear Clinic of Tartu University Hospital, L. Puusepa 1a Street, 50406 Tartu, Estonia;Eye Clinic of Tartu University Hospital, L. Puusepa 8 Street, 50406 Tartu, Estonia;Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia;Research Group Neural Circuit Development and Regeneration, Department of Biology, Belgium & Leuven Brain Institute, University of Leuven, Naamsestraat 61, Box 2464, 3000 Leuven, Belgium;

关键词: wolfram syndrome;    Wfs1;    GLP1 receptor agonist;    liraglutide;    rat model;    neurodegeneration;   

DOI  :  10.3390/cells10113193

来源: DOAJ

【 摘 要 】

Wolfram syndrome (WS), also known as a DIDMOAD (diabetes insipidus, early-onset diabetes mellitus, optic nerve atrophy and deafness) is a rare autosomal disorder caused by mutations in the Wolframin1 (WFS1) gene. Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP1 RA) are effective in delaying and restoring blood glucose control in WS animal models and patients. The GLP1 RA liraglutide has also been shown to have neuroprotective properties in aged WS rats. WS is an early-onset, chronic condition. Therefore, early diagnosis and lifelong pharmacological treatment is the best solution to control disease progression. Hence, the aim of this study was to evaluate the efficacy of the long-term liraglutide treatment on the progression of WS symptoms. For this purpose, 2-month-old WS rats were treated with liraglutide up to the age of 18 months and changes in diabetes markers, visual acuity, and hearing sensitivity were monitored over the course of the treatment period. We found that treatment with liraglutide delayed the onset of diabetes and protected against vision loss in a rat model of WS. Therefore, early diagnosis and prophylactic treatment with the liraglutide may also prove to be a promising treatment option for WS patients by increasing the quality of life.

【 授权许可】

Unknown