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
Toomas Jagomäe,
Kadri Seppa,
Riin Reimets,
Marko Pastak,
Mihkel Plaas,
Miriam A. Hickey,
Kaia Grete Kukker,
Lieve Moons,
Lies De Groef,
Eero Vasar,
Allen Kaasik,
Anton Terasmaa,
Mario Plaas
Affiliations
Toomas Jagomäe
Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia
Kadri Seppa
Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia
Riin Reimets
Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia
Marko Pastak
Eye Clinic of Tartu University Hospital, L. Puusepa 8 Street, 50406 Tartu, Estonia
Mihkel Plaas
Ear Clinic of Tartu University Hospital, L. Puusepa 1a Street, 50406 Tartu, Estonia
Miriam A. Hickey
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia
Kaia Grete Kukker
Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia
Lieve Moons
Research Group Neural Circuit Development and Regeneration, Department of Biology, Belgium & Leuven Brain Institute, University of Leuven, Naamsestraat 61, Box 2464, 3000 Leuven, Belgium
Lies De Groef
Research Group Neural Circuit Development and Regeneration, Department of Biology, Belgium & Leuven Brain Institute, University of Leuven, Naamsestraat 61, Box 2464, 3000 Leuven, Belgium
Eero Vasar
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia
Allen Kaasik
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia
Anton Terasmaa
Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia
Mario Plaas
Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia
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.
