Mario Plaas

Update March 5, 2024

Our focus is to discover preclinical Liraglutide and the rest of the GLP1 receptor agonists available on the market to help stop the progression of Wolfram syndrome. Moreover, we are looking into a new generation of GLP1 and GIP co-agonists for the same reason. We are also developing gene therapy against WS-associated neurodegeneration.

University of Tartu, Laboratory Animal Centre

Lifelong treatment with GLP1 receptor agonist in rat model of Wolfram syndrome

Treatment with GLP1 receptor agonists has been shown to normalize ER stress response in several in vitro and in vivo models. Recent research has shown beneficial effect of GLP1 receptor agonist treatment in rat and mouse models of Wolfram syndrome (WS). Early treatment with liraglutide was effective to prevent the development of diabetic phenotype in a rat model of WS. Furthermore, our recent results indicate that 6-month liraglutide treatment reduced neuroinflammation, cellular stress and excitotoxicity in the brainstem of the aged WS rats. Liraglutide treatment also protected retinal ganglion cells from cell death and optic nerve axons from degeneration.

As a WS is a lifelong condition and therefore, any pharmacological treatment of WS patients will also be lifelong. However, the long-lasting nor lifelong effect of such treatment has never been evaluated. Thus, we performed the lifelong experiment to evaluate the safety and efficacy of long-lasting treatment with GLP1 receptor agonist liraglutide in WS rats.

The WS rats were 2 months old at the beginning of the experiment and they were treated for 15 months with liraglutide. The progression of diabetic phenotype, loss of vision, loss of hearing and changes in the brain anatomy were monitored and evaluated during the experiment. Preliminary results are showing that liraglutide treatment delayed the progression of diabetic phenotype, brainstem degeneration, loss of vision and the progression of cataract of WS rat. Now our work is focusing on analyzing all collected data and tissues to make final conclusions of this lifelong liraglutide treatment.

This research was supported by Eye Hope Foundation, grant PUT PSG471 from the Estonian Research Council and by Novo Nordisk who supported us with Liraglutide.

With best regards,
Mario Plaas