New Grant to Advance Wolfram Syndrome Research

New Grant to Advance Wolfram Syndrome Research at the University of Tartu

A five-year research project titled “A New Frontier in Wolfram Syndrome Research: Unraveling Pathophysiology and Pioneering Targeted Therapies” will run from 1 January 2026 to 31 December 2030, led by Mario Plaas at the University of Tartu (Faculty of Medicine, Institute of Biomedicine and Translational Medicine). The project is funded by the Estonian Research Council through a personal research grant, awarded to Plaas, with the funding period beginning in 2026 and lasting five years (total budget 1,35M EUR).

Wolfram syndrome 1 (WS) is a rare genetic disorder for which no effective treatment is currently available. The condition is typically characterised by early-onset diabetes, progressive loss of vision and hearing, and neurodegeneration—placing a heavy burden on patients and families and underscoring the urgent need for new therapeutic options.

The research team will investigate a central hypothesis: that an imbalance between excitatory and inhibitory neurotransmission, together with dysregulated autophagy, contributes to the rapid progression of Wolfram syndrome symptoms. By clarifying these mechanisms, the project aims to open new avenues for targeted therapies.

To test this approach, the study will use a transgenic rat model of Wolfram syndrome to evaluate drug regimens designed to address GABAergic vulnerability and autophagy-related dysfunction, including combination strategies that incorporate incretin analogs. These approaches are of particular interest because they may also support healthy ageing, potentially linking insights from Wolfram syndrome to broader questions in neurodegenerative and metabolic disease.

By combining advanced disease models with mechanistic and therapeutic testing, the project seeks to both deepen understanding of Wolfram syndrome biology and identify promising directions for future treatment development.