Frontiers in Endocrinology · 9 authors, 5 centres
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This preclinical study in a rat model of Wolfram Syndrome found that long-term treatment with the dual-incretin agonist DA-CH5, started after symptom onset, reversed glucose intolerance and protected against visual acuity loss and retinal cell density decline, but did not rescue hearing loss.
Eight-month-old Wfs1 knock-out and wild-type rats were treated with the dual-incretin agonist DA-CH5 or saline for four months to evaluate therapeutic effects in a Wolfram Syndrome model. DA-CH5 therapy reversed glucose intolerance and provided lasting anti-diabetogenic protection in KO rats. Treatment also normalized pancreatic mass and increased endocrine islet area and β-cell density, indicating regenerative potential. DA-CH5 treatment improved visual acuity and preserved retinal ganglion cell density, although hearing loss was not rescued. The study demonstrates pleiotropic effects of long-term dual incretin agonism, including reversal of disease progression when treatment began after symptom onset, suggesting a promising therapeutic avenue for Wolfram Syndrome.
