Hipokampuse ja külgvatsakeste ruumala muutuse uurimine liraglutiidi kroonilise manustamise järel Wolframi sündroomi rotimudelis

Wolframi sündroom (WS) on haruldane autosomaalne retsessiivne haigus, mida põhjustavad mutatsioonid WFS1 geenis. WSi iseloomustavad juveniilne suhkurdiabeet, optilise närvi atroofia, kurtus ja neurodegeneratsioon, mille tõttu surevad patsiendid keskmiselt kolmekümne aasta vanuselt. Neurodegeneratsiooni on WSi puhul vähe uuritud ning seetõttu keskendub käesolev töö WSi rotimudeli hipokampuses ja külgvatsakestes toimuvatele muutustele. WSi rotimudelis suurenesid kuus kuud kestnud katse jooksul nii hipokampuse kui ka külgvatsakeste ruumala. Ajuvatsakeste ruumala suurenemine kaasneb ka teiste neurodegeneratiivsete haigustega ja seega sobiks WSi rotimudelit kasutada ka neurodegeneratiivsete haiguste uurimiseks. Katse käigus ilmnes GLP-1 retseptori agonisti liraglutiidi neuroprotektiivne toime, mistõttu võiks see ravim pidurdada neurodegeneratsiooni ka WSiga patsientide

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

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