Talarozole Improves Key Features Of Leigh Syndrome - Talarozole is a promising drug candidate for Leigh Syndrome

Leigh Syndrome is progressing rare disease leading to neurodegenerative processes starting in early childhood. The disease is incurable and usually leads to death in early childhood. The invention discloses the azole compound talarozole as a promising drug candidate for the treamtent of Leigh disease. The inventors could demonstrate that talarozole rescued neuronal morphogenesis in Leigh neurons, lowered lactate release and improved growth rate in Leigh midbrain organoids. Mechanistically, talarozole modulated the retinoic acid pathway and membrane-associate lipid metabolism. Hence talarozole seems to be a promising first-in-class candidate for the treatment of Leigh Syndrome by rescuing defect energy metabolism.

As shown in Figure 1:

(A) Midbrain organoids (MO) from Leigh syndrome patients express low level dopaminergic marker tyrosine hydroxylase (TH) and dysregulated pattern of expression of dendritic marker MAP2. Treatment with Talarozole (Tal) corrects these defects.

(B) The pathological increase of lactate produced by Leigh midbrain organoids is reduced following treatment with Talarozole (Tal).

(C) The functionality of Leigh midbrain organoids is significantly improved following treatment with Talarozole (Tal).