Leigh syndrome
https://pmc.ncbi.nlm.nih.gov/articles/PMC12907114
Leigh syndrome is a severe childhood brain disorder caused by faulty mitochondria, the parts of cells that produce energy. When the brain cannot make enough energy, children can develop brain lesions, movement problems, and life-threatening complications. One common cause is a defect in Complex I, a key step in the energy-producing process. There are currently no treatments that slow or stop the disease. This study tested a new experimental drug called NV354, designed to help the brain make energy even when Complex I is not working. NV354 is a “prodrug” of succinate, meaning it turns into succinate inside the body. Succinate is a natural molecule that allows mitochondria to produce energy through a different pathway, bypassing the defective Complex I. Researchers used a mouse model of Leigh syndrome that develops brain damage and movement problems like those seen in children. Mice treated with NV354 early in life developed fewer brain lesions, especially in areas normally hit hardest by the disease. They also showed better movement and survived longer before symptoms worsened. The drug successfully delivered succinate into the brain, improved energy production, reduced inflammation, and prevented cell death. NV354 caused no major side effects, suggesting it may be safe for future human testing. These results show strong potential for NV354 as a future treatment for Leigh Syndrome.