Fig. 5
From: Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients
Pathogenesis and therapeutic potential of lipids in ALS. In mouse experiments, hyperlipidemia induced by high-energy diets significantly increases the survival rate of ALS G93A mice. Intraventricular infusion of GM3 ganglioside delays the onset of paralysis in SOD1G93A mice. Human metabolomics studies have identified shared lipid pathways in independent ALS cohorts, including significant decreases in certain phosphatidylcholines and lyso-phospholipids, elevated levels of saturated long-chain free fatty acids, β-oxidation-related fatty acid intermediates such as acylcarnitines, and diacylglycerols. Elevated levels of sphingolipids, including sphingomyelins, ceramides, and cholesterol, are observed in the spinal cords of ALS patients and SOD1G93A mice. Specific variants in the SPTLC1 gene lead to loss of ORMDL-mediated inhibitory control over the SPT complex, resulting in unrestricted synthesis of sphingoid bases. Figure created with BioRender.com