Adrenoleukodystrophy (ALD) is an X-linked inherited peroxisomal disorder due to mutations in the ALD protein and characterized by accumulation of very long-chain fatty acids (VLCFA), specifically hexacosanoic acid (C26:0). This can trigger other pathological processes such as mitochondrial dysfunction, oxidative stress, and inflammation, which if involves the brain tissues can result in a lethal form of the disease called childhood cerebral ALD. With the recent addition of ALD to the Recommended Uniform Screening Panel, there is an increase in the number of individuals who are identified with ALD. However, currently, there is no approved treatment for pre-symptomatic individuals that can arrest or delay symptom development. Here, we report our observations investigating nervonic acid, a monounsaturated fatty acid as a potential therapy for ALD. Using ALD patient-derived fibroblasts, we examined whether nervonic acid can reverse VLCFA accumulation similar to erucic acid, the active ingredient in Lorenzo's oil, a dietary intervention believed to alter disease course. We have shown that nervonic acid can reverse total lipid C26:0 accumulation in a concentration-dependent manner in ALD cell lines. Further, we show that nervonic acid can protect ALD fibroblasts from oxidative insults, presumably by increasing intracellular ATP production. Thus, nervonic acid can be a potential therapeutic for individuals with ALD, which can alter cellular biochemistry and improve its function.
Keywords: Adrenoleukodystrophy; Dietary lipids; Fibroblasts; Monounsaturated fatty acids; Peroxisomes; Sphingomyelin; Very long-chain fatty acids.
© 2022. The American Society for Experimental NeuroTherapeutics, Inc.