NERVONIC ACID AND DEMYELINATING DISEASE

Demyelination in adrenoleukodystrophy (ALD) is associated with an accu mulation of very long chain saturated fatty acids such as 26:0 stemmin g from a genetic defect in the peroxisomal beta oxidation system respo nsible for the chain shortening of these fatty acids. Long chain monoe noic acids such as erucic acid, 22:1(n-9), can normalise elevated seru m levels of 26:0 in ALD by depressing their biosynthesis from shorter chain saturated fatty acids. Sphingolipids from post mortem ALD brain have decreased levels of nervonic acid, 24:1(n-9), and increased level s of stearic acid, 18:0. Increased levels of 26:0 are accompanied by d ecreased nervonic acid biosynthesis in skin fibroblasts from ALD patie nts. Sphingolipids from post mortem MS brain have the same decreased 2 4:1(n-9) and increased 18:0 seen in post mortem ALD brain. The 24:1(n- 9) content of sphingomyelin is depressed in erythrocytes from multiple sclerosis (MS) patients. Defects in the microsomal biosynthesis of ve ry long chain fatty acids including 24:1(n-9) in 'jumpy' and 'quaking' mice are accompanied by impaired myelination. An impairment in the pr ovision of nervonic acid in demyelinating diseases is indicated, sugge sting that dietary therapy with oils rich in very long chain monenoic acid fatty acids may be beneficial in such conditions.