Journal of Molecular Neuroscience

, Volume 33, Issue 1, pp 105–113 | Cite as

“Lorenzo’s Oil” Therapy for X-linked Adrenoleukodystrophy: Rationale and Current Assessment of Efficacy

  • Hugo W. Moser
  • Ann B. MoserEmail author
  • Kim Hollandsworth
  • N. Hong Brereton
  • Gerald V. Raymond


X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder that damages the nervous system and is associated with the accumulation of saturated very long chain fatty acids (SVLCFA). Oral administration of “Lorenzo’s oil” (LO), a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, normalizes the SVLCFA levels in plasma, but its clinical efficacy and the clinical indications for its use have been controversial for more than 15 years. We review the biochemical effects of LO administration and the rationale for its use and present a current appraisal of its capacity to reduce the risk for the childhood cerebral phenotype when administered to asymptomatic boys and to slow progression of adrenomyeloneuropathy in patients without cerebral involvement. We also present current efforts to provide definitive evaluation of its clinical efficacy and discuss its possible role in the new therapeutic opportunities that will arise if newborn screening for X-ALD is validated and implemented.


Adrenoleukodystrophy Therapy Lorenzo’s oil Glyceryl trioleate Glyceryl trierucate Fatty acids Erucic acid Very long chain fatty acids Clinical trials Newborn screening 


  1. Abdellatif, A. M. (1972). Cardiopathogenic effects of dietary rapeseed oil. Nutrition Reviews, 30, 2–6.PubMedCrossRefGoogle Scholar
  2. Asheuer, M., Bieche, I., Laurendeau, I., Moser, A., Hainque, B., Vidaud, M., et al. (2005). Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy. Human Molecular Genetics, 14, 1293–1303.PubMedCrossRefGoogle Scholar
  3. Assies, J., van Geel, B., Weverling, G. J., Haverkort, E. B., & Barth, P. G. (1994). Endocrine evaluation during dietary therapy for adrenomyeloneuropathy. In H. R. Bhatt, G. H. T. James, G. M. Besser, G. F. Bottazzo, & H. E. Keen (Eds.), Advances in Thomas Addison’s diseases (pp. 191–198). Bristol: Journal of Endocrinology.Google Scholar
  4. Aubourg, P., Adamsbaum, C., Lavallard-Rousseau, M. C., Rocchiccioli, F., Cartier, N., Jambaque, I., et al. (1993). A two-year trial of oleic and erucic acids (“Lorenzo’s oil”) as treatment for adrenomyeloneuropathy. New England Journal of Medicine, 329, 745–752.PubMedCrossRefGoogle Scholar
  5. Aubourg, P., Blanche, S., Jambaque, I., Rocchiccioli, F., Kalifa, G., Naud-Saudreau, C., et al. (1990). Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation. New England Journal of Medicine, 322, 1860–1866.PubMedCrossRefGoogle Scholar
  6. Bezman, L., & Moser, H. W. (1998). Incidence of X-linked adrenoleukodystrophy and the relative frequency of its phenotypes. American Journal of Medical Genetics, 76, 415–419.PubMedCrossRefGoogle Scholar
  7. Bezman, L., Moser, A. B., Raymond, G. V., Rinaldo, P., Watkins, P. A., Smith, K. D., et al. (2001). Adrenoleukodystrophy: Incidence, new mutation rate, and results of extended family screening. Annals of Neurology, 49, 512–517.PubMedCrossRefGoogle Scholar
  8. Bizzozero, O. A., Zuniga, G., & Lees, M. B. (1991). Fatty acid composition of human myelin proteolipid protein in peroxisomal disorders. Journal of Neurochemistry, 56, 872–878.PubMedCrossRefGoogle Scholar
  9. Boehm, C. D., Cutting, G. R., Lachtermacher, M. B., Moser, H. W., & Chong, S. S. (1999). Accurate DNA-based diagnostic and carrier testing for X-linked adrenoleukodystrophy. Molecular Genetics and Metabolism, 66, 128–136.PubMedCrossRefGoogle Scholar
  10. Bourre, J. M., Daudu, O., & Baumann, N. (1976). Nervonic acid biosynthesis by erucyl-CoA elongation in normal and quaking mouse brain microsomes. Elongation of other unsaturated fatty acyl-CoAs (mono and poly-unsaturated). Biochimica Et Biophysica Acta, 424, 1–7.PubMedGoogle Scholar
  11. Brown, F. R. 3rd, Van Duyn, M. A., Moser, A. B., Schulman, J. D., Rizzo, W. B., Snyder R. D., et al. (1982). Adrenoleukodystrophy: Effects of dietary restriction of very long chain fatty acids and of administration of carnitine and clofibrate on clinical status and plasma fatty acids. Johns Hopkins Medical Journal, 151, 164–172.PubMedGoogle Scholar
  12. Choi, J. K., Ho J., Curry, S., Qin, D., Bittman, R., & Hamilton, J. A. (2002). Interactions of very long-chain saturated fatty acids with serum albumin. Journal of Lipid Research, 43, 1000–1010.PubMedCrossRefGoogle Scholar
  13. Cox, C., Dubey P., Raymond, G. V., Mahmood, A., Moser, A. B., & Moser, H. W. (2006). Cognitive evaluation of neurologically asymptomatic boys with X-linked adrenoleukodystrophy. Archives of Neurology, 63, 69–73.PubMedCrossRefGoogle Scholar
  14. Dean, M., Hamon, Y., & Chimini, G. (2001). The human ATP-binding cassette (ABC) transporter superfamily. Journal of Lipid Research, 42, 1007–1017.PubMedGoogle Scholar
  15. Di Biase, A., Di Benedetto, R., Fiorentini, C., Travaglione, S., Salvati, S., Attorri, L., et al. (2004). Free radical release in C6 glial cells enriched in hexacosanoic acid: Implication for X-linked adrenoleukodystrophy pathogenesis. Neurochemistry International, 44, 215–221.PubMedCrossRefGoogle Scholar
  16. Dubey, P., Raymond, G., Moser, A. B., Kharkar, S., Bezman, L., & Moser, H. W. (2005). Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long chain fatty acid screening. Journal de Pediatria, 146, 528–532.CrossRefGoogle Scholar
  17. Dubois-Dalcq, M., Feigenbaum, V., & Aubourg, P. (1999). The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal disorder. Trends in Neurosciences, 22, 4–12.PubMedCrossRefGoogle Scholar
  18. Fatemi, A., Smith, S. A., Dubey, P., Zackowski, K. M., Bastian, A. J., van Zijl, P. C., et al. (2005). Magnetization transfer MRI demonstrates spinal cord pathology in adrenomyeloneuropathy. Neurology, 64, 1739–1745.PubMedCrossRefGoogle Scholar
  19. Feigenbaum, V., Gelot, A., Casanova, P., Daumas-Duport, C., Aubourg, P., & Dubois-Dalcq, M. (2000). Apoptosis in the central nervous system of cerebral adrenoleukodystrophy patients. Neurobiology of Disease, 7, 600–612.PubMedCrossRefGoogle Scholar
  20. Gilg, A. G., Singh, A. K., & Singh, I. (2000). Inducible nitric oxide synthase in the central nervous system of patients with X-adrenoleukodystrophy. Journal of Neuropathology and Experimental Neurology, 59, 1063–1069.PubMedGoogle Scholar
  21. Golovko, M. Y., & Murphy, E. J. (2006). Uptake and metabolism of plasma derived erucic acid by rat brain. Journal of Lipid Research, 47, 1289–1297.PubMedCrossRefGoogle Scholar
  22. Hamilton, J. A., Era, S., Bhamidipati, S. P., & Reed, R. G. (1991). Locations of the three primary binding sites for long-chain fatty acids on bovine serum albumin. Proceedings of the National Academy of Sciences of the United States of America, 88, 2051–2054.PubMedCrossRefGoogle Scholar
  23. Ho, J. K., Moser, H., Kishimoto, Y., & Hamilton, J. A. (1995). Interactions of a very long chain fatty acid with model membranes and serum albumin. Implications for the pathogenesis of adrenoleukodystrophy. Journal of Clinical Investigation, 96, 1455–1463.PubMedGoogle Scholar
  24. Hubbard, W. C., Moser, A. B., Tortorelli, S., Liu, A., Jones, D., & Moser, H. W. (2006). Combined liquid chromatography-Tandem mass spectrometry as an analytical method for high throughput screening for X-linked adrenoleukodystrophy and other peroxisomal disorders: Preliminary findings. Molecular Genetics and Metabolism, 89, 185-187.PubMedCrossRefGoogle Scholar
  25. Igarashi, M., Belchis, D., & Suzuki, K. (1976a). Brain gangliosides in adrenoleukodystrophy. Journal of Neurochemistry, 27, 327–328.CrossRefGoogle Scholar
  26. Igarashi, M., Schaumburg, H. H., Powers, J., Kishmoto, Y., Kolodny, E., & Suzuki, K. (1976b). Fatty acid abnormality in adrenoleukodystrophy. Journal of Neurochemistry, 26, 851–860.PubMedCrossRefGoogle Scholar
  27. Ito, M., Blumberg, B. M., Mock, D. J., Goodman, A. D., Moser, A. B., Moser, H. W., et al. (2001). Potential environmental and host participants in the early white matter lesion of adreno-leukodystrophy: Morphologic evidence for CD8 cytotoxic T cells, cytolysis of oligodendrocytes, and CD1-mediated lipid antigen presentation. Journal of Neuropathology and Experimental Neurology, 60, 1004–1019.PubMedGoogle Scholar
  28. Kemp, S., Valianpour, F., Denis, S., Ofman, R., Sanders, R. J., Mooyer, P., et al. (2005). Elongation of very long-chain fatty acids is enhanced in X-linked adrenoleukodystrophy. Molecular Genetics and Metabolism, 84, 144–151.PubMedCrossRefGoogle Scholar
  29. Kickler, T. S., Zinkham, W. H., Moser, A., Shankroff, J., Borel, J., & Moser, H. (1996). Effect of erucic acid on platelets in patients with adrenoleukodystrophy. Biochemical and Molecular Medicine, 57, 125–133.PubMedCrossRefGoogle Scholar
  30. Knazek, R. A., Rizzo, W. B., Schulman, J. D., & Dave, J. R. (1983). Membrane microviscosity is increased in the erythrocytes of patients with adrenoleukodystrophy and adrenomyeloneuropathy. Journal of Clinical Investigation, 72, 245–248.PubMedGoogle Scholar
  31. Koehler, W., & Sokolowski, P. (1999). A new disease-specific scoring system for adult phenotypes of X-linked adrenoleukodystrophy. Journal of Molecular Neuroscience, 13, 247–252.CrossRefGoogle Scholar
  32. Koehler, W., & Sokolowski, P. (2005). Clinical phenotypes, diagnosis and treatment of adulthood X-linked adrenoleukodystrophy. In J. Berger, S. Stoeckler & W. Koehler (Eds.), Understanding and treating adrenoleukodystrophy: Present state and future perspectives (pp. 28–60). SPS Verlagsgeseltschaft: Verlag Heilbronn.Google Scholar
  33. Kurtzke, J. F. (1983). Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology, 33, 1444–1452.PubMedGoogle Scholar
  34. Moser, H. W., Aubourg P., Cornblath, D., Borel, J., Wu, Y.-W., Bergin, A., et al. (1991). Therapy for X-linked adrenoleukodystrophy. In R. J. Desnick (Ed.), Treatment of genetic disease (pp. 111–129). New York: Churchill Livingstone.Google Scholar
  35. Moser, H. W., & Brereton, N. H. (2005) Adrenoleukodystrophy and other peroxisomal disorders. In S. W. Ekvall & V. K. Ekvall (Eds.), Pediatric nutrition in chronic diseases and developmental disorders: Prevention, assessment and treatment (pp. 312–317). New York: Oxford Univ. Press.Google Scholar
  36. Moser, A. B., Jones, D. S., Raymond, G. V., & Moser, H. W. (1999a). Plasma and red blood cell fatty acids in peroxisomal disorders. Neurochemical Research, 24, 187–197.PubMedCrossRefGoogle Scholar
  37. Moser, A. B., Kreiter, N., Bezman, L., Lu, S., Raymond, G. V., Naidu, S., et al. (1999b). Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls. Annals of Neurology, 45, 100–110.PubMedCrossRefGoogle Scholar
  38. Moser, A. B., & Moser, H. W. (1999). The prenatal diagnosis of X-linked adrenoleukodystrophy. Prenatal Diagnosis, 19, 46–48.PubMedCrossRefGoogle Scholar
  39. Moser, H. W., Moser, A. B., Kawamura, N., Murphy, J., Suzuki, K., Schaumburg, H., et al. (1980). Adrenoleukodystrophy: Elevated C26 fatty acid in cultured skin fibroblasts. Annals of Neurology, 7, 542–549.PubMedCrossRefGoogle Scholar
  40. Moser, H. W., Raymond, G. V., & Dubey, P. (2005). Adrenoleukodystrophy: New approaches to a neurodegenerative disease. JAMA, 294, 3131–3134.PubMedCrossRefGoogle Scholar
  41. Moser, H. W., Raymond, G. V., Koehler, W., Sokolowski, P., Hanefeld, F., Korenke, G. C., et al. (2003). Evaluation of the preventive effect of glyceryl trioleate–trierucate (“Lorenzo’s oil”) therapy in X-linked adrenoleukodystrophy: Results of two concurrent trials. Advances in Experimental Medicine and Biology, 544, 369–387.PubMedGoogle Scholar
  42. Moser, H. W., Raymond, G. V., Lu, S. E., Muenz, L. R., Moser, A. B., Xu, J., et al. (2005). Follow-up of 89 Lorenzo’s oil treated asymptomatic adrenoleukodystrophy patients. Archives of Neurology, 62, 1073–1080.PubMedCrossRefGoogle Scholar
  43. Mosser, J., Douar, A. M., Sarde, C. O., Kioschis, P., Feil, R., Moser, H., et al. (1993). Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature, 361, 726–730.PubMedCrossRefGoogle Scholar
  44. Odone, A., & Odone, M. (1989) Lorenzo’s oil: A new treatment for adrenoleukodystrophy. Journal of Pediatric Neuroscience, 5, 55–61.Google Scholar
  45. Oya, Y., Nakayasu, H., Fujita, N., Suzuki, K., & Suzuki, K. (1998). Pathological study of mice with total deficiency of sphingolipid activator proteins (SAP knockout mice). Acta Neuropathologica (Berl.), 96, 29–40.CrossRefGoogle Scholar
  46. Oz, G., Tkac, I., Charnas, L. R., Choi, I. Y., Bjoraker, K. J., Shapiro, E. G., et al. (2005). Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients. Neurology, 64, 434–441.PubMedGoogle Scholar
  47. Paintlia, A. S., Gilg, A. G., Khan, M., Singh, A. K., Barbosa, E., & Singh I. (2003) Correlation of very long chain fatty acids accumulation and inflammatory disease progression in childhood ALD: Implications for potential therapies. Neurobiology of Disease, 14, 425–439.PubMedCrossRefGoogle Scholar
  48. Peters, C., Charnas, L. R., Tan, Y., Ziegler, R. S., Shapiro, E. G., DeFor, T., et al. (2004). Cerebral X-linked adrenoleukodystrophy: The international hematopoietic cell transplantation experience from 1982 to 1999. Blood, 104, 881–888.PubMedCrossRefGoogle Scholar
  49. Poulos, A., Gibson, R., Sharp, P., Beckman, K., & Grattan-Smith, P. (1994). Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo’s oil. Annals of Neurology, 36, 741–746.PubMedCrossRefGoogle Scholar
  50. Powers, J. M., DeCiero, D. P., Cox, C., Richfield, E. K., Ito, M., Moser, A. B., et al. (2001). The dorsal root ganglia in adrenomyeloneuropathy: Neuronal atrophy and abnormal mitochondria. Journal of Neuropathology and Experimental Neurology, 60, 493–501.PubMedGoogle Scholar
  51. Powers, J. M., DeCiero, D. P., Ito, M., Moser, A. B., & Moser, H. W. (2000). Adrenomyeloneuropathy: A neuropathologic review featuring its noninflammatory myelopathy. Journal of Neuropathology and Experimental Neurology, 59, 89–102.PubMedGoogle Scholar
  52. Powers, J. M., Liu, Y., Moser, A. B., & Moser, H. W. (1992). The inflammatory myelinopathy of adreno-leukodystrophy: Cells, effector molecules, and pathogenetic implications. Journal of Neuropathology and Experimental Neurology 51, 630–643.PubMedGoogle Scholar
  53. Powers, J. M., Pei, Z., Heinzer, A. K., Deering, R., Moser, A. B., Moser, H. W., et al. (2005). Adrenoleukodystrophy: Oxidative stress of mice and men. Journal of Neuropathology and Experimental Neurology 64, 1067–1079.PubMedGoogle Scholar
  54. Powers, J. M., Schaumburg, H. H., Johnson, A. B., & Raine, C. S. (1980). A correlative study of the adrenal cortex in adreno-leukodystrophy—evidence for a fatal intoxication with very long chain saturated fatty acids. Investigative & Cell Pathology, 3, 353–376.Google Scholar
  55. Rasmussen, M., Moser, A. B., Borel, J., Khangoora, S., & Moser, H. W. (1994). Brain, liver, and adipose tissue erucic and very long chain fatty acid levels in adrenoleukodystrophy patients treated with glyceryl trierucate and trioleate oils (Lorenzo’s oil). Neurochemical Research, 19, 1073–1082.PubMedCrossRefGoogle Scholar
  56. Rizzo, W. B., Leshner, R. T., Odone, A., Craft, D. A., Jennings, S. S., & Jaitly, R. (1990). X-linked adrenoleukodystrophy: Biochemical and clinical efficacy of dietary erucic acid therapy. In G. Uziel, R. J. A. Wanders, & M. E. Cappa (Eds.), Adrenoleukodystrophy and other peroxisomal disorders (pp. 149–162). Amsterdam: Excerpta Medica.Google Scholar
  57. Rizzo, W. B., Leshner, R. T., Odone, A., Dammann, A. L., Craft, D. A., Jensen, M. E., et al. (1989). Dietary erucic acid therapy for X-linked adrenoleukodystrophy. Neurology, 39, 1415–1422.PubMedGoogle Scholar
  58. Rizzo, W. B., Phillips, M. W., Dammann, A. L., Leshner, R. T., Jennings, S. S., Avigan J., et al. (1987). Adrenoleukodystrophy: Dietary oleic acid lowers hexacosanoate levels. Annals of Neurology, 21, 232–239.PubMedCrossRefGoogle Scholar
  59. Rizzo, W. B., Watkins, P. A., Phillips, M. W., Cranin, D., Campbell, B., & Avigan, J. (1986). Adrenoleukodystrophy: Oleic acid lowers fibroblast saturated C22-26 fatty acids. Neurology, 36, 357–361.PubMedGoogle Scholar
  60. Sauer, F. D., & Kramer, J. K. G. (1983). The Problems Associated with the Feeding of High Erucic Acid Rapeseed Oils and Some Fish Oils to Experimental Animals. In J. K. G. Kramer, F. D. Sauer, & W. J. Pigden (Eds.), High and low erucic acid rapeseed oils (pp. 253–292). Toronto: Academic Press.Google Scholar
  61. Schaumburg, H. H., Powers, J. M., Raine, C. S., Suzuki, K., & Richardson, E. P. Jr. (1975). Adrenoleukodystrophy. A clinical and pathological study of 17 cases. Archives of Neurology, 32, 577–591.PubMedGoogle Scholar
  62. Shapiro, E., Krivit, W., Lockman, L., Jambaque, I., Peters, C., Cowan, M., et al. (2000). Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet, 356, 713–718.PubMedCrossRefGoogle Scholar
  63. Tagawa, Y., Laroy, W., Nimrichter, L., Fromholt, S. E., Moser, A. B., Moser, H. W., et al. (2002). Anti-ganglioside antibodies bind with enhanced affinity to gangliosides containing very long chain fatty acids. Neurochemical Research, 27, 847–855.PubMedCrossRefGoogle Scholar
  64. Tsuji, S., Suzuki, M., Ariga, T., Sekine, M., Kuriyama, M., & Miyatake, T. (1981). Abnormality of long-chain fatty acids in erythrocyte membrane sphingomyelin from patients with adrenoleukodystrophy. Journal of Neurochemistry, 36, 1046–1049.PubMedCrossRefGoogle Scholar
  65. Uziel, G., Bertini, E., Bardelli, P., Rimoldi, M., & Gambetti, M. (1991). Experience on therapy of adrenoleukodystrophy and adrenomyeloneuropathy. Developmental Neuroscience, 13, 274–279.PubMedGoogle Scholar
  66. Valianpour, F., Selhorst, J. J. M., van Lint, L. E. M., van Gennip, A. H., Wanders, R. J. A., & Kemp, S. (2003). Analysis of very long chain fatty acids using electrospray ionization mass spectrometry. Molecular Genetics and Metabolism, 79, 189–196.PubMedCrossRefGoogle Scholar
  67. van Geel, B. M., Assies, J., Haverkort, E. B., Koelman, J. H., Verbeeten, B. Jr., Wanders R. J., et al. (1999). Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with “Lorenzo’s oil”. Journal of Neurology, Neurosurgery and Psychiatry, 67, 290–299.CrossRefGoogle Scholar
  68. Vargas, C. R., Wajner, M., Sirtori, L. R., Goulart, L., Chiochetta, M., Coelho, D., et al. (2004). Evidence that oxidative stress is increased in patients with X-linked adrenoleukodystrophy. Biochimica et Biophysica Acta, 1688, 26–32.PubMedGoogle Scholar
  69. Whitcomb, R. W., Linehan, W. M., & Knazek, R. A. (1988). Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. Journal of Clinical Investigation, 81, 185–188.PubMedCrossRefGoogle Scholar
  70. Zackowski, K., Dubey, P., Raymond, G. V., Mahmood, A., Moser, A. B., & Moser, H. W. (2006). Relating sensorimotor function and axonal integrity in adrenomyeloneuropathy. Archives of Neurology, 63, 74–80.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Hugo W. Moser
    • 1
  • Ann B. Moser
    • 1
    Email author
  • Kim Hollandsworth
    • 1
  • N. Hong Brereton
    • 2
  • Gerald V. Raymond
    • 1
  1. 1.Department of NeurogeneticsKennedy Krieger InstituteBaltimoreUSA
  2. 2.Department of NutritionJohns Hopkins HospitalBaltimoreUSA

Personalised recommendations