A Two-Year Trial of Oleic and Erucic Acids (“Lorenzo's Oil”) as Treatment for Adrenomyeloneuropathy

Aubourg, Patrick; Adamsbaum, C.; Mc, Lavallard-Rousseau; Rocchiccioli, F.; Cartier, Nathalie; Jambaqué, Isabelle; Jakobezak, C; Lemaître, Anne-Laure; Boureau, F; Wolf, Christian

doi:10.1056/nejm199309093291101

Cited by 215 publications

(90 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…24 In recent years, several therapeutic approaches have been proposed for this disease, but their effectiveness is still a matter of debate. 2,3,14,25 Therefore, the assessment of this disease is very important in order to monitor the efficacy of treatment. Magnetic resonance imaging (MRI) usually reveals typical brain lesions in children; 16 a high percentage of brain MRI abnormalities has been found in AMN, 4 but many of the patients were in advanced stages of the disease and presented predominant signs of mental deterioration.…”

mentioning

confidence: 99%

Abnormalities of somatosensory and motor evoked potentials in adrenomyeloneuropathy: Comparison with magnetic resonance imaging and clinical findings

et al. 1997

View full text Add to dashboard Cite

mentioning

confidence: 99%

Abnormalities of somatosensory and motor evoked potentials in adrenomyeloneuropathy: Comparison with magnetic resonance imaging and clinical findings

et al. 1997

View full text Add to dashboard Cite

“…Various therapeutic approaches including a lipid diet combining the administration of glycerol trioleate and trierucate (Lorenzo's oil) (14)(15)(16) failed to modify the evolution of the cerebral lesions of ALD. Four years ago, we reported that bone marrow transplantation (BMT) can reverse demyelination, if performed at a relatively early stage of its development (17).…”

mentioning

confidence: 99%

Retroviral-mediated gene transfer corrects very-long-chain fatty acid metabolism in adrenoleukodystrophy fibroblasts.

Cartier

Lopez

Moullier

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Adrenoleukodystrophy (ALD), a lethal demyelinating disease of the brain, is caused by mutations of a gene encoding an ATP-binding transporter, called ALDP, localized in the peroxisomal membrane. It is associated with a defective oxidation of very-long-chain fatty acids, leading to their accumulation in many tissues. This study reports that the retroviral-mediated transfer of the ALD cDNA restored very-long-chain fatty acid oxidation in ALD fibroblasts in vitro following abundant expression and appropriate targeting of the vector-encoded ALDP in peroxisomes. The same method may be used in hematopoietic cells as a further step of a gene therapy approach of ALD.X chromosome-linked adrenoleukodystrophy (ALD) is a devastating neurologic disorder that affects 1/15,000 males with different clinical phenotypes within the same kindred. The cerebral lesions occur in young boys between the age of 5 and 12 years and are characterized by progressive demyelination leading to rapid deterioration and death within 3-5 years of diagnosis (1).The main biochemical defect of ALD is an impaired oxidation of saturated very-long-chain fatty acids (VLCFAs) and their accumulation in cerebral white matter, adrenal glands, fibroblasts, and plasma (1, 2). In ALD fibroblasts, VLCFAs are normally transported across the peroxisomal membrane (3), but a functional defect of VLCFA-CoA synthetase impairs their (3-oxidation (4-6).The recent cloning and demonstration of deletions and mutations of theALD gene (7-10) revealed that the metabolic abnormality is due to defects of a 75-kDa peroxisomal integral membrane protein (11), a member of the ATP-binding cassette (ABC) transporter family (12). The function of ALD protein (ALDP) is unknown, but it is necessary for the activity of the VLCFA-CoA synthetase, also localized in the peroxisomal membrane (13).Various therapeutic approaches including a lipid diet combining the administration of glycerol trioleate and trierucate (Lorenzo's oil) (14-16) failed to modify the evolution of the cerebral lesions of ALD. Four years ago, we reported that bone marrow transplantation (BMT) can reverse demyelination, if performed at a relatively early stage of its development (17). Since allogenic BMT is often limited by the lack of histocompatible donors and has serious secondary effects, we considered transplantation of the patient's own bone marrow cells after transfer of the normal ALD gene as an alternative strategy.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. Fig. 1A), a 2.43-kb Spe I-EcoRI fragment was isolated from the fulllength human ALDP cDNA, Bcl I linkered, and inserted in the sense orientation into the unique BamHI restriction site of the M48 retroviral vector, a Moloney-based retroviral vector (19). In this M48-ALD construct, expression of ALD cDNA is under the control of the mouse phosphoglycerate kinase (PGK) gene promoter.The GLU-3...

show abstract

“…It is known that a ketogenic diet acts to increase the VLCFA levels, while lowering the intake of fatty acids lowers their level (e.g. the use of Lorentzo oil in X-ALD) [1,15,18].…”

Section: Discussionmentioning

confidence: 99%

Very long-chain fatty acids in Rett syndrome

Stradomska

Tylki‐Szymańska

Bentkowski

1999

European Journal of Pediatrics

View full text Add to dashboard Cite

show abstract

A Two-Year Trial of Oleic and Erucic Acids (“Lorenzo's Oil”) as Treatment for Adrenomyeloneuropathy

Abstract: In this open trial we found no evidence of a clinically relevant benefit from dietary treatment with oleic and erucic acids ("Lorenzo's oil") in patients with adrenomyeloneuropathy.

Cited by 215 publications

References 42 publications

Abnormalities of somatosensory and motor evoked potentials in adrenomyeloneuropathy: Comparison with magnetic resonance imaging and clinical findings

Abnormalities of somatosensory and motor evoked potentials in adrenomyeloneuropathy: Comparison with magnetic resonance imaging and clinical findings

Retroviral-mediated gene transfer corrects very-long-chain fatty acid metabolism in adrenoleukodystrophy fibroblasts.

Very long-chain fatty acids in Rett syndrome

Contact Info

Product

Resources

About