Evaluation of the Preventive Effect of Glyceryl Trioleate-Trierucate (“Lorenzo’s Oil”) Therapy in X-Linked Adrenoleukodystrophy: Results of Two Concurrent Trials

Moser, Hugo W.; Raymond, Gerald V.; Köehler, Wolfgang; Sokolowski, Piotr; Hanefeld, F.; Korenke, Georg Christoph; Green, Anne; Loes, D. J.; Hunneman, D. H.; Jones, Richard O.; Lu, Shou En; Uziel, Graziella; Girós, M.; Roels, Frank

doi:10.1007/978-1-4419-9072-3_47

Cited by 55 publications

(53 citation statements)

References 27 publications

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“…Here, we demonstrate for the first time that [14-14 C]22:1n-9 is taken up by the brain and esterified into brain lipid compartments. Direct infusion of C]22:1n-9 alters the targeting, with more tracer found esterified in the phospholipid pools, suggesting that prolonged brain exposure alters the targeting of this fatty acid, consistent with the study demonstrating that early treatment with LO is clinically beneficial (42)(43)(44). In either infusion paradigm, brain [14- …”

supporting

confidence: 81%

“…The lack of increased 22:1n-9 in brains from treated X-ALD patients suggests limited uptake into the central nervous system, perhaps as a result of poor movement of 22: 1n-9 across the blood-brain barrier (BBB). A recent trial contradicts the supposition that LO is not effective, as it demonstrates that LO reduces clinical symptoms of X-ALD when administered early in life (42)(43)(44). This suggests that prolonged exposure to LO is clinically beneficial, although this clinical trial does not indicate that 22:1n-9 crosses the BBB; rather, it suggests that 22:1n-9 in the diet is beneficial in reducing 26:0 in the plasma.…”

mentioning

confidence: 78%

“…Recent studies demonstrate that the use of LO in patients is effective (42,43), but only in patients without neurological involvement (64). In patients with neurological symptoms, bone marrow transplantation has proven to be successful (1).…”

Section: Discussionmentioning

confidence: 99%

“…LO dietary therapy has demonstrated in a number of clinical trials efficacy in ameliorating peripheral VLCFA levels associated with X-ALD and now demonstrates strong potential in limiting central nervous system demyelination (42)(43)(44). Yet, the question regarding the uptake of 22:1n-9 in the brain and its subsequent metabolism and deposition into brain lipid compartments remains unanswered.…”

mentioning

confidence: 99%

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Uptake and metabolism of plasma-derived erucic acid by rat brain

Golovko

Murphy

2006

Journal of Lipid Research

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confidence: 81%

mentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Uptake and metabolism of plasma-derived erucic acid by rat brain

Golovko

Murphy

2006

Journal of Lipid Research

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“…Recent reports from two independent concurrent treatment trials both demonstrated a preventive effect of LO on disease onset in asymptomatic boys with previously normal brain MRI [13,81,82]. A preventive, single-arm study without a placebo-group due to ethical reasons included 89 asymptomatic patients (4.7±4.1 years of age), who were treated with LO and moderate fat restriction diet and who were followed up for 6.9±2.7 years.…”

Section: Therapymentioning

confidence: 99%

Therapy of X-linked adrenoleukodystrophy

Semmler

Köhler

Jung

et al. 2008

Expert Review of Neurotherapeutics

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X-linked adrenoleukodystrophy (X-ALD; OMIM #300100) is caused by defects of the ABCD1 gene on chromosome Xq28, resulting in an impairment of peroxisomal beta-oxidation and the accumulation of saturated very long chain fatty acids (VLCFAs). Primary manifestations occur in the CNS, the adrenal cortex and the testes' Leydig cells. The clinical presentation shows a marked variability which is not explained by the different X-ALD genotypes. Phenotypes range from rapidly progressive cerebral disease with childhood (childhood cerebral ALD [CCALD]) or adulthood (adult cerebral ALD [ACALD]) onset leading to death within a few years, over adult-onset adrenomyeloneuropathy (AMN) with or without focal CNS demyelination, AMN converting into a rapidly progressive, cerebral demyelinating phenotype resembling CCALD, to slow disease progression over decades, or adrenal insufficiency only. Approximately 50% of female heterozygotes develop moderate spastic paresis resembling the AMN phenotype. This review focuses on current experiences with different therapeutic approaches. Lorenzo's oil did not prove to be effective in cerebral inflammatory disease variants, but asymptomatic patients, and speculatively AMN variants without cerebral involvement, as well as female carriers may benefit from early intake of oleic and erucic acids in addition to VLCFA restriction. Hormone-replacement therapy is necessary in all patients with adrenal insufficiency. Hematopoietic stem cell transplantation has been reported to be effective in presymptomatic or early symptomatic CCALD, and may well also be a final therapeutic option in early ACALD patients. Early detection of mutation carriers and timely initiation of therapy is important for the effectiveness of all therapeutic efforts. Gene therapy of endogenous hematopoietic stem cells, pharmacological upregulation of other genes encoding proteins involved in peroxisomal beta-oxidation, reduction of oxidative stress, and possibly lovastatin are candidates for future X-ALD therapies. Future Drugs Ltd: Peer Review PaperPlease return your comments for the attention of the Commissioning Editor at l.tipton@expert-reviews.com Many thanks in advance for your kind assistance. Therapy of X-linked Adrenoleukodystrophy Future Drugs Ltd: Peer Review PaperPlease return your comments for the attention of the Commissioning Editor at l.tipton@expert-reviews.com Many thanks in advance for your kind assistance. et al 1963 [6]. In 1981 the X-ALD locus was mapped to chromosome Xq28 [7], and twelve years later, the X-ALD gene (ABCD1) was identified [8,9]. Today X-ALD has been identified in most countries worldwide and in most ethnic groups. The minimum frequency of hemizygotes in the UnitedStates was determined to be 1:42,000 and the one of hemizygotes plus heterozygotes 1:16,800, suggesting X-ALD as the most common inherited leukodystrophy [10]. X-ALD phenotypesX-ALD is characterized by a highly variable clinical spectrum, from early progressive childhood to mild adulthood disease with only slow symptom progre...

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Follow-up of 89 Asymptomatic Patients With Adrenoleukodystrophy Treated With Lorenzo’s Oil

Moser¹,

Raymond²,

Lu³

et al. 2005

Arch Neurol

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211

110

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Objectives:To identify asymptomatic boys with Xlinked adrenoleukodystrophy who have a normal magnetic resonance image (MRI), and to assess the effect of 4:1 glyceryl trioleate-glyceryl trierucate (Lorenzo's oil) on disease progression.Method: Eighty-nine boys (mean ± SD baseline age, 4.7±4.1 years; range, 0.2-15 years) were identified by a plasma very long-chain fatty acids assay used to screen at-risk boys. All were treated with Lorenzo's oil and moderate fat restriction. Plasma fatty acids and clinical status were followed for 6.9 ± 2.7 years. Changes in plasma hexacosanoic acid levels were assessed by measuring the length-adjusted area under the curve, and a proportional hazards model was used to evaluate association with the development of abnormal MRI results and neurological abnormalities.Results: Of the 89 boys, 24% developed MRI abnormalities and 11% developed both neurological and MRI

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Evaluation of the Preventive Effect of Glyceryl Trioleate-Trierucate (“Lorenzo’s Oil”) Therapy in X-Linked Adrenoleukodystrophy: Results of Two Concurrent Trials

Cited by 55 publications

References 27 publications

Uptake and metabolism of plasma-derived erucic acid by rat brain

Uptake and metabolism of plasma-derived erucic acid by rat brain

Therapy of X-linked adrenoleukodystrophy

Follow-up of 89 Asymptomatic Patients With Adrenoleukodystrophy Treated With Lorenzo’s Oil

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