Lorenzo's oil

Lorenzo's oil is a 4:1 mixture of glycerol trioleate and glycerol trierucate (the triglyceride forms of oleic and erucic acid) used in the preventative treatment of adrenoleukodystrophy (ALD). The oil was formulated by Augusto and Michaela Odone after their son Lorenzo was diagnosed with the disease in 1984, at the age of five. Augusto received U.S. Patent No. 5,331,009 for the oil. The royalties he now receives are paid to the Myelin Project which he and Michaela founded to further research treatments for ALD and similar disorders. The Odones and their invention obtained widespread publicity in 1992 because of the movie Lorenzo's Oil.

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Cost and reimbursement

Lorenzo's oil is expensive, costing approximately US$440 for a month's treatment. Most insurance companies will not pay for it since it is considered an experimental treatment by the FDA.

Mechanism of action

This mixture of fatty acids reduces the levels of very long chain fatty acids (VLCFA) known to cause ALD. It does so by competitively inhibiting the enzyme that forms VLCFAs.

Effectiveness

For those boys who have elevated long chain fatty acids, but who do not exhibit neurologic symptoms or an abnormal MRI, the treatment of choice is Lorenzo’s Oil (LO; Moser et al, 2003; Moser et al., Arch Neurol. 2005; 62(7):1073-80) together with a very low fat diet and, where appropriate, corticosteroids. LO, which is administered daily, is a mixture of glycerol trierucerin and glycerol triolein, 1:4. It is thought to act by reducing plasma levels of very long chain saturated fatty acids (Moser et al., Ann Neurol. 1987; 21(3):240-9). The clinical studies of LO have been criticized because, for ethical reasons, they did not compare treatment with placebo control groups. Rather, the benchmark was patient compliance, as measured by control of plasma very long chain fatty acids. That is, the outcome for patients whose very long chain fatty acids remained poorly controlled was compared to that for patients who were well controlled. While LO appears to be effective in preventing the onset of neuroinflammation, it is not able to reverse it, once initiated (van Geel et al., J Neurol Neurosurg Psychiatry. 1999; 67(3):290-9). Patients on LO therapy must be carefully monitored, as trieucerin has been reported to reduce platelet counts (platelets are needed to make blood clot properly; Konijnenberg et al., Platelets. 1998; 9:41-8).

For those boys with an abnormal MRI or who exhibit minor neurologic symptoms, the only effective treatment currently available is heterologous bone marrow transplant (Mahmood et al., Lancet Neurol. 2007; 6(8):687-92). This procedure was initiated in an attempt to arrest the inflammation characteristic of childhood ALD, and prevent further destruction of brain myelin. While it meets with mixed results (Peters et al, Blood. 2004; 104(3):881-8), bone marrow transplant has been reported to lead to restoration of neurologic function in some ALD patients (Shapiro et al., Lancet. 2000; 356(9231):713-8). Most recently, Aubourg has reported success with transplant of the ALD gene, using HIV virus as the vector.

Studies

In an early study, Duchesne studied eight males and reported improvements in follow-up magnetic resonance imaging of the brain.

In the only clinical study with positive findings, Moser tried Lorenzo's oil in 53 asymptomatic patients with ALD. Analysis of the effect of the oil indicated that there was only a slight but statistically significant slowing of clinical progression and delay of death.

A controlled study by Moser concluded that Lorenzo's oil does not alter the course of the illness in symptomatic patients; however, dietary therapy started before the development of symptoms may reduce the frequency and severity of subsequent neurological disability.

A study by Poulos found that Lorenzo's oil is of limited value in correcting the accumulation of saturated VLCFAs in the brain of patients with ALD.^[1]

In the best study so far, Aubourg reported in the New England Journal of Medicine the results of an open trial of treatment with Lorenzo's oil in 14 men with adrenomyeloneuropathy, five symptomatic heterozygous women, and five boys (mean age, 13 years) with preclinical ALD. Over a mean follow-up of 33 months, none of the 14 men with ALD improved, one of the five asymptomatic boys developed signs of myelopathy, and there were no changes in the symptomatic heterozygous women. The authors concluded that this open trial found no evidence of a clinically relevant benefit from dietary treatment with Lorenzo's oil in patients with ALD.^[2]

A 2005 study by Moser et al in the journal Archives of Neurology examined the effectiveness of Lorenzo's oil and moderate fat restriction on 89 asymptomatic boys at risk for ALD. After 7 years of treatment 24% of the boys developed MRI abnormalities and 11% developed both neurological and MRI abnormalities. The study demonstrated a significant association between the development of MRI abnormalities and a plasma hexacosanoic acid increase. The researchers concluded that Lorenzo's oil therapy be given to asymptomatic boys with X-linked adrenoleukodystophy who have normal brain MRI results to delay the onset of disease ^[3]. Comparative autopsies showed that treatment enriched erucic acid in plasma and tissues, but not in the brain.^[4]

Current state

In summary, although dietary manipulation using Lorenzo's oil has been shown to change blood test results, it appears to be ineffective for the symptomatic ALD even though some parents of ALD patients feel otherwise. However, recent studies by Dr. Hugo Moser have found evidence that use of the oil by asymptomatic patients may delay the onset of symptoms significantly.

In the U.S., Lorenzo’s oil is currently only available to patients taking part in a clinical trial at the Kennedy Krieger Institute. This trial was formerly held under the direction of Dr. Hugo Moser, until Moser's death in 2007.^[5] Moser's team, Dr. Gerald Raymond and Ann Moser continue the trial and his work with the leukodystrophies.

References