Visual evoked potentials in adrenolukodystrophy: A trial with glycerol trioleate and Lorenzo oil

Abstract

Adrenoleukodystrophy is an X-linked metabolic disorder with very-long-chain fatty acid (VLCFA) accumulation and multifocal nervous system demyelination, often with early involvement of visual pathways. Dietary therapy with glycerol trioleate and glycerol trierucate (Lorenzo oil) diminishes VLCFA levels. In a study of patients with the adrenomyeloneuropathy phenotype of adrenoleukodystrophy, we used pattern-reversal visual evoked potentials to evaluate visual pathways before and after treatment. Of 108 patients tested, all 26 women and 68 of the 82 men had normal potentials at baseline. Seventy patients were retested at 1 year, at which time VLCFA levels were markedly diminished. Of them, the responses in the 10 men who showed abnormalities at baseline remained abnormal; the latencies in 4 men with initially normal responses became abnormal. No patients improved. There were no correlations between disease duration prior to treatment, baseline P100 latencies, VLCFA levels, or the change in P100 latencies and VLCFA levels after dietary treatment for 1 year. Pattern-reversal visual evoked potentials were abnormal in 17% of the men with adrenoleukodystrophy, and there was no evidence that reduction of VLCFA levels improved or retarded visual pathway demyelination.

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

“…In patients with X-ALD, LO rapidly normalizes plasma VLCFA and effectively reduces tissue levels of VLCFA, except in the brain (36)(37)(38)(39)(40). These early, limited clinical trials suggested that 22:1n-9, the active component of LO, failed to cross the BBB (36,39,40), thereby accounting for the lack of efficacy in limiting the rapid progression of the demyelination in these patients.…”

“…Subsequent studies included glycerol trierucate in a treatment regimen referred to as Lorenzo's Oil (LO) (U.S. Patent number 5,331,009). This treatment normalized plasma 26:0 levels within 4 weeks but did not halt neurological deterioration in patients with advanced X-ALD (36)(37)(38). Postmortem analysis of tissue from these X-ALD patients treated with LO show that erucic acid (22:1n-9) was absorbed from the gut and found esterified into liver, adrenal glands, and adipose lipid pools, but brain levels of 22:1n-9 were not different between treatment groups (39,40).…”

Visual and Brainstem Auditory Evoked Potentials in Neurology

“…Kaplan et al, 1993 found that pattern-reversal VEPs were abnormal in 17% of patients with adrenoleukodystrophy; no evidence indicated that reduction of VLCFA levels improved or retarded visual pathway demyelination.…”

Therapy of X-linked adrenoleukodystrophy

“…A practical goal seems to be a reduction of VLCFA to normal plasma levels. gingivitis [85][86][87][88][89][90]. In addition to LO treatment a VCLFA-poor diet with fat restriction to 15% of the daily calories is applied.…”

“…A series of small clinical trials led to the conclusion that the intake of LO does not completely prevent the progression in all patients who are already neurologically symptomatic at initiation of the therapy [80,[87][88][89]108], however, in the absence of any controlled studies, it is not possible to determine whether the reported progression in some symptomatic patients differs from what one would expect in untreated patients. Moreover, most…”