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

Abstract

X-linked adrenoleukodystrophy (X-ALD) is characterized by progressive neurological disability and primary adrenocortical insufficiency as a consequence of mutations in the ABCD1 gene that encodes a peroxisomal ATP binding cassette protein (Moseret al 2000a; Kempet al 2001) with a minimum incidence of 1:17,000 (Bezman et al. 2001). More than 400 different mutations have been identified (Kemp et al 2001). It is associated with the accumulation of saturated very long chain fatty acids, principally hexacosanoic (C26:0) and tetracosanoic acid (C24:0). High levels of these fatty acids are present in plasma (Moser et al 1999a). The neurologic manifestations show a wide range of severity. The childhood cerebral form (CCER) often leads to total disability and death by 10 years of age. Adrenomyeloneuropathy (AMN) presents as a paraparesis in young adults and progresses slowly (Powers et al 2000). Members of a family often have widely varying phenotypes. It is not possible to predict future course in asymptomatic young boys on the basis of mutation analysis, concentrations of VLCFA in plasma or cultured skin fibroblasts or phenotype in family members. The adrenal insufficiency in X-ALD can be treated successfully with steroid replacement therapy but apparently this does not alter the progression of the neurologic disease (Moser et al 2000a). Bone marrow transplantation (BMT) has been found to be of long-term benefit in boys and adolescents with cerebral involvement (Shapiro et al. 2000), but carries a high risk and is most effective when cerebral involvement is still mild.