We propose to conduct a double-masked placebo controlled study of Glyceryl Trioleate-Glyceryl Trierucate (Lorenzo's Oil (LO) therapy in Adrenomyeloneupathy (AMN), the adult form of X-linked adrenoleukodystrophy (X-ALD). AMN is slowly progressive. It is a distal axonopathy that involves the long tracts of the spinal cord and differs from the rapidly progressive inflammatory cerebral forms that most commonly affect boys and adolescents. All forms of X- ALD are associated with the abnormal accumulation of very long chain fatty acids (VLCFA) in plasma and tissues The oral administration of LO normalizes plasma VLGFA levels in X-ALD patients within four weeks, and various therapeutic trials have been conducted during the last 14 years. While previous therapeutic trials of LO in patients with the cerebral forms of X-ALD were disappointing, recent studies suggest that it is beneficial in two types of X-ALD 1) as a preventive of neurological involvement in asymptomatic boys, and 2) in AMN where it appears to slow the rate of progression. None of the previous studies have been controlled and we now propose the first placebo-controlled trial. It will be a three-year study that will involve 120 men with AMN who do not have evidence of cerebral involvement and 120 women who are heterozygous for X-ALD and have an AMN-like syndrome. The study will be conducted at the Kennedy Krieger Institute and the General Clinical Research Center at the Johns Hopkins Medical Institutions. The study will be coordinated by Westat. The rate of progression will be compared in the LO and placebo groups. The Kurtzke EDDS score will be the primary outcome measure. A variety of secondary outcome measures will also be used. A novel part of the study is the utilization and validation of newly developed markers, namely quantitative tests of sensation, strength and balance in the motion analysis laboratory, and magnetic transfer imaging studies of the dorsal columns in the cervical cord. These markers test the function and structure of the parts of the nervous system that are most severely involved in AMN. Our preliminary studies suggest that they may permit more sensitive and rapid assessment of the rate of progression than can be achieved with current techniques. This would facilitate and speed the evaluation of all therapeutic interventions in AMN. These techniques may also be applicable to the study of other spinal cord disorders. ? ? ?
