Evaluation of Therapy of X-Linked Adrenoleukodystrophy

* Special issue dedicated to Dr. Nicole A. Baumann. This article is dedicated to Dr. Nicole Baumann, who has made such major contributions to further understanding of the basic biology of metabolic and genetic disorders of the nervous system. One aspect that is particularly relevant to this particular article is that Dr. Baumann has also contributed greatly to the recognition and study of neurogenetic disorders that manifest in adulthood, and, most important, she has always striven to develop and evaluate therapies. Indeed, during the last decade our group has had the privilege of collaborating with Dr. Baumann and her associates in the evaluation of the therapy of X-linked adrenoleukodystrophy. 1 Division of Neurogenetics, Kennedy Krieger Institute, and the Departments of Neurology, Johns Hopkins University. 2 F. M. Kirby Center for Functional Neuroimaging, Kennedy Krieger Institute, and the Department of Radiology, Johns Hopkins University. 3 Westat, Rockville, Maryland. 4 Address reprint requests to: Hogo W. Moser. E-mail: moser@ kennedykrieger.org of therapeutic leads including diet, pharmacological agents, and transplant and gene therapy. Even though the first therapeutic trials were initiated more than 20 years ago (6), none of the approaches have been proven to be effective and safe, in part because objective and timely evaluation of therapies on the neurological and behavioral aspects of the disease is extraordinarily difficult. So far, the only therapy that is generally considered to be beneficial is bone marrow transplantation for a carefully characterized subgroup of patients (7). It is essential that new therapies be developed and validated because X-ALD is progressive and fatal, and it is relatively common (8). Furthermore, it is likely that tandem-mass spectrometry newborn screening techniques that are now being developed will identify a large number of affected male infants years before they develop symptoms. This will provide unique opportunities to prevent the tragic consequences of this illness and adds to the urgency of developing and validating new therapies.