Management of adrenoleukodystrophy: From pre-clinical studies to the
development of new therapies
Abstract
X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative
disorder associated with mutations of the ABCD1 gene that encodes a
peroxisomal transmembrane protein. It results in accumulation of very
long chain fatty acids in tissues and body fluid. Along with other
factors such as epigenetic and environmental involvement, ABCD1
mutation-provoked disorders can present different phenotypes including
cerebral adrenoleukodystrophy (cALD), Adrenomyeloneuropathy (AMN), and
Addison’s disease. cALD is a life-threatening form that causes death in
young children. Bone marrow transplantation and hematopoietic stem cell
gene therapy are only effective when performed at an early stage of
onsets in cALD. Nonetheless, current research and development of novel
therapies are hampered by a lack of in-depth understanding disease
pathophysiology and a lack of reliable cALD models. The ABCD1- and
ABCD1-/ABCD2-/- mouse models and ABCD1- rabbit models created in our
lab, do not develop cALD phenotypes observed in human being. In this
review, we summarize the clinical and biochemical features of X-ALD, the
progress of pre-clinical and clinical studies. Challenges and
perspectives for future X-ALD studies are also discussed.