Breaking down ALD Investigating pathomechanisms using hiPSC-derived CNS models

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal neurometabolic disorder caused by pathogenic variants in the ABCD1 gene, resulting in impaired peroxisomal ß-oxidation and accumulation of very long-chain fatty acids (VLCFA). ALD clinical presentation is heterogeneous and unpredictable, including progressive spinal cord axonal degeneration, adrenal insufficiency, and leukodystrophy. Although VLCFA accumulation represents a clear biochemical hallmark of ALD, the cellular and molecular mechanisms linking this metabolic defect to the diverse