Adrenoleukodystrophy (ALD)
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00156-4
Cerebral adrenoleukodystrophy (cALD) is a form of a rare genetic condition in which very long-chain fatty acids (VLCFA) build up in the body. This can lead to inflammation and damage to myelin, which is the protective covering around nerve fibres in the brain. Two treatments can help slow or stop this damage: gene therapy using a patient’s own genetically modified stem cells, or a stem cell transplant from a healthy donor. To better understand how these treatments compare, researchers examined 21 boys who received gene therapy and 35 who received donor stem cell transplants. They measured two blood biomarkers, which are substances that can give clues about disease activity, before treatment and one year later. C26:0-lysophosphatidylcholine (C26:0-lysoPC) reflects the buildup of a VLCFA, while neurofilament light chain (NfL) can signify injury to nerve cells. Brain scans showed greater disease progression in the gene therapy group. After one year, C26:0-lysoPC levels and NfL levels greatly decreased following donor transplantation. C26:0-lysoPC levels decreased slightly in the gene therapy group but NfL levels increased significantly. Other published data has shown that 12 months after gene therapy, 10-20% of corrected myeloid cells (immune cells) express the ABCD1-encoded protein, ALDP while after Allo-HCT, 100% of cells express ALDP. These findings suggest that donor transplantation may lead to more favourable changes in these metabolic measures during the first year and measures in the gene therapy need further time to normalise. However, the study does not establish which treatment is best for every patient, and 12 months is relatively early when evaluating long-term treatment outcomes. Understanding these differences could help clinicians monitor treatment responses and improve future treatment approaches.