Fig. 2: Effects of allo-HSCT and gene therapy on inflammatory CALD lesions. | Nature Communications

Fig. 2: Effects of allo-HSCT and gene therapy on inflammatory CALD lesions.

From: Hematopoietic stem-cell gene therapy is associated with restored white matter microvascular function in cerebral adrenoleukodystrophy

Fig. 2

a Representative T1-weighted images without (T1W) and with gadolinium contrast enhancement (T1W CE), the apparent contrast leakage parameter (Kapp) and capillary flow heterogeneity (CTH) maps of two CALD patients before (PRE) and after (POST) treatment with allogenic hematopoietic stem-cell transplantation (allo-HSCT, left) or gene therapy (GT, right). Lesion magnifications in PRE show strong CE ring enhancement which resolved POST treatment in both patients, while POST Kapp- and CTH maps show persisting regionally increased BBB-permeability and microvascular flow heterogeneity in the allo-HSCT patient, in contrast to a GT-treated patient with rapid normalization of microvascular perfusion markers. Data points of these patients are highlighted with pointing triangles in the following figures. b Longitudinal data on binary contrast reads (yes vs. no pathologic CE) in GT patients (n = 15). c Lesional relative Kapp PRE and 2Y post GT (n = 13) and allo-HSCT (n = 8) and relative Kapp in corresponding white matter in age-matched hemizygotes without CALD (HEM, n = 11–8). Error bars show mean ± SD; the P values were determined by two-tailed paired and unpaired students’ t tests. d Comparison of lesional Kapp in patients assessed positive (CE+) and negative (CE−) for pathologic enhancement at 1Y (n = 5–10). Error bars show mean ± SD; two-tailed unpaired students’ t tests. e Same as c for CALD patients with self-arrested lesions (SA, n = 7) vs. age-matched HEM (n = 7). Two-tailed unpaired students’ t tests. f Plot showing the relationship of Kapp at 1Y and relative monthly FA decrease between the first month POST (V1) and 1Y (n = 15). Line indicates regression; two-tailed Pearson’s correlation. g Perilesional rCTH PRE and 2Y post GT (n = 13) and allo-HSCT (n = 10) and rCTH in corresponding white matter in age-matched hemizygotes without CALD (HEM, n = 11–10) Error bars show mean ± SD; the P values were determined by two-tailed paired and unpaired students’ t tests. h Correlation plot showing perilesional rCTH 1Y and relative monthly T2W lesion growth between the first month POST (V1) and 1Y (n = 15). Line indicates regression; two-tailed Pearson’s correlation. Source data are provided as a Source Data file.

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