Advances in the treatment of adrenoleukodystrophy

doi:10.3969/j.issn.1674-8115.2025.01.011

Abstract

Abstract:

Adrenoleukodystrophy (ALD) is an X-linked, potentially fatal peroxisome disease, characterized by three main clinical phenotypes: adrenomyeloneuropathy (AMN), cerebral adrenoleukodystrophy (CALD), and primary adrenal insufficiency. The clinical phenotypes of ALD are unpredictable, with no genotype-phenotype correlation, and disease progression cannot be predicted based on very long chain fatty acid (VLCFA) levels in plasma. Additionally, the phenotypes can exhibit significant variability. Currently, no definitive treatment for this disease exists, and treatment options vary depending on the specific phenotypes. For AMN, only symptomatic supportive treatment is available. However, early CALD can be stabilized through allogeneic hematopoietic stem cell transplantation (allo-HSCT) and transgenic autologous hematopoietic stem cell transplantation (trans-ASCT), and primary adrenal insufficiency can be treated through hormone replacement therapy. Allo-HSCT and trans-ASCT can prevent the progression of early CALD, but cannot reverse the changes of AMN or halt the progression of adrenal insufficiency. Furthermore, they cannot prevent neurological dysfunction or death in terminal CALD. In recent years, multiple clinical trials of drugs targeting ALD have demonstrated therapeutic potential for ALD. Trans-ASCT and gene editing therapy have also made breakthroughs in animal models and clinical trials, providing alternative options for ALD patients ineligible for allo-HSCT treatment. This paper reviews the latest therapeutic research results of ALD and provides a basis for clinical practice.

Key words: adrenoleukodystrophy (ALD), cerebral adrenoleukodystrophy (CALD), adrenomyeloneuropathy (AMN), primary adrenal insufficiency, hematopoietic stem cell transplantation (HSCT)

CLC Number:

R742.8

LIU Xiaoli, CAO Li. Advances in the treatment of adrenoleukodystrophy[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(1): 95-100.

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