Current and Future Pharmacological Treatment Strategies in X-Linked Adrenoleukodystrophy
Article first published online: 7 JUN 2010
© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology
Volume 20, Issue 4, pages 845–856, July 2010
How to Cite
Berger, J., Pujol, A., Aubourg, P. and Forss-Petter, S. (2010), Current and Future Pharmacological Treatment Strategies in X-Linked Adrenoleukodystrophy. Brain Pathology, 20: 845–856. doi: 10.1111/j.1750-3639.2010.00393.x
- Issue published online: 7 JUN 2010
- Article first published online: 7 JUN 2010
- Received 5 March 2010; accepted 8 March 2010.
- histone deacetylase inhibitor;
- Lorenzo's oil;
- valproic acid;
Mutations in the ABCD1 gene cause the clinical spectrum of the neurometabolic disorder X-linked adrenoleukodystrophy/adrenomyeloneuropathy (X-ALD/AMN). Currently, the most efficient therapeutic opportunity for patients with the cerebral form of X-ALD is hematopoietic stem cell transplantation and possibly gene therapy of autologous hematopoietic stem cells. Both treatments, however, are only accessible to a subset of X-ALD patients, mainly because of the lack of markers that can predict the onset of cerebral demyelination. Moreover, for female or male X-ALD patients with AMN, currently only unsatisfying therapeutic opportunities are available. Thus, this review focuses on current and urgently needed future pharmacological therapies. The treatment of adrenal and gonadal insufficiency is well established, whereas applications of immunomodulatory and immunosuppressive drugs have failed to prevent progression of cerebral neuroinflammation. The use of Lorenzo's oil and the inefficacy of lovastatin to normalize very-long-chain fatty acids in clinical trials as well as currently experimental and therefore possible future therapeutic strategies are reviewed. The latter include pharmacological gene therapy mediated by targeted upregulation of ABCD2, the closest homolog of ABCD1, antioxidative drug treatment, small molecule histone deacetylase inhibitors such as butyrates and valproic acid, and other neuroprotective attempts.