Progression of X-linked adrenoleukodystrophy under interferon-beta therapy

Abstract

The cerebral phenotype of X-linked adrenoleukodystrophy (ALD) is a rapidly progressive neurodegenerative disorder characterized by a cerebral inflammatory response and elevated very long-chain fatty acids (VLCFA). Interferon-beta (INFB) is known to suppress the synthesis of tumour necrosis factor alpha and interferon-gamma, which have been reported to be elevated in the margin of the areas of demyelination in ALD brains. We report on treatment with interferon-beta in 8 patients with cerebral ALD, who additionally received glycerol trioleate/glycerol trierucate. INFB-1 a (Rebif, Serono, Switzerland) was given subcutaneously once a week, 3 million units for the first 3 months and 6 million units for the next 9 months. All patients showed an unimpeded progression of neurological symptoms during INFB therapy. Therapy was stopped within 6 months in 4 patients because of the fast neurological deterioration with loss of walking. In all patients the MRI demonstrated a progression of demyelination with a qualitatively unchanged gadolinium enhancement. Further studies are needed to elucidate the pathomechanism of demyelination in ALD in order to find an effective therapy for cerebral ALD patients.