A medicine for epilepsy has proved its effectiveness against a severe neurodegenerative disease


The X-linked adrenoleukodystrophy is a hereditary disorder that destroys the myelin (the white substance that covers and protects the nerves) of the central or the peripheral nervous system and that consequently produces a hormonal disorder. The disease is quite rare and affects only male humans, despite carrier women can only show some of the symptoms. Its incidence is of one case every 17.000 men. It is the most frequent kind of leukodystrophy and the main disorder of the peroxisome (part of the cell in charge of the elimination of toxic products).

The disease became known and famous in 1992 with the film Lorenzo’s oil, starred by Nick Nolte and Susan Sarandon.

Accumulation of fatty acids

The patients affected by the X-linked adrenoleukodystrophy have got a genetic mutation which prevents them from correctly degrading the fatty contained inside the cells. That effect provokes the accumulation of long-chained fatty acids in the blood and the tissues, especially in the brain and the suprarrenal glandula, which causes severe lesions.

The disease appears in two forms: one sudden and devastating childhood brain variation which provokes the death in only a few years, and another adult variation (known as adrenomyeloneuropathy) which evolutes slowlier. The childhood form is characterized by a severe brain demyelinisation and a neuroinflammation, whereas the adult form shows an axonal degeneration (the axons are the part of the neurons in charge of the signal transmission) but without signs neuroinflammation, and it affects mainly the spinal cord. Both variations share the same origin, but the reason why it has got different ways of affecting people is still unknown.

X-linked adrenoleukodystrophy is provoked by a mutation in the ABCD1 gene, which is involved in the long-chain fatty acid transportation inside the peroxisomes of the cells. In normal conditions, the peroxisome shortens the long-chain fatty acid and prepares them so that the cell can metabolize them correctly. The mutation in the ABCD1 gene hinders this process in such a way that the long-chain fatty acids accumulate in the tissues and in the blood and so damage the nervous cells.

The only treatment applicable nowadays is the transplant of haematopoyetic progenitors (bone medulla) of a compatible donor, despite it only works in a limited number of patients. Unluckily, those suffering the severe brain form with adrenomyeloneuropathy have no cure.


The research carried out by the IDIBELL researchers increases the hope of finding strategies to develop treatments against the disease. The research has shown that the valproic acid activates de ABCD2 gene (which works in a similar way to the ABCD1) and which succeeds in correcting the oxidation and reduction of the long-chain fatty acid concentration.

The researchers have proved the effectiveness of the medicine in a clinical assay carried out in five patients.

The coordinator of the research, Aurora Pujol, director of the Neurometabolic Disease group in IDIBELL, and researcher of ICREA and CIBERER, highlights that the “valproic acid is a promising treatment against the X-linked adrenoleukodystrophy, despite we have to carry out more research before approving its usual clinical application”.

Apart from IDIBELL, the paper published in Human Molecular Genetics has counted on the collaboration of several European research centers (Center for Molecular Medicine of Colonia, Germany; Institute of Neuropathology of Erlangen, Germany; Institute for Biomedical Research of Lleida; University of Ghent, Belgium; INSERM of Paris, and Emma’s Children’s Hospital of Amsterdam).

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