Contact: Priscille Riviere
[email protected]
INSERM (Institut national de la santé et de la recherche médicale)
Taurine: Key to the visual toxicity of an anti-epileptic drug for children?
Vigabatrin (Sabril), first intention
molecule for the treatment of epilepsy in children, in many cases
produces secondary effects that lead to an irreversible loss of vision.
Serge Picaud, head of research at Inserm, and his colleagues of the
Institut de la Vision have just discovered the origin of this secondary
effect and have proposed strategies for limiting it. They have shown
that vigabatrin provokes a marked decrease in the blood level in an
amino acid, taurine, resulting in a degeneration of the retina cells
induced by light. The researchers therefore suggest that exposure to
light should be reduced and a taurine-rich diet introduced in order to
curb immediately these secondary effects in children undergoing
treatment. As for the validation of an alternative treatment
associating vigabatrin and taurine, this will necessitate several years
of development.
This work is published in the review
Annals of Neurology.
Epilepsy affects 1% of the world's population. With children, its
treatment remains extremely restricted, and vigabatrin, (marketed in
France under the name of Sabril®), has obtained marketing authorisation
for children aged under 2 years. This anticonvulsant, which is also
administered to adults in the case of failure of other treatments, is
at the same time now being evaluated for the treatment of addiction to
heroin, cocaine and methamphetamines.
However, the serious secondary effects of this drug can induce an
impairment of the retina and a restriction of the visual field, noted,
depending on the studies, in 10% to 40% of patients.
In order to reach an understanding of this drug's modes of actions,
and in particular the mechanism of visual function impairment, the
Inserm researchers first of all administered vigabatrin to rats over a
period of several months and analysed the influence of exposure to
light during the treatment. The results show that there is no damage to
the retina when the animals are kept in the dark throughout the
treatment.
Moreover, since previous work had shown that a deficiency of the
organism in taurine (amino acid) triggers the degeneration of the
photoreceptors (cells of the retina converting light into nervous
signals), the researchers measured, in rodents, the plasma level of 19
amino acids. Whereas the concentration was identical for most of the
amino acids in animals under vigabatrin and in non-treated rats, the
taurine level turned out to be 67% lower in treated animals
Taurine is essentially contributed by diet. By providing certain of
the animals under treatment with a taurine supplementation, the
researchers noted that their visual acuity was greater than that of the
animals without supplementation. In addition, the amino acid doses
administered to six children subject to regular attacks of epilepsy and
treated under vigabatrin reveal a taurine level that is far below the
normal values reported for children of the same age – and in some cases
even undetectable.
On the strength of these various tests, the
scientists were able to prove that vigabatrin induces a pronounced
reduction of the taurine level in the plasma. This marked fall is
responsible for the degeneration of the photoreceptors and thus for the
retinal toxicity in the animals exposed to light.
Pending confirmation in the human of the interest of providing
patients under vigabatrin with a taurine supplementation, the
researchers propose immediate solutions designed to limit the secondary
effects in these patients. "In the first instance, care should
therefore be taken to ensure that patients under vigabatrin consume a
sufficient amount of food containing taurine. It is also important that
they should be exposed to as little light as possible (e.g.; no night
lights in a baby's bedroom at night) and should be induced to wear
sunglasses", says Serge Picaud.
The researchers also emphasise that any taurine supplementation must be subject to medical advice.
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To find out more:
Firas Jammoul MD1,2, Qingping Wang MD1,2,3, Rima Nabbout
MD4,5,6, Caroline Coriat MD1,2, Agnès Duboc PhD1,2, Manuel
Simonutti1,2, Elisabeth Dubus1,2, Cheryl M. Craft PhD7, Wen Ye MD3,
Stephen D. Collins MD PhD8 , Olivier Dulac MD4,5,6, Catherine Chiron
MD4,5,6, José A. Sahel MD1,2,9,10, Serge Picaud PhD1,2,10,11
1 Inserm, U592, Institut de la Vision, Paris, France
2 Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France
;3 Fudan University, Ophthalmology Department, Huashan Hospital,
Shanghai, China
4 Inserm, U663, Paris, France
5 University Rene Descartes, Paris V, Paris, France
6 APHP, Hopital Necker, Service de Neuropédiatrie, Paris, France
7Ophthalmology and Cell & Neurobiology Departments, Keck School of Medicine of the
University of Southern California, and The Mary D. Allen Laboratory for Vision Research,
Doheny Eye Institute, Los Angeles, USA
8 Ovation Pharmaceuticals, Deerfield, USA
9 Centre Hospitalier National d'Ophtalmologie des quinze-vingts, Paris, France;
10Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
11Assistance Publique-Hopitaux de Paris, France
Annals of neurology DOI: http://dx.doi.org/10.1002/ana.21526
Published Online: 4 Feb 2009
Research contacts:
Serge Picaud
Institut de la Vision,
Email : [email protected]