Taurine: Key to the visual toxicity of an anti-epileptic drug for children?

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February 17, 2009

Source: INSERM (Institut national de la santé et de la recherche médicale)

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 ls 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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