The scientific conference devoted to genetic therapy in metachromatic leukodystrophy treatment in late infancy form was held in Paris in April 16-17.2011. It was organized by European Leukodytrophy Association (ELA). This organization supports families of children suffering from leukodytrophy and ELA enables them gaining financial help.
Infancy form of metachromatic leukodystrophy is 2/3 of all metachromatic leukodystrophy cases. The most frequent cause of this disease is mutation in gene coding arylsulfatase G>A (ARSA) which is located in the long arm of 22nd chromosome. The lack of ARSA or this enzyme leads to creating abnormal myelin sheath, demyelination in central and peripheral nervous system and what is more, to the loss of white matter in the brain. Up to 15 months this disease is symptomless. When the activity of arylsulfatase is lowering to 10% under its activity in healthy patients, various symptoms may appear. Serious neurological and psychological symptoms appear in later periods. In the first stage of the disease there may appear problems with walking, psychosomatic retardation, weakening and muscles hypotony. In the second stage there is the increase in muscles strain, superficial reflexes in upper limbs. There are also present cerebellum symptoms, nervousness, apathy and disorders in action. In the third stage there are intense symptoms of peripheral neuropathy and spastic limb paresis. There are sight atrophy, pseudobulbar palsy symptoms and sometimes epilepsy attacks, and speech disorders in dysarthria type. In the last stage the contact with the environment is completely impossible- the patient is blind, deaf, there appears decerebration and the lack of thermoregulation. Without special medical treatment the child dies when it is 3 years old due to the cerebral decortications and devastation. Due to rehabilitation the child can live up to 10 years old.
During the conference the clinical tests results taken in Copenhagen, Denmark from 2007 to 2010 were presented. Children from a few countries aged from 2 to 5 took part in researches to develop the first medicine for metachromatic leukodystrophy with the usage of enzymatic replacement therapy. With the genetic engineering methods hamster cells were transfected with the fragments of correct gene from healthy donors and pure arylsulfatase was obtained. 3 doses of medicines were given to the young patients intravenously. One group received dose of 50 units/kg of body weight. The second group received 100 units/kg body weight and the third 200. One child resigned from the research because of logistic problems. 50 mg of arylsulfatase given intravenously every second week costs 16 000 USD. The trial finished on 29.09.2010.
The next attempt is planned on the year 2013 in the USA by Shire HGT. Children with no symptoms would be involved in the research. This time the dose will be bigger and given every week into central nervous system. The enzyme will be obtained from human cells.
The hope for the treatment is also bone marrow transplantation (BMT), but only in children with no symptoms and a therapy based on introducing correct ARSA gene into fibroblast and hematopetic cells of the spinal cord with the viral vectors. Despite the fact that until now the results of leukodystrophy treatment are not as the patients’ mother would dream of, the engagement of researchers let us believe in positive development of new therapies.
Written by: Véronique Petit, Janusz Kocki
Department of Clinical Genetics of Medical University in Lublin, Poland
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