The Experts below are selected from a list of 6 Experts worldwide ranked by ideXlab platform

Hildegard Buning - One of the best experts on this subject based on the ideXlab platform.

  • 435 adeno associated virus vectors are able to restore faldh deficiency in cells of Sjoegren Larsson Syndrome
    Molecular Therapy, 2004
    Co-Authors: Markus Braunfalco, Stefanie Haug, Hildegard Buning
    Abstract:

    Sjoegren-Larsson Syndrome (SLS) is caused by an autosomal recessive defect in the gene coding for fatty aldehyde dehydrogenase (FALDH), an enzyme necessary for the oxidation of long-chain aliphatic aldehydes to fatty acids as part of the fatty alcohol:nicotinamide-adenine dinucleotide (NAD+)-oxidoreductase complex (FAO). The impaired activity of FALDH leads to the clinical triad of generalized ichthyosis, mental retardation, and spastic diplegia or tetraplegia. In order to develop a gene therapy approach for the treatment of SLS, we constructed a recombinant adeno-associated virus vector containing the human cDNA of functional FALDH (rAAV/C-FALDH) and evaluated its capability to restore the enzyme deficiency. First, we transduced a FALDH-deficient Chinese hamster ovary (CHO) mutant resembling the gene defect of SLS. Transduction with rAAV/C-FALDH of FALDH-deficient CHO cells, usually exhibiting less than 10% of normal FALDH activity, resulted in an increase of FALDH activity of up to 80% and more of the activity of unaffected cells. Next, we isolated keratinocytes from SLS-patients and measured their FALDH activity in comparison to keratinocytes of unaffected individuals. The diagnosis of SLS-keratinocytes could be approved by a reduction of FALDH activity below 15% of normal. The SLS-keratinocytes were transduced with rAAV/C-FALDH and rAAV/C-GFP particles as a negative control. FALDH activity of FALDH transduced SLS-keratinocytes was markedly increased in comparison to GFP-transduced SLS-keratinocytes. The level of activity was above 50% of normal and reached the level of heterozygous phenotypically normal carriers. These results indicated that rAAV vectors are able to restore FALDH deficiency in vitro, supporting the concept that gene therapy might be a possible approach for the treatment of SLS.

Markus Braunfalco - One of the best experts on this subject based on the ideXlab platform.

  • 435 adeno associated virus vectors are able to restore faldh deficiency in cells of Sjoegren Larsson Syndrome
    Molecular Therapy, 2004
    Co-Authors: Markus Braunfalco, Stefanie Haug, Hildegard Buning
    Abstract:

    Sjoegren-Larsson Syndrome (SLS) is caused by an autosomal recessive defect in the gene coding for fatty aldehyde dehydrogenase (FALDH), an enzyme necessary for the oxidation of long-chain aliphatic aldehydes to fatty acids as part of the fatty alcohol:nicotinamide-adenine dinucleotide (NAD+)-oxidoreductase complex (FAO). The impaired activity of FALDH leads to the clinical triad of generalized ichthyosis, mental retardation, and spastic diplegia or tetraplegia. In order to develop a gene therapy approach for the treatment of SLS, we constructed a recombinant adeno-associated virus vector containing the human cDNA of functional FALDH (rAAV/C-FALDH) and evaluated its capability to restore the enzyme deficiency. First, we transduced a FALDH-deficient Chinese hamster ovary (CHO) mutant resembling the gene defect of SLS. Transduction with rAAV/C-FALDH of FALDH-deficient CHO cells, usually exhibiting less than 10% of normal FALDH activity, resulted in an increase of FALDH activity of up to 80% and more of the activity of unaffected cells. Next, we isolated keratinocytes from SLS-patients and measured their FALDH activity in comparison to keratinocytes of unaffected individuals. The diagnosis of SLS-keratinocytes could be approved by a reduction of FALDH activity below 15% of normal. The SLS-keratinocytes were transduced with rAAV/C-FALDH and rAAV/C-GFP particles as a negative control. FALDH activity of FALDH transduced SLS-keratinocytes was markedly increased in comparison to GFP-transduced SLS-keratinocytes. The level of activity was above 50% of normal and reached the level of heterozygous phenotypically normal carriers. These results indicated that rAAV vectors are able to restore FALDH deficiency in vitro, supporting the concept that gene therapy might be a possible approach for the treatment of SLS.

Stefanie Haug - One of the best experts on this subject based on the ideXlab platform.

  • 435 adeno associated virus vectors are able to restore faldh deficiency in cells of Sjoegren Larsson Syndrome
    Molecular Therapy, 2004
    Co-Authors: Markus Braunfalco, Stefanie Haug, Hildegard Buning
    Abstract:

    Sjoegren-Larsson Syndrome (SLS) is caused by an autosomal recessive defect in the gene coding for fatty aldehyde dehydrogenase (FALDH), an enzyme necessary for the oxidation of long-chain aliphatic aldehydes to fatty acids as part of the fatty alcohol:nicotinamide-adenine dinucleotide (NAD+)-oxidoreductase complex (FAO). The impaired activity of FALDH leads to the clinical triad of generalized ichthyosis, mental retardation, and spastic diplegia or tetraplegia. In order to develop a gene therapy approach for the treatment of SLS, we constructed a recombinant adeno-associated virus vector containing the human cDNA of functional FALDH (rAAV/C-FALDH) and evaluated its capability to restore the enzyme deficiency. First, we transduced a FALDH-deficient Chinese hamster ovary (CHO) mutant resembling the gene defect of SLS. Transduction with rAAV/C-FALDH of FALDH-deficient CHO cells, usually exhibiting less than 10% of normal FALDH activity, resulted in an increase of FALDH activity of up to 80% and more of the activity of unaffected cells. Next, we isolated keratinocytes from SLS-patients and measured their FALDH activity in comparison to keratinocytes of unaffected individuals. The diagnosis of SLS-keratinocytes could be approved by a reduction of FALDH activity below 15% of normal. The SLS-keratinocytes were transduced with rAAV/C-FALDH and rAAV/C-GFP particles as a negative control. FALDH activity of FALDH transduced SLS-keratinocytes was markedly increased in comparison to GFP-transduced SLS-keratinocytes. The level of activity was above 50% of normal and reached the level of heterozygous phenotypically normal carriers. These results indicated that rAAV vectors are able to restore FALDH deficiency in vitro, supporting the concept that gene therapy might be a possible approach for the treatment of SLS.

A Sillen - One of the best experts on this subject based on the ideXlab platform.

  • strong allelic association between Sjoegren Larsson Syndrome and d17s805
    American Journal of Human Genetics, 1994
    Co-Authors: M Pigg, S Jagell, A Sillen
    Abstract:

    Sjoegren-Larsson Syndrom (SLS) is characterized by congenital ichthyosis, spastic di- or tetraplegia and mental retardation. It is an autosomal recessive trait that has been described in many populations, but is particularly frequent in the northern part of Sweden. A defect in the enzyme fatty alcohol: NAD+ oxidoreductase (FAD) has been suggested, but the molecular mechanism has not been elucidated. Based on linkage analysis and allelic association, the disorder has now been mapped to chromosome 17. Meiotic recombinations suggests that the gene is flanked by D17S805 on the centromeric and D17S783 and D17S925 on the telomeric side. These three markers map to the same location in reference pedigrees. Strong allelic association (chi-square 60.28, p<0.0003) to D17S805 suggests that the mutation is located at a limited distance on the telomeric side of this marker. It is possible that the gene can be identified by functional complementation of SLS cells using YACs from this region. Alternatively, positional cloning should be possible in this presumable small area. The markers identified are close and informative enough to allow accurate genetic diagnosis.

M Pigg - One of the best experts on this subject based on the ideXlab platform.

  • strong allelic association between Sjoegren Larsson Syndrome and d17s805
    American Journal of Human Genetics, 1994
    Co-Authors: M Pigg, S Jagell, A Sillen
    Abstract:

    Sjoegren-Larsson Syndrom (SLS) is characterized by congenital ichthyosis, spastic di- or tetraplegia and mental retardation. It is an autosomal recessive trait that has been described in many populations, but is particularly frequent in the northern part of Sweden. A defect in the enzyme fatty alcohol: NAD+ oxidoreductase (FAD) has been suggested, but the molecular mechanism has not been elucidated. Based on linkage analysis and allelic association, the disorder has now been mapped to chromosome 17. Meiotic recombinations suggests that the gene is flanked by D17S805 on the centromeric and D17S783 and D17S925 on the telomeric side. These three markers map to the same location in reference pedigrees. Strong allelic association (chi-square 60.28, p<0.0003) to D17S805 suggests that the mutation is located at a limited distance on the telomeric side of this marker. It is possible that the gene can be identified by functional complementation of SLS cells using YACs from this region. Alternatively, positional cloning should be possible in this presumable small area. The markers identified are close and informative enough to allow accurate genetic diagnosis.