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Genomes and Genes | Nina RabenSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
Autophagy and mitochondria in Pompe disease: nothing is so new as what has long been forgottenNina Raben
NIAMS, NIH, Bethesda, MD 20892 1820, USA
Am J Med Genet C Semin Med Genet 160:13-21. 2012..In this review, we will focus on these recent data, and comment on the not so recent observations pointing to the involvement of autophagy in skeletal muscle damage in Pompe disease...- Role of autophagy in the pathogenesis of Pompe diseaseN Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Acta Myol 26:45-8. 2007..These findings may explain why ERT often falls short of reversing the disease process, and point to new avenues for the development of pharmacological intervention... - Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder--murine Pompe diseaseNina Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Autophagy 6:1078-89. 2010..The suppression of autophagy, which has proven successful in the Pompe model, is a novel therapeutic approach that may be useful in other diseases with disturbed autophagy... - Differences in the predominance of lysosomal and autophagic pathologies between infants and adults with Pompe disease: implications for therapyNina Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1820, USA
Mol Genet Metab 101:324-31. 2010..In most fibers, the two pathologies did not seem to coexist. These data point to the possibility of differences in the pathogenesis of Pompe disease in infants and adults... - Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe diseaseTokiko Fukuda
Arthritis and Rheumatism Branch, Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Mol Ther 14:831-9. 2006..These findings may explain why ERT often falls short of reversing the disease process and point toward new avenues for the development of pharmacological intervention... - Murine muscle cell models for Pompe disease and their use in studying therapeutic approachesShoichi Takikita
Arthritis and Rheumatism Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, NIH, Building 50 Room 1345, 50 South Drive, Bethesda, MD 20892, USA
Mol Genet Metab 96:208-17. 2009.... 
Induction of tolerance to a recombinant human enzyme, acid alpha-glucosidase, in enzyme deficient knockout miceNina Raben
Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, 9000 Rockville Pike, Clinical Center Bld 10 9N244, Bethesda, MD 20892, USA
Transgenic Res 12:171-8. 2003..The study suggests that the induction of tolerance in animal models of protein deficiencies could be achieved by restricting the expression of a gene of interest to a particular, carefully chosen tissue...- When more is less: excess and deficiency of autophagy coexist in skeletal muscle in Pompe diseaseNina Raben
Arthritis and Rheumatism Branch, NIAMS, NIH, Bethesda, MD 20892 1820, USA
Autophagy 5:111-3. 2009..Also, by generating muscle-specific autophagy-deficient wild-type mice, we were able to analyze the role of autophagy in healthy skeletal muscle... - Fiber type conversion by PGC-1α activates lysosomal and autophagosomal biogenesis in both unaffected and Pompe skeletal muscleShoichi Takikita
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
PLoS ONE 5:e15239. 2010..These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy... - Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibersNina Raben
Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, 9000 Rockville Pike, Building 10 9N244, Bethesda, MD 20892, USA
Mol Ther 11:48-56. 2005..Low abundance of proteins involved in endocytosis and trafficking of lysosomal enzymes combined with increased autophagy in type II fibers may explain the resistance to therapy... - Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe diseaseNina Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1820, USA
Hum Mol Genet 17:3897-908. 2008..As a result, autophagic substrates, including potentially toxic aggregate-prone ubiquitinated proteins, accumulate in Pompe myofibers and may cause profound muscle damage... - Autophagy and lysosomes in Pompe diseaseTokiko Fukuda
Arthritis and Rheumatism Branch, Office of Science and Technology, NIAMS, National Institutes of Health, Bethesda, Maryland 20892-1820, USA
Autophagy 2:318-20. 2006.... - Dysfunction of endocytic and autophagic pathways in a lysosomal storage diseaseTokiko Fukuda
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820, USA
Ann Neurol 59:700-8. 2006..INTERPRETATION: The vastly increased autophagic buildup may be responsible for skeletal muscle damage and prevent efficient trafficking of replacement enzyme to lysosomes... - Impaired organization and function of myofilaments in single muscle fibers from a mouse model of Pompe diseaseSengen Xu
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bldg 50, Rm 1531, 9000 Rockville Pike, Bethesda, MD 20892, USA
J Appl Physiol 108:1383-8. 2010..The results are consistent with a disruption of actin and myosin interactions in the knockout muscles, demonstrating that impaired myofibrillar function contributes to weakness in the diseased muscle fibers... - Monitoring autophagy in lysosomal storage disordersNina Raben
The Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, Bethesda, Maryland, USA
Methods Enzymol 453:417-49. 2009..In this chapter, we will describe the lysosomal storage diseases in which autophagy has been explored, and present the approaches used to evaluate this essential cellular pathway... - The values and limits of an in vitro model of Pompe disease: the best laid schemes o' mice an' menShoichi Takikita
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA
Autophagy 5:729-31. 2009..The cultured myotubes, therefore, appear to be a useful model for studying the mechanisms involved in glycogen accumulation in Pompe disease and to test substrate deprivation approaches... - Deconstructing Pompe disease by analyzing single muscle fibers: to see a world in a grain of sandNina Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892 1820, USA
Autophagy 3:546-52. 2007..Clearing or preventing autophagic buildup seems, therefore, a necessary target of Pompe disease therapy... - Acid alpha-glucosidase deficiency (Pompe disease)Tokiko Fukuda
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Clinical Center, Bethesda, MD 20892, USA
Curr Neurol Neurosci Rep 7:71-7. 2007..The recombinant enzyme alglucosidase alfa is the first drug ever approved for this devastating disorder. This review discusses the benefits and the shortcomings of the new therapy... - Acid alpha-glucosidase deficiency (glycogenosis type II, Pompe disease)Nina Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Curr Mol Med 2:145-66. 2002..We will also highlight some emerging questions following the introduction of enzyme replacement therapy... - Modulation of disease severity in mice with targeted disruption of the acid alpha-glucosidase geneN Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 9N244, 9000 Rockville Pike, Bethesda, MD 20892, USA
Neuromuscul Disord 10:283-91. 2000..Females were more affected than males irrespective of genetic background. As in humans with glycogen storage disease type II, therefore, other genetic loci affect the phenotypic expression of a single gene mutation... - Detection and imaging of non-contractile inclusions and sarcomeric anomalies in skeletal muscle by second harmonic generation combined with two-photon excited fluorescenceE Ralston
Light Imaging Section, Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1535, Bethesda, MD 20892 8023, USA
J Struct Biol 162:500-8. 2008..The combination of SHG and 2PEF should be useful in the analysis and diagnosis of a wide range of skeletal muscle pathologies... - Targeted disruption of the acid alpha-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type IIN Raben
Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 273:19086-92. 1998..5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models... - Surprises of genetic engineering: a possible model of polyglucosan body diseaseN Raben
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Neurology 56:1739-45. 2001..In an attempt to accelerate the course of the disease in the knockouts, the authors increased the level of cytoplasmic glycogen by overexpressing glycogen synthase (GSase) or GlutI glucose transporter... - Enzyme replacement therapy in the mouse model of Pompe diseaseN Raben
Arthritis and Rheumatism Branch, National Institutes of Health, US HHS NIH NIAMS, 9000 Rockville Pike, Bld 10 9N244, Bethesda, MD 20892, USA
Mol Genet Metab 80:159-69. 2003..These studies suggest that enzyme replacement therapy, although at much higher doses than in other lysosomal diseases, has the potential to reverse cardiac pathology and to reduce the glycogen level in skeletal muscle... - Conditional tissue-specific expression of the acid alpha-glucosidase (GAA) gene in the GAA knockout mice: implications for therapyN Raben
Arthritis and Rheumatism Branch, NIAMS, 9000 Rockville Pike, Clinical Center Building 10 9N244, National Institutes of Health, Bethesda, MD 20892, USA
Hum Mol Genet 10:2039-47. 2001..Furthermore, using tetracycline regulation, we somatically induced human GAA in the knockout mice, and demonstrated that the skeletal and cardiac muscle pathology was completely reversible if the treatment was begun early... - Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzymeNina Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Ther 6:601-8. 2002..The results demonstrate that complete reversal of pathology in skeletal muscle or long-affected heart muscle will require much more enzyme than previously expected or a different approach... - Autophagy in skeletal muscle: implications for Pompe diseaseL Shea
The Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Int J Clin Pharmacol Ther 47:S42-7. 2009.... - Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosisJae Jin Chae
Inflammatory Biology Section, Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA
Mol Cell 11:591-604. 2003..These data support a critical role for pyrin in the innate immune response, possibly by acting on ASC, and suggest a biologic basis for the selection of hypomorphic pyrin variants in man... - The human acid alpha-glucosidase gene is a novel target of the Notch-1/Hes-1 signaling pathwayBo Yan
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892 1820, USA
J Biol Chem 277:29760-4. 2002..Constitutively over-expressed Hes-1 and Notch-1 repressed GAA gene expression. Therefore, our data establish that the human GAA gene, encoding a lysosomal enzyme, is a downstream target of the Notch-1/Hes-1 signaling pathway... - Identification and characterization of a tissue-specific silencer element in the first intron of the human acid maltase geneB Yan
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820, USA
Hum Genet 109:186-90. 2001..The data may be helpful for designing therapy to increase the level of enzyme, particularly when, as in most adults with the disease, there is reduced production of structurally normal enzyme... - Transcriptional regulation of the human acid alpha-glucosidase gene. Identification of a repressor element and its transcription factors Hes-1 and YY1B Yan
Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892-1820, USA
J Biol Chem 276:1789-93. 2001..The data should be helpful in understanding the expression and regulation of the human acid alpha-glucosidase gene as well as other lysosomal enzyme genes... - Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type IIC F Boerkoel
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, MD 20892, USA
Am J Hum Genet 56:887-97. 1995..The low level of active enzyme (12% of normal) generated from the leakage of normally spliced mRNA sustained the patient to adult life... - Quantitative evaluation of skeletal muscle defects in second harmonic generation imagesWenhua Liu
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Light Imaging Section, National Institutes of Health, Bethesda, MD 20892, USA
J Biomed Opt 18:26005. 2013..We named the software MARS (muscle assessment and rating scores). It is executed automatically and is highly sensitive even to subtle defects. We propose MARS as a powerful and unbiased tool to assess muscle health... - Glycogenosis type VII (Tarui disease) in a Swedish family: two novel mutations in muscle phosphofructokinase gene (PFK-M) resulting in intron retentionsR C Nichols
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Am J Hum Genet 59:59-65. 1996..Both mutations are predicted to result in premature termination of translation. Some of the transcripts generated from the intron 16 mutated allele also contain intron 10 sequence unspliced... - Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresisF Barbetti
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892
Diabetes 41:408-15. 1992..Two mutant alleles were identified in this patient. The allele inherited from the father had a mutation substituting alanine for Val-28; in the allele inherited from the mother, arginine was substituted for Gly-366... - Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by polF Barbetti
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
J Clin Endocrinol Metab 71:164-9. 1990..This observation is consistent with the hypothesis that the dinucleotide sequence CpG, the first two nucleotides in the arginine (CGT) codon, is a "hot spot" for mutations... - Mutations in muscle phosphofructokinase geneN Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Hum Mutat 6:1-6. 1995..Molecular diagnosis is now feasible for Ashkenazi patients who share two common mutations in the gene; the more frequent is an exon 5 splicing defect, which accounts for approximately 68% of mutant alleles in this population... - Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiencyN Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
Am J Hum Genet 56:131-41. 1995..The mutants expressed in yeast generate functional enzyme with modest changes in thermal stability. The advantages and limitations of the yeast system for expression of human mutant PFKs are discussed... - A 5' splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease)N Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
J Biol Chem 268:4963-7. 1993..Both mutations lead to inframe deletions, but of different parts of the protein. The differences between the two aberrant proteins may account for clinical differences between our patients and the Japanese patient... - Novel mutations in African American patients with glycogen storage disease Type II. Mutations in brief no. 209. OnlineN Raben
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Hum Mutat 13:83-4. 1999..The splicing defect is shared by two unrelated patients and it is linked to intragenic polymorphic sites identical to those found in patients bearing the common R854X mutation... - Common mutations in the phosphofructokinase-M gene in Ashkenazi Jewish patients with glycogenesis VII--and their population frequencyJ B Sherman
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
Am J Hum Genet 55:305-13. 1994..Because PFK deficiency in Ashkenazi Jews is caused by a limited number of mutations, screening genomic DNA from peripheral blood for the described mutations in this population should enable rapid diagnosis without muscle biopsy... - Intercellular transfer of the virally derived precursor form of acid alpha-glucosidase corrects the enzyme deficiency in inherited cardioskeletal myopathy Pompe diseaseD F Pauly
Peter Belfer Cardiac Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Hum Gene Ther 12:527-38. 2001..Taken together, these data show that the mannose 6-phosphate receptor pathway provides a useful strategy for cell-to-cell distribution of virally derived recombinant GAA... - Biochemical and pharmacological characterization of different recombinant acid alpha-glucosidase preparations evaluated for the treatment of Pompe diseaseA J McVie-Wylie
Biologics Research and Development, Genzyme Corporation, One Mountain Road, Framingham, MA 01701, USA
Mol Genet Metab 94:448-55. 2008.... - Muscle as a putative producer of acid alpha-glucosidase for glycogenosis type II gene therapyE Martin-Touaux
Département de génétique, Developpement et Pathologie Moleculaire, Institut Cochin, INSERM U567, Paris, France
Hum Mol Genet 11:1637-45. 2002..We thus demonstrate for the first time that muscle can be considered as a safe and easily accessible organ for GSD II gene therapy... - Correction of glycogen storage disease type II by enzyme replacement with a recombinant human acid maltase produced by over-expression in a CHO-DHFR(neg) cell lineF Martiniuk
Department of Medicine, Pulmonary Division and Critical Care Medicine, New York University Medical Center, New Bellevue 6N5, 550 First Avenue, New York, New York, 10016, USA
Biochem Biophys Res Commun 276:917-23. 2000..More importantly, after multiple infusions, hind, and fore-limb muscle weakness was reversed. This rhGAA would be ideal for enzyme replacement therapy in GSD II...