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Development of a novel therapy for epidermolysis bullosa using recombinant

Research Project

Project/Area Number 13357008
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Dermatology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

SHIMIZU Hiroshi  Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (00146672)

Co-Investigator(Kenkyū-buntansha) FURUICHI Yasuhiro  GeneCare Research Institute Co.Ltd., Manager, 所長(研究職)
SHIMIZU Tadamichi  Hokkaido University, Hospital, Lec., 医学部・歯学部附属病院, 講師 (70260396)
SAWAMURA Daisuke  Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (60196334)
MASUNAGA Takuji  KOSE Corporation, Chief Researcher, 主任研究員
松村 和子  北海道大学, 医学部附属大学, 助手 (10311515)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥48,490,000 (Direct Cost: ¥37,300,000、Indirect Cost: ¥11,190,000)
Fiscal Year 2003: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2002: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2001: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
KeywordsWound healing / epidermolysis bullosa / dystrophic / severe type / type VII collagen / protein supplement / gene therapy / epidermal transplantation / 表皮水疱症 / 表皮 / 基底膜 / ラミニン5 / 培養表皮シート / 補充治療 / クローニング / 補充療法
Research Abstract

Epidermolysis bullosa consists of a group of genetically determined skin disorders where minor trauma causes blisters and erosions in the skin and mucous membranes. Recent advance in epidermolysis bullosa research has identified several causative genes which encoding structural proteins for stability in adhesion of the epidermis and the dermis. However, there is no effective treatment for epidermolysis bullosa.
The purposes of this study are to make a precise diagnosis of the patients with epidermolysis bullosa and to develop a protein therapy based on novel strategy, in which we produce defective recombinant protein and provide it to skin lesions of the patients.
In this study we performed mutation analysis of many patients in Japan as well as foreign countries. Also, we treated patients with autologous epidermal sheet graft in Hokkaido University. Furthermore, we succeeded in purification of recombinant type VII collagen which majority of severe patients with epidermolysis bullosa lack in Japan.
In this study, our mutation analysis of epidermolysis bullosa resulted in disclosing new findings about epidermolysis bullosa diagnostic and pathophysiological aspects. Although protein therapies using recombinant enzymes are ongoing in clinical practice, those using structural proteins has been never tried before. This study provide a great potential of protein therapy in the future.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (70 results)

All Other

All Publications (70 results)

  • [Publications] Arita K, et al.: "Squamous cell carcinoma in a patien with non-bullous congenital ichthyosiform erythroderma."Br J Dermatol. 148. 363-384 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu T, et al.: "Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor (MIF) : Its potential anti-inflammatory action."Clin Exp Allergy. 34. 103-109 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuzaki Y, et al.: "Keratinocyte responsive element 3 : analysis of a keratinocyte-specific regulatory sequence in the 230 kDa bullous pemphigoid antigen promoter."J Invest Dermatol. 120. 308-312 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawamura D, et al.: "Identification of COL7A1 alternative splicing inserting 9 amino acid residues into the fibronectin type III linker domain."J Invest Dermatol. 120. 942-948 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawamura D, et al.: "Epidermolysis bullosa : directions for future research and new challenges for treatment."Arch Dermatol Res. 295 Suppl 1. S34-S42 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawasaki H, et al.: "Squamous cell carcinoma developing in a 12-year-old boy with non Hallopeau-Siemens recessive dystrophic epidermolysis bullosa."Br J Dermatol. 148. 1047-1050 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Liu Y, et al.: "Immunofluorescence studies using skin sections of recessive dystrophic epidermolysis bullosa patients indicated that the antigen of anti-p200 pemphigoid is not a fragment of type VII collagen."J Dermatol Sci. 32. 125-129 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Epidermal basement membrane zone components : ultrastructural distribution and molecular interactions."J Dermatol Sci. 31. 169-177 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Ultrastructural orientation of laminin 5 in the epidermal basement membrane : an updated model for basement membrane organization."J Histochem Cytochem. 51. 1299-1306 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Alterations in desmosome size and number coincide with the loss of keratinocyte cohesion in skin with homozygous and heterozygous defects in the desmosomal protein plakophilin 1."J Invest Dermatol. 121. 96-103 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Immunomapping of EBA sera to multiple epitopes on collagen VII : further evidence that anchoring fibrils originate and terminate in the lamina densa."Exp Dermatol. 12. 261-267 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Siegel DH, et al.: "Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome."Am J Hum Genet. 73. 174-187 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomita Y, et al.: "Simultaneous occurrence of three squamous cell carcinomas in a recessive dystrophic epidermolysis bullosa patient."Acta Derm Venereol. 83. 225-226 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuji Y, et al.: "Changing pattern of deiminated proteins in developing human epidermis."J Invest Dermatol. 120. 817-822 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuyama N, et al.: "The dinucleotide microsatellite polymorphism of the IFNAR1 gene promoter correlates with responsiveness of hepatitis C patients to interferon."Hepatol Res. 25. 221-225 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh M, et al.: "Innate apoptosis of human B lymphoblasts transformed by Epstein-Barr virus : modulation by cellular immortalization and senescence."Cell Struct Funct. 28. 61-70 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akiyama M, et al.: "Truncation of CGI-58 Protein Causes Malformation of Lamellar Granules Resulting in Ichthyosis in Dorfman-Chanarin Syndrome."J Invest Dermatol. 121. 1029-1034 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arita K, et al.: "Severely hyperkeratotic erythroderma associated with Hodgkin's disease - Dose high serum G-CSF contribute to the formation of skin lesions?"J Am Acad Dermatol. 49. 772-773 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki H, et al.: "A novel Sp1-family-related cis-acting element for transcription of type VII collagen gene (COL7A1)."J Dermatol Sci. 32. 239-242 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato-Matsumura KC, et al.: "A novel insertion mutation in COL7A1 identified in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa."Acta Dermato-Venereol. 83. 137-138 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arita K, et al.: "Squamous cell carcinoma in a patien with non-bullous congenital ichthyosiform erythroderma."Br J Dermatol. 148. 363-384 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu T, et al.: "Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor (MIF) : Its potential anti-inflammatory action."Clin Exp Allergy. 34. 103-109 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuzaki Y, et al.: "Keratinocyte responsive element 3 : analysis of a keratinocyte-specific regulatory sequence in the 230 kDa bullous pemhigoid antigen promoter"J Invest Dermatol. 120. 308-312 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawamura D, et al.: "Identification of COL7A1 alternative splicing inserting 9 amino acid residues into the fibronectin type III linker domain."J Invest Dermatol. 120. 942-948 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawamura D, et al.: "Epidermolysis bullosa : directions for future research and new challenges for treatment."Arch Dermatol Res. 295 Suppl 1. S34-S42 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawasaki H, et al.: "Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa."Br J Dermatol. 148. 1047-1050 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Liu Y, et al.: "Immunofluorescence studies using skin sections of recessive dystrophic epidermolysis bullosa patients indicated that the antigen of anti-p200 pemphigoid is not a fragment of type VII collagen."J Dermatol Sci. 32. 125-129 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Epidermal basement membrane zone components : ultrastructural distribution and molecular interactions."J Dermatol Sci. 31. 169-177 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Ultarastructural orientation of laminin 5 in the epidermal basement membrane : an updated model for basement membrane organization."J Histochem Cytochem. 51. 1299-1306 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Alterations in desmosome size and number coincide with the loss of keratinocyte cohesion in skin with homozygous and heterozygous defects in the desmosomal protein plakophilin 1."J Invest Dermatol. 121. 96-103 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] McMillan JR, et al.: "Immunomapping of EBA sera to multiple epitopes on collagen VII : further evidence that anchoring fibrils originate and terminate in the lamina densa."Exp Dermatol. 12. 261-267

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Siegel DH, et al.: "Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome."Am J Hum Genet. 73. 174-187 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomita Y, et al.: "Simultaneous occurrence of three squamous cell carcinomas in a recessive dystroplic epidermolysis bullosa patient."Acta Derm Venereol. 83. 2225-226

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuji Y, et al.: "Changing pattern of deiminated proteins in developing human epidermis."J Invest Dermatol. 120. 817-822 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuyama N, et al.: "The dinucleotide microsatelliste polymorphism of the IFNAR1 gene promoter correlates with responsiveness of hepatitis C patients to interferon."Hepatol Res. 25. 221-225

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh M, et al.: "Innate apoptosis of human B lymphoblasts transformed by Epstein-Barr virus : modulation by cellular immortalization and senescence."Cell Struct Funct. 28. 61-70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akiyama M, et al.: "Truncation of CGI-58 Protein Causes Malformation of Lamellar Granules Resulting in Ichthyosis in Dorfman-Chanarin Syndrome."J Invest Dermatol. 121. 1029-1034 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arita K, et al.: "Severely hyperkeratotic erythroderma associated with Hogkin's diseas-Dose high serum G-CSF contribute to the formation of skin lesions?"J Am Acad Dermatol. 49. 772-773

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki H, et al.: "A novel Spl-family-related cis-acting element for transcription of type VII collagen gene (COL7A1)"J Dermaol Sci. 32. 239-242

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato-Matsumura KC, et al.: "A novel insertion mutation in COL7A1 identified in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa"Acta Dermato-Venereol. 83. 137-138

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arita K, et al.: "Squamous cell carcinoma in a patien with non-bullous congenital ichthyosiform erythroderma"Br J Dermatol. 148. 363-384 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu T, et al.: "Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor (MIF) : Its potential anti-inflammatory action"Clin Exp Allergy. 34. 103-109 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuzaki Y, et al.: "Keratinocyte responsive element 3 : analysis of a keratinocyte-specific regulatory sequence in the 230 kDa bullous pemhigoid antigen promoter"J Invest Dermatol. 120. 308-312 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sawamura D, et al.: "Identification of COL7A1 alternative splicing inserting 9 amino acid residues into the fibronectin type III linker domain"J Invest Dermatol. 120. 942-948 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sawamura D, et al.: "Epidermolysis bullosa : directions for future research and new challenges for treatment"Arch Dermatol Res. 295 Suppl 1. S34-S42 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawasaki H, et al.: "Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa"Br J Dermatol. 148. 1047-1050 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Liu Y, et al.: "Immunofluorescence studies using skin sections of recessive dystrophic epidermolysis bullosa patients indicated that the antigen of anti-p200 pemphigoid is not fragment of type VII collagen"J Dermatol Sci. 32. 125-129 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] McMillan JR, et al.: "Epidermal basement membrane zone components : ultrastructural distribution and molecular interactions"J Dermatol Sci. 31. 169-177 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] McMillan JR, et al.: "Ultarastructural orientation of laminin 5 in the epidermal basement membrane : an undated model for basement membrane organization"J Histochem Cytochem. 51. 1299-1306 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] McMillan JR, et al.: "Alterations in desmosome size and number coincide with the loss of keratinocyte cohesion in skin with homozygous and heterozygous defects in the desmosomal protein plakophilin 1"J Invest Dermatol. 121. 96-103 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] McMillan JR, et al.: "Immunomapping of EBA sera to multiple epitopes on collagen VII further evidence that anchoring fibrils originate and terminate in the lamina densa"Exp Dermatol. 12. 261-267 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Siegel DH, et al.: "Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome"Am J Hum Genet. 73. 174-187 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomita Y, et al.: "Simultaneous occurrence of three squamous cell carcinomas in a recessive dystrophic epidermolysis bullosa patient"Acta Derm Venereol. 83. 225-226 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuji Y, et al.: "Changing pattern of deiminated proteins in developing human epidermis"J Invest Dermatol. 120. 817-822 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuyama N, et al.: "The dinucleotide microsatellite polymorphism of the IFNARI gene promoter correlates with responsiveness of hepatitis C patients to interferon"Hepatol Res. 25. 221-225 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Satoh M, et al.: "Innate apoptosis of human B lymphoblasts transformed by Epstein-Barr virus : modulation by cellular immortalization and senescence"Cell Struct Funct. 28. 61-70 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akiyama M, et al.: "Truncation of CGI-58 Protein Causes Malformation of Lamellar Granules Resulting in Ichthyosis in Dorfman-Chanarin Syndrome"J Invest Dermatol. 121. 1029-1034 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arita K, et al.: "Severely hyperkeratotic erythroderma associated with Hogkin's diseas-Dose high serum G-CSFcontribute to the formation of skin lesions?"J Am Acad Dermatol. 49. 772-773 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sasaki H, et al.: "A novel Sp 1-family-related cis-acting element for transcription of type VII collagen gene (COL7A1)"J Dermaol Sci. 32. 239-242 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato-Matsumura KC, et al.: "A novel insertion mutation in COL7A1 identified in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa"Acta Dermato-Venereol. 83. 137-138 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato-Matsumura KC, et al.: "Toenail dystrophy with COL7A1 glycine substitution mutations segregates as an autosomal dominant trait in 2 families with dystrophic epidermolysis bullosa"Arch Dermatol. 138. 269-271 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sawamura D, et al.: "Direct injection of naked DNA and cytokine transgene expression : implications for keratinocyte gene therapy"Clin Exp Dermatol. 27. 480-484 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sawamura D, et al.: "The majority of keratinocytes incorporate intradermally injected plasmid DNA regardless of size but only a small proportion of cells can express the gene product"J Invest Dermatol. 118. 967-971 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasukawa K, et al.: "Exclusion of COL7A1 mutation in Kindler syndrome"J Am Acad Dermatol. 46. 447-450 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasukawa K, et al.: "Dominant and recessive compound heterozygous mutations in epidermolysis bullosa simplex demonstrate the role of the stutter region in keratin intermediate filament assembly"J Biol Chem. 277. 23670-23674 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishiko A, et al.: "A novel leucine to valine mutation in residue 7 of the helix initiation motif of keratin10 leads to bullous congenital ichthyosiform erythroderma"J Invest Dermatol. 116. 991-992 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasukawa K, et al.: "Kikuchi's disease and the skin: case report and review of the literature"Br J Dermatol. 144. 885-889 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimizu T, et al.: "High macrophage migration inhibitory factor (MIF) serum levels associated with extended psoriasis"J Invest Dermatol. 116. 989-990 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akiyama M, et al.: "Compound heterozygous TGM1 mutations including a novel missense mutation L204Q in a mild form of lamellar ichthyosis"J Invest Dermatol. 116. 992-995 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akiyama M, et al.: "Novel mutations of TGM1 in a child with congenital ichthyosiform erythroderma"Br J Dermatol. 144. 401-407 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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