Abstract
Genetic mutations affecting the capacity of basal keratinocytes to adhere firmly to the underneath derma lead to severe, often lethal, blistering disorders of the skin known as Epidermolysis Bullosa (EB). About 400000-500000 people worldwide are affected and no definitive treatments have yet been developed. Gene therapy might represent an alternative therapeutic approach for these devastating inherited disorders. In the last 10 years pre-clinical studies have shown that human epidermal stem cells can be stably transduced using integrating vectors allowing long-term genetic correction of the adhesion defects affecting EB keratinocytes both in vitro and in vivo after transplantation onto immunodeficient animals. In addition tremendous progress have been achieved in the clinical applications of cultured keratinocytes (cell therapy) for the regeneration of the epidermis over full thickness wounds or the restoration of damaged corneal surfaces. The combination of (i) optimised culturing conditions not altering the epidermal stemness, (ii) gene transfer vectors able to target epidermal stem cells very efficiently and (iii) surgical procedures allowing the grafting of large skin areas have therefore led our group to submit the first phase I/II gene therapy clinical trial for Junctional Epidermolysis Bullosa.
Keywords: Epidermolysis bullosa, Gene therapy, Keratinocyte, Stem cells
Reviews on Recent Clinical Trials
Title: Towards a Gene Therapy Clinical Trial for Epidermolysis Bullosa
Volume: 1 Issue: 2
Author(s): Ferrari Stefano, Pellegrini Graziella, Matsui Tatsuya, Mavilio Fulvio and De L. Michele
Affiliation:
Keywords: Epidermolysis bullosa, Gene therapy, Keratinocyte, Stem cells
Abstract: Genetic mutations affecting the capacity of basal keratinocytes to adhere firmly to the underneath derma lead to severe, often lethal, blistering disorders of the skin known as Epidermolysis Bullosa (EB). About 400000-500000 people worldwide are affected and no definitive treatments have yet been developed. Gene therapy might represent an alternative therapeutic approach for these devastating inherited disorders. In the last 10 years pre-clinical studies have shown that human epidermal stem cells can be stably transduced using integrating vectors allowing long-term genetic correction of the adhesion defects affecting EB keratinocytes both in vitro and in vivo after transplantation onto immunodeficient animals. In addition tremendous progress have been achieved in the clinical applications of cultured keratinocytes (cell therapy) for the regeneration of the epidermis over full thickness wounds or the restoration of damaged corneal surfaces. The combination of (i) optimised culturing conditions not altering the epidermal stemness, (ii) gene transfer vectors able to target epidermal stem cells very efficiently and (iii) surgical procedures allowing the grafting of large skin areas have therefore led our group to submit the first phase I/II gene therapy clinical trial for Junctional Epidermolysis Bullosa.
Export Options
About this article
Cite this article as:
Stefano Ferrari, Graziella Pellegrini, Tatsuya Matsui, Fulvio Mavilio and Michele L. De, Towards a Gene Therapy Clinical Trial for Epidermolysis Bullosa, Reviews on Recent Clinical Trials 2006; 1 (2) . https://dx.doi.org/10.2174/157488706776876472
DOI https://dx.doi.org/10.2174/157488706776876472 |
Print ISSN 1574-8871 |
Publisher Name Bentham Science Publisher |
Online ISSN 1876-1038 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Panobinostat: The Small Molecule Metalloenzyme Inhibitor with Marvelous Anticancer Activity
Current Topics in Medicinal Chemistry Strategies for Overcoming Inherent and Acquired Resistance to EGFR Inhibitors by Targeting Downstream Effectors in the RAS/PI3K Pathway
Current Cancer Drug Targets Cyclin-Dependent Kinase Inhibitors as Anticancer Drugs
Current Drug Targets Microarrays and Colon Cancer in the Road for Translational Medicine
Current Bioinformatics The Stable Isotope Use in the Exploration of Bioavailability and Metabolism of Magnesium
Current Nutrition & Food Science Bone Metastasis: Molecular Mechanisms Implicated in Tumour Cell Dormancy in Breast and Prostate Cancer
Current Cancer Drug Targets Strategies for the Biological Evaluation of Gold Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Fighting Tumor Cell Survival: Advances in the Design and Evaluation of Pim Inhibitors
Current Medicinal Chemistry Targeted Therapy Towards Cancer-A Perspective
Anti-Cancer Agents in Medicinal Chemistry The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Current Cancer Drug Targets Patenting Human Genes and Stem Cells
Recent Patents on DNA & Gene Sequences Anti-Apoptotic Mechanisms of Drug Resistance in Cancer
Current Cancer Drug Targets CDK-associated Cullin 1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Human Glioblastoma
Current Cancer Drug Targets Gene Transfer to the Central Nervous System: Current State of the Art of the Viral Vectors
Current Genomics Selective Chemokine Receptor-Targeted Depletion of Pathological Cells as A Therapeutic Strategy for Inflammatory, Allergic and Autoimmune Diseases
Recent Patents on Inflammation & Allergy Drug Discovery P-Glycoprotein Mediated Multidrug Resistance Reversal by Phytochemicals: A Review of SAR & Future Perspective for Drug Design
Current Topics in Medicinal Chemistry Alzheimers Disease: From Pathogenesis to Disease-Modifying Approaches
CNS & Neurological Disorders - Drug Targets Surface Plasmon Resonance Imaging (SPRI) Sensor for Cystatin Determination Based on Immobilized Papain
Protein & Peptide Letters Immunity to Tumour Antigens
Current Pharmaceutical Design Epigenetic Alterations of the Wnt/β -Catenin Pathway in Human Disease
Endocrine, Metabolic & Immune Disorders - Drug Targets