Abstract
Significant advances in therapy for lysosomal storage disorders have occurred with an accelerating pace over the past decade. Although enzyme replacement therapy has improved the outcome of lysosomal storage disorders, antibody responses have occurred and sometimes prevented efficacy, especially in cross-reacting immune material negative patients with Pompe disease. Preclinical gene therapy experiments have revealed the relevance of immune responses to long-term efficacy. The choice of regulatory cassette played a critical role in evading humoral and cellular immune responses to gene therapy in knockout mouse models, at least in adult animals. Liver-specific regulatory cassettes prevented antibody formation and enhanced the efficacy of gene therapy. Regulatory T cells prevented transgene directed immune responses, as shown by adoptive transfer of antigen-specific immune tolerance to enzyme therapy. Immunomodulatory gene therapy with a very low vector dose could enhance the efficacy of enzyme therapy in Pompe disease and other lysosomal storage disorders.
Keywords: Pompe disease, Gaucher disease, Niemann pick disease, Fabry disease, gene therapy, enzyme replacement therapy, immune tolerance, neutralizing antibodies, inhibitory antibodies, glycogen
Current Gene Therapy
Title: Immunomodulatory Gene Therapy in Lysosomal Storage Disorders
Volume: 9 Issue: 6
Author(s): Dwight D. Koeberl and Priya S. Kishnani
Affiliation:
Keywords: Pompe disease, Gaucher disease, Niemann pick disease, Fabry disease, gene therapy, enzyme replacement therapy, immune tolerance, neutralizing antibodies, inhibitory antibodies, glycogen
Abstract: Significant advances in therapy for lysosomal storage disorders have occurred with an accelerating pace over the past decade. Although enzyme replacement therapy has improved the outcome of lysosomal storage disorders, antibody responses have occurred and sometimes prevented efficacy, especially in cross-reacting immune material negative patients with Pompe disease. Preclinical gene therapy experiments have revealed the relevance of immune responses to long-term efficacy. The choice of regulatory cassette played a critical role in evading humoral and cellular immune responses to gene therapy in knockout mouse models, at least in adult animals. Liver-specific regulatory cassettes prevented antibody formation and enhanced the efficacy of gene therapy. Regulatory T cells prevented transgene directed immune responses, as shown by adoptive transfer of antigen-specific immune tolerance to enzyme therapy. Immunomodulatory gene therapy with a very low vector dose could enhance the efficacy of enzyme therapy in Pompe disease and other lysosomal storage disorders.
Export Options
About this article
Cite this article as:
Koeberl D. Dwight and Kishnani S. Priya, Immunomodulatory Gene Therapy in Lysosomal Storage Disorders, Current Gene Therapy 2009; 9 (6) . https://dx.doi.org/10.2174/156652309790031094
DOI https://dx.doi.org/10.2174/156652309790031094 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Advances in CAR-T Cell Therapy and CRISP combination
CAR-T cell therapy is a groundbreaking immunotherapy that has transformed cancer treatment, particularly in hematological malignancies like leukemia and lymphoma. It involves engineering a patient’s own T cells to express chimeric antigen receptors (CARs) that target and destroy cancer cells. The therapy has demonstrated remarkable success, achieving durable remissions in ...read more
Melatonin Signaling in Health and Disease
Melatonin regulates a multitude of physiological functions, including circadian rhythms, acting as a scavenger of free radicals, an anti-inflammatory agent, a modulator of mitochondrial homeostasis, an antioxidant, and an enhancer of nitric oxide bioavailability. AANAT is the rate-limiting enzyme responsible for converting serotonin to NAS, which is further converted to ...read more
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers.
Programmed cell death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
The now and future of gene transfer technologies
Gene and cell therapies rely on a gene delivery system which is safe and effective. Both viral and non-viral vector systems are available with specific pros and cons. The choice of a vector system is largely dependent on the application which is a balance between target tissue/disease and safety, efficacy ...read more
Related Journals

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
- Announcements
Related Articles
-
Beyond Ejection Fraction: Novel Clinical Approaches Towards Sudden
Cardiac Death Risk Stratification in Patients with Dilated Cardiomyopathy
Current Cardiology Reviews Re-Wiring the Circuit: Mitochondria as a Pharmacological Target in Liver Disease
Current Medicinal Chemistry Expression and Functions of Heat Shock Proteins in the Normal and Pathological Mammalian Eye
Current Molecular Medicine CD36 and Intestinal Fatty Acid Absorption
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Understanding the Molecular Aspects of Vitamins in Parkinson’s Disease: Present-day Concepts and Perspectives
Current Pharmaceutical Design Humoral Immunity in Heart Failure
Cardiovascular & Hematological Disorders-Drug Targets The Diagnostic and Prognostic Value of Brain Natriuretic Peptide and Aminoterminal (nt)-pro Brain Natriuretic Peptide
Current Pharmaceutical Design Heart Failure in Sub-Saharan Africa
Current Cardiology Reviews Safety and Efficacy of Adenovirus Carrying Hepatocyte Growth Factor Gene by Percutaneous Endocardial Injection for Treating Post-infarct Heart Failure: A Phase IIa Clinical Trial
Current Gene Therapy Targeting microRNAs in Pathological Hypertrophy and Cardiac Failure
Mini-Reviews in Medicinal Chemistry Urinary Steroids Measured by Modern Separation Techniques and Applied as Biomarkers in Stress Studies
Current Pharmaceutical Analysis Mitochondria Damage in the Pathogenesis of Diabetic Retinopathy and in the Metabolic Memory Associated with its Continued Progression
Current Medicinal Chemistry Water Soluble Vitamins and their Role in Diabetes and its Complications
Current Diabetes Reviews New Insights into HLA-G and Inflammatory Diseases
Inflammation & Allergy - Drug Targets (Discontinued) The Therapeutic Potential of Hepatocyte Growth Factor for Myocardial Infarction and Heart Failure
Current Pharmaceutical Design Lifestyle Interventions for Cardiovascular Risk Reduction in Women with Breast Cancer
Current Cardiology Reviews Pharmacological Targeting in Inherited Arrhythmia Syndromes
Current Medicinal Chemistry Treatment with Cannabidiol Results in an Antioxidant and Cardioprotective Effect in Several Pathophysiologies
Current Hypertension Reviews PARADIGM - HF: The Rise of the Arnis
Reviews on Recent Clinical Trials Electrocardiographic and Cardiac Autonomic Indices - Implications of Sex-Specific Risk Stratification in Women After Acute Myocardial Infarction
Current Pharmaceutical Design