Influence of the Immune System on Central Nervous System Gene Transfer

Forsayeth, John

doi:10.1016/b978-012397632-1/50005-8

Cited by 3 publications

(3 citation statements)

References 47 publications

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“…Moreover, before treatments can be brought to the clinic, not only the efficacy, but also the safety of the treatment must be carefully addressed and evaluated using clinically relevant experimental models. Important considerations include immune reactions, which may be triggered by the immunogenicity of the transgene product or by the vector serotypes or the transplanted cells [41]. In this respect, both adaptive immunity and innate immunity mechanisms should be explored since the production of inflammatory mediators by glia, neurons and endothelial cells in the target brain area may prime seizures and neuronal cell loss [42,43].…”

Section: Five-year Viewmentioning

confidence: 99%

The promise of gene therapy for the treatment of epilepsy

Vezzani

2007

Expert Review of Neurotherapeutics

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Gene therapy involves the transfer and expression of a therapeutic gene into a target tissue, and essentially represents an intervention that alters the instruction set of a cell having a dominant effect on the cell phenotype. Gene therapy techniques may provide a realistic therapeutic option for CNS disorders that are difficult to treat with conventional drugs, such as for drug-resistant focal epilepsies. Preclinical studies using a selection of 'therapeutic' genes delivered into the rodent brain showed significant reduction of seizures and inhibition of epileptogenesis, thus establishing the proof-of-principle evidence of the potential applicability of this technology to human epilepsy. The promising potential of gene therapy for the treatment of CNS pathologies still requires further investigation to improve the efficacy and the safety of this approach using clinically relevant experimental models. The recent advances in refining gene therapy tools and in methods of gene delivery make this innovative approach a definite possibility for therapeutic intervention.

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Section: Five-year Viewmentioning

confidence: 99%

The promise of gene therapy for the treatment of epilepsy

Vezzani

2007

Expert Review of Neurotherapeutics

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“…While the AAV2 vector can provoke, under some circumstances, a mild humoral response, especially when the vector escapes from the brain into the peripheral circulation, the immune response is typically directed against capsid proteins rather than the encoded transgene. The issues concerning AAV immunology has been reviewed much more thoroughly elsewhere and the interested reader is directed to more in-depth discussions [51,52]. The second advantage of the AAV2 vector is historical.…”

Section: A Neurotherapeutic Framework For Pdmentioning

confidence: 99%

Gene Therapy for the Treatment of Parkinson’s Disease: The Nature of the Biologics Expands the Future Indications

2012

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The pharmaceutical industry’s development of therapeutic medications for the treatment of Parkinson’s disease (PD) endures, as a result of the continuing need for better agents, and the increased clinical demand due to the aging population. Each new drug offers advantages and disadvantages to patients when compared to other medical offerings or surgical options. Deep brain stimulation (DBS) has become a standard surgical remedy for the effective treatment of select patients with PD, for whom most drug regimens have failed or become refractory. Similar to DBS as a surgical option, gene therapy for the treatment of PD is evolving as a future option. In the four different PD gene therapy approaches that have reached clinical trials investigators have documented an excellent safety profile associated with the stereotactic delivery, viral vectors and doses utilized, and transgenes expressed. In this article, we review the clinically relevant gene therapy strategies for the treatment of PD, concentrating on the published preclinical and clinical results, and the likely mechanisms involved. Based on these presentations, we advance an analysis of how the nature of the gene therapy used may eventually expand the scope and utility for the management of PD.

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“…Little or no detectable innate immune response has been described after injecting AAV2 into rat brain [32,33] with only a modest transient astrocytic activation at the injection site [34]. Injection of AAV2 into rat brain, however, generates a humoral anti-capsid immunity that depends on vector dose [35,36]. Moreover, high titers of existing anti-AAV2 capsid antibody produced by prior peripheral immunization blocked transduction of rat striatum by AAV2-human amino acid decarboxylase (hAADC), but did not trigger any cell-mediated response and did not eliminate already transduced striatal neurons [36].…”

Section: Immunologic Responsementioning

confidence: 99%

Gene Therapy for Misfolding Protein Diseases of the Central Nervous System

et al. 2013

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Protein aggregation as a result of misfolding is a common theme underlying neurodegenerative diseases. Accordingly, most recent studies aim to prevent protein misfolding and/or aggregation as a strategy to treat these pathologies. For instance, state-of-the-art approaches, such as silencing protein overexpression by means of RNA interference, are being tested with positive outcomes in preclinical models of animals overexpressing the corresponding protein. Therapies designed to treat central nervous system diseases should provide accurate delivery of the therapeutic agent and long-term or chronic expression by means of a nontoxic delivery vehicle. After several years of technical advances and optimization, gene therapy emerges as a promising approach able to fulfill those requirements. In this review we will summarize the latest improvements achieved in gene therapy for central nervous system diseases associated with protein misfolding (e.g., amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, Huntington's, and prion diseases), as well as the most recent approaches in this field to treat these pathologies.

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Influence of the Immune System on Central Nervous System Gene Transfer

Cited by 3 publications

References 47 publications

The promise of gene therapy for the treatment of epilepsy

The promise of gene therapy for the treatment of epilepsy

Gene Therapy for the Treatment of Parkinson’s Disease: The Nature of the Biologics Expands the Future Indications

Gene Therapy for Misfolding Protein Diseases of the Central Nervous System

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