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Preclinical Toxicity Evaluation of AAV for Pain: Evidence from Human AAV Studies and from the Pharmacology of Analgesic Drugs
- Source :
- Molecular Pain
- Publication Year :
- 2014
- Publisher :
- SAGE Publications, 2014.
-
Abstract
- Gene therapy with adeno-associated virus (AAV) has advanced in the last few years from promising results in animal models to >100 clinical trials (reported or under way). While vector availability was a substantial hurdle a decade ago, innovative new production methods now routinely match the scale of AAV doses required for clinical testing. These advances may become relevant to translational research in the chronic pain field. AAV for pain targeting the peripheral nervous system was proven to be efficacious in rodent models several years ago, but has not yet been tested in humans. The present review addresses the steps needed for translation of AAV for pain from the bench to the bedside focusing on pre-clinical toxicology. We break the potential toxicities into three conceptual categories of risk: First, risks related to the delivery procedure used to administer the vector. Second, risks related to AAV biology, i.e., effects of the vector itself that may occur independently of the transgene. Third, risks related to the effects of the therapeutic transgene. To identify potential toxicities, we consulted the existing evidence from AAV gene therapy for other nervous system disorders (animal toxicology and human studies) and from the clinical pharmacology of conventional analgesic drugs. Thereby, we identified required preclinical studies and charted a hypothetical path towards a future phase I/II clinical trial in the oncology-palliative care setting.
- Subjects :
- medicine.medical_specialty
Neurology
Pain medicine
Genetic enhancement
Genetic Vectors
Drug Evaluation, Preclinical
Pain
Translational research
Review
Pharmacology
Toxicology
medicine.disease_cause
law.invention
Cellular and Molecular Neuroscience
Gene therapy
Adeno-associated virus
law
Animals
Humans
Pain Management
Medicine
Analgesics
Clinical pharmacology
business.industry
Chronic pain
Genetic Therapy
medicine.disease
Interleukin-10
Clinical trial
Beta-endorphin
Anesthesiology and Pain Medicine
Satellite Viruses
Molecular Medicine
business
Subjects
Details
- ISSN :
- 17448069
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Molecular Pain
- Accession number :
- edsair.doi.dedup.....22251b6d4b4c98fc95c5bd32afda39d0