Intrathecal gene transfer by adeno-associated virus for pain

Andreas S Beutler, Michaela S. Banck, Christopher E. Walsh, Erin D. Milligan

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Chronic pain is among the most prevalent medical problems, affecting more than half of patients with advanced cancer and many with other common diseases. Current analgesics often fail to provide satisfactory symptom relief and frequently cause severe side effects. Intrathecal (IT) gene transfer is an attractive method for pain research in rodent models, because it allows targeting of a wide variety of secretable peptides and proteins to the spinal cord, an important neural center for the processing of nociceptive signals. The potential of IT gene transfer for improving opioid therapy and for validating new analgesic targets, such as cytokines involved in spinal glial activation, is discussed. The IT space has been notoriously resistant to efficient gene transfer, limiting therapeutic gene expression to less than 2 weeks with most vector systems. Recent progress with adeno-associated virus (AAV) technology allowed efficient long-term gene expression, facilitating studies reflective of the chronic nature of many pain states. AAV is one of the most advanced gene therapy vectors currently undergoing clinical trials for a variety of disorders. In patients, AAV vectors could be administered intrathecally by a lumbar puncture, a safe procedure routinely performed at the bedside. AAV vectors may therefore become an important tool for translational studies to validate newly identified therapeutic targets in clinical pain states.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalCurrent Opinion in Molecular Therapeutics
Volume7
Issue number5
StatePublished - Oct 2005
Externally publishedYes

Fingerprint

Dependovirus
Pain
Genes
Analgesics
Gene Expression
Spinal Puncture
Neuroglia
Chronic Pain
Genetic Therapy
Opioid Analgesics
Rodentia
Spinal Cord
Therapeutics
Clinical Trials
Cytokines
Technology
Peptides
Research
Neoplasms
Proteins

Keywords

  • β-endorphin
  • Adeno-associated virus
  • Chronic pain
  • Gene therapy
  • Glial activation
  • Interleukin-10
  • Intrathecal
  • Spinal cord

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Intrathecal gene transfer by adeno-associated virus for pain. / Beutler, Andreas S; Banck, Michaela S.; Walsh, Christopher E.; Milligan, Erin D.

In: Current Opinion in Molecular Therapeutics, Vol. 7, No. 5, 10.2005, p. 431-439.

Research output: Contribution to journalArticle

Beutler, AS, Banck, MS, Walsh, CE & Milligan, ED 2005, 'Intrathecal gene transfer by adeno-associated virus for pain', Current Opinion in Molecular Therapeutics, vol. 7, no. 5, pp. 431-439.
Beutler, Andreas S ; Banck, Michaela S. ; Walsh, Christopher E. ; Milligan, Erin D. / Intrathecal gene transfer by adeno-associated virus for pain. In: Current Opinion in Molecular Therapeutics. 2005 ; Vol. 7, No. 5. pp. 431-439.
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