A paracrine paradigm for in vivo gene therapy in the central nervous system: Treatment of chronic pain

A limitation of current gene therapy efforts aimed at central nervous syste m disorders concerns distribution of vectors on direct injection into neura l tissue. Here we have circumvented this problem by transferring genes to t he meninges surrounding the spinal cord, achieving an in vivo gene transfer paradigm for treating chronic pain. The therapeutic vector consisted of a recombinant adenovirus encoding a secreted form of the potent endogenous op ioid beta-endorphin. In an inflammation model of persistent pain, administr ation of the vector into the cerebrospinal fluid (CSF) surrounding the spin al cord transduced meningeal pia mater cells. The resulting increase in bet a-endorphin secretion attenuated inflammatory hyperalgesia, yet had no effe ct on basal nociceptive responses. This demonstration of a gene transfer ap proach to pain treatment can be generalized to neurodegenerative disorcers in which broad spatial distribution of therapeutic effect is critical.