Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain

Adenovirus-mediated gene transfer of interferon gamma (AdlFN) elicits rejec tion of intracerebral Lewis lung carcinoma. In this system, gene transfer i nto brain parenchymal cells is both necessary and sufficient to generate th e antitumor response. Despite persistent parenchymal inflammation and demye lination, wild-type mice injected intracerebrally with either AdlFN or beta -galactosidase adenovirus (AdBGAL) perform as well as non-injected animals in behavioral, memory, and motor tests. Both AdlFN and AdBGAL elicit demye lination whose incidence rises sharply when the lowest effective dose of Ad lFN is exceeded. Therefore, transfer of interferon gamma into brain parench yma does not seem to elicit detectable cognitive, behavioral or motor defic its. Furthermore, gene transfer into the brain, by adenoviral vectors curre ntly in clinical trials, is associated with a narrow therapeutic window whe re the incidence of demyelination rises sharply soon after the effective do se is achieved.