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The development of improved gene transfer vectors has been hampered by the lack of a nonimmunogenic reporter gene that can be serially quantified in the serum or from other sites. In response to the need to develop a new reporter protein, we have evaluated alpha-fetoprotein (AFP) as a potential candidate. A first-generation E1/E3-deleted adenoviral vector expressing human AFP (hAFP) was generated as a preliminary tool to evaluate AFP as a reporter. Using both mouse and baboon models, hAFP expression was evaluated in serum after intravenous delivery and in serum and bronchioalveolar lavage (BAL) fluid after delivery to the lung. In immunocompetent animals, intravenous delivery of the hAFP adenoviral vector resulted in hAFP expression in the serum early after injection, which declined rapidly over time. Disappearance of hAFP from the serum was complete by 3-4 weeks after administration and was accompanied by robust antibody responses to hAFP and loss of infected cells. After lung delivery, hAFP could be detected in both serum and BAL. This allowed the analysis of the kinetics of gene expression in the lung without sacrificing the animals. In both liver and lung, immunohistochemical analysis correlated well with hAFP levels as detected in serum or BAL, indicating that serum levels were a reliable marker of tissue expression. Preliminary results with a mouse AFP expressed in a helper-dependent adenoviral vector indicate that use of a species-specific version of AFP will eliminate the complication of antibody development. These initial evaluations suggest that AFP is useful as a reporter gene to evaluate gene expression of therapeutic cassettes in multiple tissues, and it should be considered for use in human subjects.

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SYNOPSIS Sixteen patients with migraine were treated prophylactically for 3 months with dazoxiben, a specific thromboxane synthetase inhibitor, in an open study, Frequency of all attacks was reduced by more than 50% in 7 patients, and of severe attacks in 8 of 10 patients who initially suffered severe attacks. Reductions in thromboxane B2 levels measured at intervals during treatment by radioimmunoassay may have reflected standards of compliance with the 6‐hourly treatment regimen. However, a relationship emerged between thromboxane reduction and clinical response, with significantly greater reductions observed in patients who reported good symptomatic relief. This appears to support the hypothesis that platelet activation features in migraine causation.