Patent ID: 7767880

Claim:
A method of screening an agent in vivo for an activity in the brain or central nervous system (CNS) and an ability to transit the blood brain barrier, the method comprising: (a) administering the agent, without regard to whether the agent penetrates the blood brain barrier, to a zebrafish embryo, wherein the zebrafish embryo is an embryo of at least the late stage of gastrulation but having not yet developed a blood brain barrier comprising tight junctions when initially contacted with the agent, whereby when cultured at a standard temperature of about 28° C. the zebrafish embryo is aged at least about nine hours post fertilization but less than three days post fertilization when initially contacted with the agent; (b) detecting a response in the brain or CNS of the agent-treated zebrafish of step (a) in vivo; (c) comparing the response in the brain or CNS of the agent-treated zebrafish of step (a) with a response in the brain or CNS of an untreated or control zebrafish, wherein a difference in the response in the brain or CNS of the agent-treated zebrafish of step (a) compared to the response in the brain or CNS of the untreated or control zebrafish is indicative of the agent having activity in the brain or CNS; (d) if the agent is determined by step (c) to have activity in the brain or CNS, administering the agent to a zebrafish having a blood brain barrier comprising tight junctions when initially contacted with the agent, whereby when cultured at a standard temperature of about 28° C. the zebrafish is aged at least three days post fertilization when initially contacted with the agent; (e) detecting a response, if any, in the brain or CNS of the agent-treated zebrafish of step (d); and (f) comparing the response in the brain or CNS of the agent-treated zebrafish of step (d) with a response in the brain or CNS of an untreated or control zebrafish, wherein a difference in the response in the brain or CNS of the agent-treated zebrafish of step (d) compared to the response in the brain or CNS of the untreated or control zebrafish is indicative of the agent having an ability to transit the blood brain barrier.