Taking a Tryp with its Twists and Turns Across the Blood-Brain Barrier

Date/Time: 11 July 2012, 10:15 AM - 11:15 AM
Speaker: Dennis Grab, Ph.D.
Speaker Affiliation: Associate Professor, Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins University School of Medicine Baltimore, Maryland
Venue: John A. Burns School of Medicine, Kaka’ako, MEB Auditorium (Room 315)

For more info: Cori Watanabe (808) 692-1654
Description: Human African trypanosomiasis (HAT), commonly called sleeping sickness, has been claimed to be more deadly than other vector-borne diseases, such as malaria, because death is inevitable if a patient is untreated. The terminal stages of human sleeping sickness are characterized by neurologic signs, progressive coma, seizures and a marked increase in night-time insomnia and daytime drowsiness (from which the disease gets its name). Sleeping sickness is caused by two subspecies of African trypanosomes (Trypanosoma brucei rhodesiense and T. b. gambiense, causing East African and West African sleeping sickness, respectively). In classical late-stage human sleeping sickness the parasites invade the central nervous system (CNS) and infected individuals suffer from progressive neurologic involvement with concomitant psychiatric disorders and, if untreated, death. Once inside the brain, the parasites are shielded from many of the most effective trypanocidal drugs. Indeed, the brain is probably the source for many relapse infections.

When this work was started in 2002, there was a general appreciation that in late-stage HAT, a major factor in pathogenesis was the ability of the trypanosome to cross the blood-brain barrier (BBB) and enter the CNS. At that time, very little was known about how trypanosomes achieved passage across the functional unit of the BBB comprised of human brain. In this talk, our progress to delineate the mechanism of African trypanosome traversal across the human BBB at the molecular and cellular levels will be reviewed, with the hope that this research will lead to more effective therapies against this deadly parasite.