- Steve Addazio's inaugural press conference as Boston College head football coach (pg. 9)
- Wake Forest University president Nathan Hatch's keynote address at the Sesquicentennial symposium "Religion and the Liberal Aims of Higher Education" (pg. 34)
- David B. Couturier, OFM Cap., on "New Evangelization for Today's Parish" (pg. 42)
- Guerilla Orchestra: the Callithumpian Consort and student musicians rehearse John Zorn's Cobra (pg. 10)
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How does AIDS enter the brain?
While death rates from AIDS have been falling worldwide, there has been no comparable decline in the prevalence of AIDS-related dementia. Such cases continue to pile up, mainly because, with the advent of antiretroviral drugs, AIDS sufferers are living longer.
Between 30 and 40 percent of AIDS patients have brain-related illnesses linked to their disease, according to figures cited by associate biology professor Kenneth Williams, who came to Boston College in 2007 (after a decade of research at Harvard Medical School) to conduct basic research into the cellular science of AIDS. For some time, Williams says, researchers have suspected that the AIDS virus doesn’t cause neurological and cognitive damage on its own, that it works through other means. He and his 12-member team in Higgins Hall have gained recognition for identifying the agent—a particular kind of white blood cell that, like a Trojan horse, traffics HIV into the brain.
The cells are called monocytes, which, in a healthy body, help to get rid of foreign material such as bacteria and viruses. They start off in the bone marrow and circulate in the bloodstream before finding a home in various bodily tissues—the liver, for instance, or the lungs. There, they develop into a potent, devouring form called a macrophage, which has been branded the “main scavenger” cell of the body’s immune system. If HIV-bearing monocytes find a home in the brain, says Williams, they become what he likes to call macrophage “bad-guys,” infecting the organ and releasing chemicals that damage neurons.
“Potentially, you could stop or reverse brain disease and AIDS dementia” by depleting immune systems of these cells, says Williams, who has done just that, in experiments involving monkeys with SIV/AIDS, the simian version of the disease. In those experiments, conducted at Massachusetts General Hospital, brain disease either slowed significantly or reversed altogether.
Working with collaborators from several institutions, Williams has fleshed out these findings in a recent flurry of papers published in leading scientific journals.
In the May 2009 edition of the American Journal of Pathology, for example, he and five coauthors reported on a study (of infected primates) in which the researchers genetically modified stem cells, decreasing a receptor for HIV so that the cells could not be infected with the virus. The stem cells were used in the marrow to cultivate monocytes, and the monocytes that reached the brain remained virus-free. Indeed, HIV-free monocytes/macrophages continued to be found in the brain tissue for more than four years, leading the researchers to conclude that stem cells resistant to HIV could restore a healthy population of macrophages to the damaged brains of AIDS sufferers.
In a study published April 28, 2009, in Neurology, Williams and another set of collaborators, using brain imaging and other techniques, found that neurological injuries in humans with AIDS usually take place within two to three weeks of a person’s initial exposure to the virus. This is sooner than many experts had believed, and highlights the need for early treatment, says Williams.
A paper prepared for publication in PLoS Pathogens correlates high quantities of monocytes leaving the bone marrow of AIDS-infected laboratory animals with development of rapid AIDS and the severe AIDS-related encephalitis, an inflammation of the brain. The coauthors of that paper include five members of Williams’s team in the biology department: research professor Tricia Burdo, who took the lead in the effort; undergraduate students Jessica Button ’10 and Krystyna Orzechowski ’10; post-doctoral associates Anitha Krishnan and Caroline Soulas; and Williams.
With a $10 million grant from the National Institutes of Health, Williams is now overseeing clinical trials of a drug that might halt the invasion of infected monocytes into the brain. The project involves researchers at the University of California, San Francisco, and the University of Hawaii, as well as an industrial partner, California-based drug maker Pathologica.
Many researchers were initially skeptical of Williams’s theory of the emergence of specific populations of bone marrow–derived cells that go on to damage the central nervous system, notes Howard E. Gendelman, who chairs the department of pharmacology and experimental neuroscience at the University of Nebraska Medical Center and is considered a founder of the field of monocyte-macrophage research. Gendleman says he counted himself among the skeptics, but adds, “Ken has simply revolutionized the field” by demonstrating his case.