AEGiS-SC: Key Finding in Fight Against AIDS Dementia; S.F. researchers believe blood test could detect onset

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Key Finding in Fight Against AIDS Dementia; S.F. researchers believe blood test could detect onset

San Francisco Chronicle - The Voice of the West, 901 Mission Street, San Francisco, CA 94119 - Friday, March 14, 1997 - Page A2
David Perlman, Chronicle Science Editor

In a major step toward understanding the dementia that disables the minds of many AIDS patients, San Francisco researchers have found that a class of immune system cells infected by the AIDS virus can cause the disorder by inducing the brain's vital nerve cells to destroy themselves. The new evidence could yield the first blood test to detect the slow onset of AIDS dementia and enable scientists to screen new drugs for treating or even preventing the devastating condition, researchers believe. The discovery that certain blood cells can actually cause neurons in the brain to self-destruct may also apply to other far more common brain disorders unrelated to AIDS. Examples given by the researchers include Alzheimer's disease; Parkinsonism, a nervous disease that resembles Parkinson's disease; or even the effects of stroke on the brain. Headed by Dr. Lynn Pulliam, chief of microbiology at the Veterans Affairs Medical Center in San Francisco, the research team is reporting the results of its latest laboratory experiments in the current issue of the Lancet, a leading British medical journal. Pulliam is also on the faculty of the University of California at San Francisco. Among her colleagues on the team is Dr. Michael McGrath of UCSF, an AIDS laboratory researcher at San Francisco General Hospital. For many years, the team has been studying a variety of neurological diseases by culturing human brain cells in the laboratory. Most recently, they have focused on cells of the immune system called macrophages, which act as a reservoir for HIV, the virus that causes

AIDS.

As the researchers investigated the properties of certain types of unusually dense and granular macrophages that circulate in the human bloodstream, the scientists found a mystery: When they removed all traces of HIV from those macrophages, Pulliam said, the remaining virus-free fluid contained a variety of molecules the researchers have not yet identified. Those mysterious "factors," as Pulliam called them, apparently caused genes within the brain's neurons to begin a process known as apoptosis, or "programmed cell death," that killed off all the brain cells in a kind of mass cell suicide. Because the process of apoptosis is apparently regulated genetically, Pulliam said, she and her colleagues are already seeking a way to forestall the death of the brain cells by disarming the genes that cause the process -- an experimental technique known as gene therapy. If blood tests show that increased numbers of blood-borne macrophages in AIDS patients are a signal that the slow process of brain cell apoptosis is starting, then regular blood tests could be a valuable tool for detecting the earliest stages of dementia long before the disorder's devastating symptoms arise, McGrath believes. And new drugs, he says, could be used to target the HIV-infected macrophages and thus halt the death of brain cells before dementia becomes even moderately severe. The disorder known as AIDS dementia complex affects as many as one-third of adults infected with HIV, and one-half of all children with AIDS. It can cause increasing memory loss, progressive inability to concentrate and, ultimately, major mental disability and paralysis. Although there is no approved treatment for the condition, the new combinations of antiviral AIDS drugs may help slow the development of dementia by lowering the concentration of HIV in the body, specialists say.
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