AIDS Dementia Patients May Benefit from Anti-Inflammatories

      There''s a marker found in the blood of patients with both Alzheimer''s disease and AIDS dementia, and recent research shows it''s an inflammatory marker.

      This raises the question of whether anti-inflammatory drugs may be beneficial to patients with dementia, according to Lynn Pulliam, PhD, a researcher in the field of neurovirology.

      Pulliam is a professor at the University of California, San Francisco, and chief of Microbiology at the Veterans Affairs Medical Center in San Francisco. She spoke on her research in the field of dementia, as well as the latest advances in neurovirology at the American Medical Association''s 19th Annual Science Reporters Conference held in Atlanta, Georgia, October 1-2, 2000.

      Ultimately, researchers want to discover if anti-inflammatories would be useful in treating dementia or in even preventing it in people who appear genetically predisposed to dementia. Pulliam has submitted for publication laboratory results using a compound with anti-inflammatory properties that reverses neurotoxins associated with AIDS dementia. "If it bears out that anti-inflammatories are useful, it''s potentially a relatively simple approach to therapy," says Pulliam.

      Following along the theme of genetic markers for dementia, Pulliam reported on research she has been conducting on AIDS patients with dementia. While AIDS patients are living much longer with the drugs currently available, she discovered that those with dementia face the threat of the dementia becoming chronic. Prior to the new drug therapies for AIDS, the dementia was acute and lethal. Now, while patients appear to be feeling better, the markers for dementia remain despite the drug therapies these patients undergo. They are found at lower levels, but they remain in the system.

      Pulliam was chair of an International Symposium on neurovirology two weeks prior to the AMA conference and presented the latest findings. "A very hot topic right now is the use of altered viruses to treat brain tumors. There are a couple of viruses that go straight to the brain. They are the herpesvirus, which is typically latent in the brain, and polio. These viruses are being altered so they are not neurovirulent, rendering them safe. These viruses are administered and serve as carriers of genes or cytokines that go to the brain and turn off a tumor''s ability to replicate.

      "Research using this approach is in very early phases, and obviously, there is much to learn. But the concept is such that this system could be used following brain surgery to go after those one or two cells that couldn''t be removed. Or, it could be used for tumors that are inoperable," she explains.

      There were new data linking the human virus, JCV, which causes the fatal demyelinating (destruction of sheath around certain nerve fibers) disease called PML (progressive multifocal leukoencephalopathy) with tumors. It now appears that when the JCV regulatory protein, T antigen, is expressed in mice, the mice develop tumors resembling human medulloblastomas, a common malignant brain tumor in children. When the researchers looked at human medulloblastomas, they found a high frequency of JCV DNA sequences and detected the JCV T antigen. This suggests that JCV may play a role in human medulloblastomas.

      A new encephalitis screening program underway in California was described that will eventually help physicians diagnose the viral causes of brain inflammation.

      "The first thing a doctor thinks of when a patient presents with encephalitis is that it is herpes, because herpes is the most common cause of encephalitis. But when herpes is ruled out, it becomes more difficult to decipher. And because encephalitis progresses so rapidly, you may be relying upon family and friends to provide a history of the patient. Perhaps the patient traveled to some place with mosquitoes, or was exposed to animals on a farm, or recently cleaned out an attic. Worse yet, you may be relying on an autopsy because encephalitis progresses so rapidly.

      "The screening program in California is one where all information from encephalitis patients in the state are entered into a database - lab results, spinal fluid results, history. And physicians can use the database to try and draw conclusions about the viral cause of a particular case of encephalitis," she explains.

      Pulliam says there are several emerging viruses that can impact the brain, and that gathering information on these is particularly important.

      "There''s the West Nile Virus, which has had quite a bit of press and most people are familiar with. But there''s also the Nipah Virus in Malaysia, which caused 105 fatalities from September 1998 to May 1999. Epidemiology studies showed that the virus is spread to humans by close contact with sick pigs. Some of the pigs appeared to have a respiratory virus but some did not appear ill. It is speculated that the fruit bat is a reservoir and it''s unknown how the virus is transmitted from bats to pigs."

      She says one of the biggest challenges in treating viruses is the limitation in the number of antivirals available. "We really only have acyclovir and ribavirin. That''s just about it and it certainly is not enough. Anything else is still in clinical trials. Needless to say, doctors hold out a lot of hope for therapies that are yet to come."

      This article was prepared by AIDS Weekly editors from staff and other reports.

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