{"id":47345,"date":"2000-01-24T00:00:00","date_gmt":"2000-01-24T06:00:00","guid":{"rendered":"https:\/\/www.unmc.edu\/newsroom\/2000\/01\/24\/results-published-in-january-issue-of-neurology\/"},"modified":"2022-08-29T10:56:13","modified_gmt":"2022-08-29T15:56:13","slug":"results-published-in-january-issue-of-neurology","status":"publish","type":"post","link":"https:\/\/www.unmc.edu\/newsroom\/2000\/01\/24\/results-published-in-january-issue-of-neurology\/","title":{"rendered":"Results Published in January Issue of Neurology"},"content":{"rendered":"

<\/FONT><\/I><\/B><\/p>\n


Unique Mouse Model Allows UNMC Researchers to Determine<\/p>\n

Most Effective Drugs in Treating HIV-dementia<\/FONT><\/B><\/p>\n

Two of five commonly used drugs to fight HIV have been shown by University<\/p>\n

of Nebraska Medical Center researchers to be effective against hard-to-treat<\/p>\n

HIV virus hiding in the brain.<\/p>\n

The effectiveness of drugs in the central nervous system was demonstrated<\/p>\n

for the first time in a unique mouse model that was developed at UNMCs<\/p>\n

Center for Neurovirology and Neurodegenerative Disorders (CNND).<\/p>\n

The severe combined immunodeficiency (SCID) mouse model for HIV-associated<\/p>\n

dementia is unique in that it allows researchers to test which drugs are<\/p>\n

most effective in crossing the blood-brain barrier, the brains natural<\/p>\n

defense mechanism, and destroying hidden reservoirs of HIV.<\/p>\n

Two drugs found most effective were abacavir, known as Ziagen, and lamivudine,<\/p>\n

also known as Epivir or 3TC. They reduced viral levels in the brain by<\/p>\n

80 to 95 percent. Also tested were zidovudine (AZT), didanosine (ddI) and<\/p>\n

stavudine (d4T), which also crossed the blood-brain barrier but were not<\/p>\n

as effective.<\/p>\n

All five drugs tested come from a class of drugs known as nucleoside<\/p>\n

reverse transcriptase inhibitors (NRTI), which work by preventing the virus<\/p>\n

from reproducing. The drugs are commonly used in different combinations,<\/p>\n

or drug cocktails, but UNMCs researchers tested the drugs one at a time.<\/p>\n

Drug cocktails frequently contain a protease inhibitor combined with AZT<\/p>\n

or d4T and 3TC.<\/p>\n

Results of the two-year drug study appear in a lead article in the January<\/p>\n

issue of Neurology, a leading journal of clinical research of neurodegenerative<\/p>\n

disorders. The article is accompanied by an editorial written by Drs. Justin<\/p>\n

McArthur and Karl Kieburtz, senior neurologists at the Johns Hopkins Medical<\/p>\n

Center and Strong Memorial Hospital.<\/p>\n

The $175,000 study was funded by grants from the National Institutes<\/p>\n

of Health and Glaxo Wellcome, Inc., a pharmaceutical company based in Research<\/p>\n

Park Triangle, N.C. Results of a study of drug combinations is now being<\/p>\n

prepared by UNMC scientists.<\/p>\n

Researchers know that HIV penetrates the central nervous system soon<\/p>\n

after infection and sets up residency in the microglia, the brains immune<\/p>\n

system cells. Often, the virus stays dormant in the brain. However, 20<\/p>\n

percent of adults and 50 percent of children with AIDS develop HIV-dementia,<\/p>\n

a devastating complication that causes serious mental and motor deficits.<\/p>\n

In addition to being difficult to destroy, the HIV virus hides in the<\/p>\n

brain ready to re-infect a person with the virus once drug therapy is stopped.<\/p>\n

A greater danger is that it may mutate into a strain resistant to available<\/p>\n

therapies.<\/p>\n

The relationship between the amount of virus in the brain and the onset<\/p>\n

of HIV-associated dementia is poorly understood, said Howard Gendelman,<\/p>\n

M.D., Purtilo professor of pathology and microbiology at UNMC and director<\/p>\n

of the CNND.<\/p>\n

As we get further along with new treatments and modalities, we understand<\/p>\n

that the virus can never be eradicated unless we target the brain, he<\/p>\n

said. For many years, scientists have left it alone. They didnt know<\/p>\n

how to attack the virus in the brain. They didnt understand how to deliver<\/p>\n

drugs that could get into the brain and how to eradicate the virus that<\/p>\n

was protected by a perceived impenetrable barrier. There were no laboratory<\/p>\n

or animal models that were available to allow testing, said Dr. Gendelman,<\/p>\n

senior investigator for the study.<\/p>\n

Principal investigator of the study was Jenae Limoges, M.D., assistant<\/p>\n

professor, Department of Internal Medicine-Infectious Diseases. She said<\/p>\n

that autopsies of the brain provide the only definitive information about<\/p>\n

how the virus affected the brain. The only other animal model that exists<\/p>\n

for testing HIV drugs is the monkey, which is cumbersome, expensive and<\/p>\n

not always reproducible.<\/p>\n

Clinically, we can tell if a patient with dementia is getting better<\/p>\n

while being treated with these drugs. We can use that to presume that the<\/p>\n

infection in the brain is going down, but we dont know for sure, she<\/p>\n

said. The SCID mouse model can quickly and easily show us exactly what<\/p>\n

these drugs are doing in the brain tissue, because we can directly measure<\/p>\n

the number of infected cells.<\/p>\n

For the study, human cells infected with HIV were injected into the<\/p>\n

brains of SCID mice. Because the mice have no immune system, the human<\/p>\n

cells are not rejected. An NRTI drug was then injected into the mouse body.<\/p>\n

After a limited amount of time, the brain tissues were examined for infected<\/p>\n

cells.<\/p>\n

One of the surprising results of the study was that AZT did not perform<\/p>\n

as well as expected. Physicians have noted that patients with HIV-dementia<\/p>\n

improved while on drug therapies that include AZT. Dr. Limoges believes<\/p>\n

this result may be related to the dosage level or differences in metabolism<\/p>\n

of the drug in mice.<\/p>\n

Another result was that new knowledge about the development of HIV-dementia<\/p>\n

was gained through this study. Mice resemble human disease in pathology,<\/p>\n

in mechanisms of brain damage and by limited behavioral testing. This suggests<\/p>\n

that the HIV infected human cells are secreting toxins and causing damage<\/p>\n

to these mouse cells, Dr. Limoges said.<\/p>\n

UNMC is the only public academic health science center in the state.<\/p>\n

Through its commitment to research, education, outreach and patient care,<\/p>\n

UNMC has established itself as one of the countrys leading centers for<\/p>\n

cancer research and treatment, solid organ transplantation and arthritis.<\/p>\n

Nearly $32 million in research grants and contracts were awarded to UNMC<\/p>\n

scientists during the past fiscal year. In addition, UNMCs educational<\/p>\n

programs are responsible for training more health professionals practicing<\/p>\n

in Nebraska than any other institution.<\/p>\n


 <\/p>\n<\/div><\/div>","protected":false},"excerpt":{"rendered":"

Unique Mouse Model Allows UNMC Researchers to Determine Most Effective Drugs in Treating HIV-dementia Two of five commonly used drugs to fight HIV have been shown by University of Nebraska Medical Center researchers to be effective against hard-to-treat HIV virus hiding in the brain. The effectiveness of drugs in the central nervous system was demonstrated […]<\/p>\n","protected":false},"author":79,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-47345","post","type-post","status-publish","format-standard","hentry","category-uncategorized","department-press-release"],"yoast_head":"\nResults Published in January Issue of Neurology<\/title>\n<meta name=\"description\" content=\"Unique Mouse Model Allows UNMC Researchers to Determine Most Effective 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