An antibiotic commonly used to treat a variety of serious infections may also help prevent dementia in HIV patients, according to a test-tube study of human brain cells by Johns Hopkins University School of Medicine neurologist Jeffrey Rumbaugh, M.D., Ph.D.
Results of the lab study with ceftriaxone are expected to be presented at the American Academy of Neurology's 58th annual meeting on April 5 in San Diego, Calif.
Rumbaugh added that, although ceftriaxone is FDA approved and could be used at any time by patients suffering from HIV dementia, there is not yet enough data to support doing so.
The study looked at two proteins, called Tat and gp120, that are part of the virus that causes HIV infection and that are implicated in the development of HIV dementia, according to Dr. Rumbaugh, the study's lead author. HIV is the only virus that makes Tat and gp120, which are produced during its normal life cycle, though other viruses make similar proteins. Dementia is a common side effect of long-term HIV infection, but there are no known specific treatments for this complication. According to Rumbaugh, Tat and gp120 are believed to cause dementia by reducing the expression of a brain chemical called EAAT-2 (excitatory amino acid transporter-2). EAAT-2 absorbs the neurotransmitter glutamate from the space between neurons (the synapse), thereby preventing excess neuronal excitation, which in turn can cause cell death and brain damage.
Ceftriaxone, used to treat pneumonias, sexually transmitted diseases, bacterial meningitis and other infections, is a known stimulator of EAAT-2 expression and protects against neuronal injury in mice with nervous system disorders. To test ceftriaxone's potential in HIV, Rumbaugh and colleagues grew human neuronal cell cultures in a lab from existing human neuron cell lines, treated them with a range of doses of ceftriaxone, and exposed them to Tat or gp120. They found that the antibiotic protected the neurons against both HIV proteins. The dose of ceftriaxone needed for protection was well within the range currently used for treatment of bacterial infections.
"These results indicated that this class of drugs may prove effective in treating HIV patients with dementia," Rumbaugh says.
About 500,000 people in the United States alone have HIV dementia. And although new cases of HIV dementia have declined over the last 10 years (due to the increased availability of effective HIV treatments), the prevalence of HIV dementia is on the rise since people are living longer with HIV.
"We hope this research might help many patients with other forms of dementia, such as Alzheimer's, and infections of the brain, like herpes encephalitis and West Nile encephalitis," says Rumbaugh. "However, it will require a lot more development before drugs like these can be used even to treat patients with HIV dementia, let alone to treat patients with other neurological diseases."
Other researchers in this study include Jeffrey Rothstein, M.D., Ph.D., and Avindra Nath, M.D., both professors in the Department of Neurology at the Johns Hopkins University School of Medicine.
This study was supported by grants from the National Institutes of Health.
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