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
Johns Hopkins University School of Medicine neurologist
Results of the lab study with ceftriaxone were
presented recently at the American Academy of Neurology's
58th annual meeting, held in San Diego, Calif.
Rumbaugh said 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,
said 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,"
About 500,000 people in the United States alone have
HIV dementia. And although new cases 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," Rumbaugh said. "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, which was supported
by grants from the National Institutes of Health, are
Jeffrey Rothstein and Avindra Nath, both professors in the
Neurology at the School of Medicine.