Missouri S&T chemist developing treatment for HIV-related dementia

Posted by
On January 14, 2008

A National Institutes of Health grant is helping fund a Missouri University
of Science and Technology chemist’s research into the treatment of HIV-1
associated dementia.

Dr. Nuran Ercal, professor of chemistry at Missouri S&T and adjunct
associate professor of internal medicine at St. Louis University, was awarded a
$225,750 one-year grant to continue researching the effects of antioxidant
N-acetyl cysteine amide (NACA) as a treatment for HIV-1 associate dementia.

HIV/AIDS is now one of the top-five leading causes of death worldwide, and
36 million people currently are infected with HIV, Ercal says. One-third of
adults with HIV and half of children with HIV develop HIV-1 associated
dementia, which causes behavioral and cognitive dysfunctions.

Ercal and a group of student researchers found that two toxic HIV proteins,
glycoprotein (gp120) and transregulatory protein (Tat), cause the production of
free radicals in the blood brain barrier, which controls the entry of
substances from the blood into the brain.

“When that happens, many other toxins will get into the brain, causing HIV-1
associated dementia,” Ercal says.

Collaborating with Dr. William Banks, professor of geriatric medicine at St.
Louis University, Ercal’s group incubated blood brain barrier cell cultures
with the toxic proteins. When NACA also was used in the cultures, cell
viability increased. NACA is unique because it is able to pass easily through
cell membranes.

HIV-1 associated dementia occurs at a higher rate in HIV patients who also
use drugs like methamphetamine, morphine and alcohol. According to Ercal, the
main propagative force behind the spread of HIV in some parts of the world is
the drug-abusing population. Because of this, Ercal’s group also incubated
blood brain barrier cell cultures with a mix of toxic HIV proteins and

“We chose methamphetamine because it is widely used in Missouri and also
causes free radical formation,” Ercal says.

Cells incubated with both the HIV proteins and methamphetamine showed a
higher rate of free radical formation than cells incubated with the proteins
alone. However, NACA still was able to reduce the oxidative stress on the blood
brain barrier, even when methamphetamine was present.

Ercal and her team now are ready to take their research to the next level
using transgenic mice that have been genetically modified to contain gp120,
allowing researchers to further study the effects of this protein. The study
will be done at Missouri S&T campus using synthetic methamphetamine
obtained from a chemical company.

“We are hoping the free radical formation will be higher in transgenic
animals given methamphetamines, and that NACA will decrease that formation and
perhaps protect the animals,” Ercal says.

It will likely be another five to 10 years before NACA has undergone enough
testing to be commercially available for this purpose. However, if further
research proves the success of the drug at treating HIV-1 associated dementia,
it could improve the quality of life of those infected with HIV.

"People infected with HIV are living longer lives, but they are
suffering from this dementia at a very early age,” Ercal says. “Children are
getting this dementia – nobody expected that.”

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On January 14, 2008. Posted in Research