Antioxidants could reduce HIV-related dementia

A new treatment in development at Missouri S&T could improve the quality of life for more than 36 million people currently infected with HIV. One-third of adults with HIV and half of children with HIV develop HIV-1 associated dementia, which causes behavioral and cognitive dysfunctions.

“People infected with HIV are living longer lives, but they are suffering from this dementia at a very early age,” says Nuran Ercal, professor of chemistry at Missouri S&T and an adjunct professor of internal medicine at St. Louis University. “Children are getting this dementia – nobody expected that.”

A $225,750 National Institutes of Health grant is helping fund research by Ercal to continue researching the effects of antioxidant N-acetyl cysteine amide (NACA) as a treatment for HIV-1 associated dementia.

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 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.

HIV-1 associated dementia occurs at a higher rate in HIV patients who also use drugs like methamphetamine, morphine and alcohol. Because of this, Ercal’s group also incubated blood brain barrier cell cultures with a mix of toxic HIV proteins and methamphetamines.

“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 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 on the Missouri S&T campus using synthetic methamphetamine obtained from a chemical company.

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.

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