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FDA Approved Drugs that May Fight HIV

  • Published: 2010-08-21 : Author: University of Minnesota
  • Synopsis: Two drugs that when combined may serve as an effective treatment for HIV.

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Researchers at the University of Minnesota Academic Health Center have identified two drugs that, when combined, may serve as an effective treatment for HIV.

"The findings provide hope that such an approach will someday help the 33 million people worldwide who currently live with HIV," Mansky said.

"HIV's ability to mutate makes it difficult to target and treat," Mansky said. "We wanted to take advantage of this behavior by stimulating HIV's mutation rate, essentially using the virus as a weapon against itself." AHC - Image - Content - Size C - Red pills HIV drugs Full Text

Researchers at the University of Minnesota Academic Health Center have identified two drugs that, when combined, may serve as an effective treatment for HIV.

The two drugs, Decitabine and gemcitabine - both FDA approved and currently used in pre-cancer and cancer therapy - were found to eliminate HIV infection in the mouse model by causing the virus to mutate itself to death - an outcome researchers dubbed "lethal mutagenesis."

This is a landmark finding in HIV research because it is the first time this novel approach has been used to attack the deadly virus without causing toxic side effects. Because Decitabine and gemcitabine are already FDA approved, researchers believe that if their research is effective in large animal models, it will be much easier to expedite the development of the drugs for human use.

The study is a collaboration between molecular virologists Louis Mansky, Ph.D., and Christine Clouser, Ph.D., of the Institute for Molecular Virology and School of Dentistry, as well as medicinal chemist Steven Patterson, Ph.D., from the Center for Drug Design. The findings were recently published online in the Journal of Virology.

"The findings provide hope that such an approach will someday help the 33 million people worldwide who currently live with HIV," Mansky said.

Lethal mutagenesis

HIV mutates and evolves quickly. Rather than inhibiting virus growth and replication like current HIV drugs, this new drug combination forces the virus to do just the opposite - evolve beyond control, to the point of extinction.

"HIV's ability to mutate makes it difficult to target and treat," Mansky said. "We wanted to take advantage of this behavior by stimulating HIV's mutation rate, essentially using the virus as a weapon against itself."

Drug repositioning

One way to decrease cost and expedite the development of novel drugs is by the use of drug repositioning, the process of taking a drug that is used to treat one medical condition, and using it to treat a different illness.

By examining drugs that are already approved by the Food and Drug Administration, the researchers hope to expedite the development of this drug combination because the safety profiles of the two drugs are known.

U of M researchers found that the drug concentrations needed to eliminate HIV infection cause no measurable cell toxicity and were effective against HIV cultures at concentrations well below the current levels used for cancer treatment.

The path ahead

Gemcitabine and decitabine have been administered in pre-clinical trials with mice. Initial findings confirm that the drugs are an effective antiviral therapy for HIV.

The researchers are now in the process of modifying the drugs to forms that can be absorbed by the human body when taken orally.

The study was funded by the Center for Drug Design, Academic Health Center and the National Institutes of Health. About the Academic Health Center - The University of Minnesota Academic Health Center is driven to discover and educate to find new treatments and cures in the areas of diabetes, infectious disease, neurosciences, cancer, and cardiovascular disease. Comprised of the University of Minnesota's six health professional schools and colleges as well as several health-related centers and institutes, the Academic Health Center is a leader in research and training new health professionals. Founded in 1851, the University is one of the oldest and largest land grant institutions in the country.

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