Beauty and the Beast

A new study has revealed that morphine, a derivative of the opium poppy that is similar to heroin, protects rat neurons against HIV toxicity -- a finding that researchers say could help in the design of new therapies for patients who are infected with the virus.

The discovery, presented at the annual meeting of the Society of NeuroImmune Pharmacology, also helps explain why a subset of people who are heroin abusers and become infected with HIV through needle sharing don't develop HIV-related brain dementia. This brain disorder includes cognitive and motor abnormalities, anxiety, and depression.

"We believe that morphine may be neuro!protective in a subset of people infected with HIV," says the study's lead investigator, Italo Mocchetti, Ph.D., a professor of neuroscience at Georgetown University Medical Center. "That is not to say that people should use heroin to protect themselves -- that makes no medical sense at all -- but our findings give us ideas about designing drugs that could be of benefit."

The researchers initiated the study because they knew that a number of HIV-positive people are also heroin abusers, and because of that, these people are at high risk of developing neurological complications from the infection. Others, however, never develop these cognitive problems, Mocchetti says. "Needless to say," he adds, "we were very surprised at the findings. We started with the opposite hypothesis -- that heroin was going to destroy neurons in the brain and lead to [HIV-related] dementia."

Because little is known about the molecular mechanisms linking opiates and neurotoxicity caused by HIV in humans, Mocchetti and his team conducted experiments in rats. They found that in the brain, morphine inhibited the toxic property of the HIV protein gp120, which mediates the infection of immune cells. With further investigation, they concluded that morphine induces production of the protein CCL5, which they discovered is released by brain cells. CCL5 is known to activate factors that suppress HIV infection of human immune cells. "[We knew this protein is] important in blood, but we didn't know it is secreted in the brain," Mocchetti says. "Our hypothesis is that it is in the brain to prevent neurons from dying."

Mocchetti and his team members say morphine blocked HIV from binding to CCR5 receptors on CD4 cells -- a method it typically uses to enter and infect these immune-system protectors. The researchers believe CCL5 itself attached to those receptors, preventing the virus from using it. In this way it prevented HIV-associated dementia. This effect, however, worked only in the M-trophic strain of HIV, the strain that most people are first infected with. It did not work with the second, T-trophic strain that often infects patients later.

"Ideally," Mocchetti says, "we can use this information to develop a morphine-like compound that does not have the typical dependency and tolerance issues that morphine has.