Scientists from the University of Calgary in Alberta and the University of British Columbia in Vancouver have found that HIV triggers an enzyme in white blood cells that kills nerve cells in the brain. The enzyme, known as Metalloproteinase-2 or MMP2, changes a molecule required for normal brain growth and function. The altered molecule becomes highly toxic and destroys brain nerve cells, giving rise to symptoms of dementia.
It is the first study to unravel the mechanics of how dementia and memory loss is caused in HIV patients. In addition, the researchers also found they could block the toxic effects of MMP2 by using drugs already in clinical trials for cancer treatment.
"We now understand how this enzyme becomes a killing machine," says Christopher Overall, Canada Research Chair in Metalloproteinase Biology at UBC. "This is exciting news for patients because we think dementia can be slowed or stopped by adding another protease blocker to the drug cocktails now used to treat HIV."
More than 20 per cent of people with AIDS experience dementia during the course of their illness. A rapidly progressive condition, HIV dementia is characterized by impaired concentration and problem solving, forgetfulness, as well as motor abnormalities such as slurred speech and difficulties with movement.
The findings of the two-year study, completed with principal co-investigator Christopher Power of the University of Calgary, were reported recently in Nature Neuroscience. Members of Overall's lab at the UBC Faculty of Dentistry completed biochemical assays and identified the toxic protein that allowed Power, a neurologist who treats people with HIV dementia, to test MMP2 on HIV-infected cells.
"The team and I are revved up about the new avenues of potential treatment for people with HIV and perhaps for other types of dementia, such as Alzheimer's disease," says Power, physician-scientist in the Dept. of Clinical Neurosciences at the University of Calgary Faculty of Medicine.
Overall has been in discussions with pharmaceutical companies interested in testing the effectiveness of cancer drugs like Prinomastat to block the killer enzyme. The scientists estimate it may be five to 10 years before the drug is available to patients. According to UNAIDS, more than 800,000 people have AIDS in the U.S. Some 42 million people worldwide are infected with HIV or have AIDS, including an estimated 12 million youth.