New therapy for neurons

A U of C researcher has discovered a drug therapy to help AIDS-related dementia.

Dr. Christopher Power, a physician-scientist in the department of clinical neurosciences of the University of Calgary Faculty of Medicine, just published a study, along with scientists at the University of British Columbia, that has not only identified the underlying cause of AIDS-related dementia but has discovered a potential drug therapy.

AIDS-related dementia, seen only in HIV-infected patients, was known to result in neuron damage within the brain. Dr. Power discovered how HIV initiates the destruction.

His study found that an otherwise harmless enzyme, MMP-2, is triggered by HIV to degrade a certain molecule, SDF-1. This degraded SDF-1 is extremely toxic and kills the surrounding brain cells.

"What is unique is the ability of HIV to activate the enzyme MMP-2," specified Dr. Power. "These findings led us to explore whether we could block the toxic effects of MMP-2 using drugs that inhibit the protein."

"An outstanding neuroscience group, both experimentally and clinically… the University of Calgary provides a very unique opportunity for people such as myself [physician-researchers]," said Dr. Power of what brought him to Calgary.

Dr. Power is currently the only neurologist in Canada researching treatments for AIDS-related dementia while also treating patients. He emphasized this "unique" environment, along with the strong support from major funding agencies, enables studies, and therefore discoveries, such as his.

"None of this could be done without it," he said.

Using drugs currently in trial for cancer treatment already known to inhibit various proteins, Dr. Power was able to stop MMP-2 from degrading SDF-1. Without the presence of the degraded SDF-1 molecule, he hoped the progression of neural damage would cease and his hypothesis tested true. By using those drugs as controls in his study he was able to stop AIDS-related dementia, conclusively proving this reaction is its root.

However, in using a drug as a control in the study, Dr. Power had identified not only the mechanism, but also a possible treatment.

"We were thrilled to discover that these drugs are extremely effective in protecting the brain from the devastating attack by the AIDS virus," said Dr. Power. "The team and I are revved up about the new avenues for potential treatment for patients with AIDS-related dementia and perhaps other types of dementia."

These "new avenues" could not have been discovered at a better time, as the incidence of neuro- logical diseases is currently on the rise in HIV-infected people. Neurological impairments are becoming a major determinant in quality of life as highly active antiretroviral therapy lengthens the lifespan of infected people.

Currently, almost 90 per cent of HIV patients experience neurological illnesses. Over 20 per cent are afflicted by AIDS-related dementia alone. Patients initially experience losses in memory, concentration, motor-skills and balance, but effects become much more severe further down the road.

"Neurons aren’t firing properly," explained Dr. Power, "Patients can become vegetative with time."

Despite this growing need for new treatments, there is much to be learned about diseases like AIDS-related dementia before drug treatments such as the one discovered by Dr. Power will help patients.

"We are chiefly concerned with the underlying mechanism. I regard drug development as important but the drug was not the focus of the study," stressed Dr. Power. "We need to be sure of the underlying mechanism in the first place."

Dr. Power said he would next like to do a clinical trial and look deeper into what exactly makes HIV activate normal brain constituents in such a toxic way.

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