United Press International - Friday, 11 May 2001

Dr. Avindra Nath, a neurologist with the University of Kentucky in Lexington, said Friday he has not only discovered the specific cellular activity that leads to dementia in patients with HIV, but has developed a way to prevent the activity in the laboratory using antioxidants.

He presented his preliminary findings at American Academy of Neurology's 53rd Annual Meeting in Philadelphia.

"By examining the cerebrospinal fluid of HIV patients we found that the virus affects the mitochondria in their cells," he told United Press International. Mitochondria are small, threadlike particles in the cytoplasm, the fluid inside the cell walls. Mitochondria are responsible for cellular energy and cell breathing, literally controlling cell life.

After developing a test to measure mitochondrial activity, Nath and colleagues then compared spinal fluid of 30 patients with HIV dementia --16 patients lacking symptoms and another 20 patients with other neurological problems, including multiple sclerosis and chronic headaches.

They found that in HIV patients, mitochondrial activity was incrementally depressed as HIV levels increased in the CSF of patients and dementia progressed.

"CSF from patients with HIV infection causes mitochondrial dysfunction with increasing severity of dementia," Nath said. "Next we tested several antioxidant preparations known to protect the mitochondria in the cell cultures to see what effect if any they might have.

"We found six out of seven of these antioxidants reduced the toxicity level of the CSF and protected the mitochondria in these cell cultures. We were quite surprised."

According to the researcher, if the agents have the same protective effect if given to HIV patients, it might help prevent or at least delay the progressive dementia of the virus once it crosses the blood-brain barrier.

One the drugs, L-deprenyl, will be soon be tested in a clinical trial. Three of the compounds (didox, trimidox and imidate) are analogs of hydroxyurea with known antiretroviral activity., making them especially attractive for clinical trials with HIV patients.

"This research is still very preliminary," Nath said. "But if we can duplicate these findings in a clinical setting using one of these compounds we could perhaps stop the virus from replicating while protecting the mitochondria at the same time."

Antioxidants are natural enzymes that inactivate so-called oxygen free radicals -- very reactive particles that can trigger chain reactions capable of causing damage to different biological targets such as cells, proteins, lipids and DNA. Recently free-radical mechanisms have been implicated in the pathology of many human diseases including cancer, stroke, malaria, arthritis, neurodegenerative diseases as well as in aging and HIV infections.

Dr. Alex Sinclair, a neurologist with the University of California, Los Angeles, told UPI that such findings underscore the necessity of continuing to pursue additional treatments for individual HIV-related conditions despite the availability of effective antiretroviral drugs that can significantly reduce the prognosis of the disease.

"It's an exciting finding because these hydroxyurea compounds are readily available and fairly inexpensive," he said. "If clinical trials go well, they could play a valuable role in treatment of patents with HIV and, possibly, with other neurodegenerative diseases."

It is currently estimated that 8 to 16 percent of people with AIDS develop dementia, usually in later stages of the disease.

(Reported by UPI Medical Writer Kurt Samson in Washington.)

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