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HIV Microbicide Passes First Test

A vaginal gel that may potentially be used to prevent transmission of HIV infection appears to be safe and acceptable when used by both HIV-infected and uninfected women, according to results of a Phase I clinical trial conducted by Wafaa El-Sadr, M.D., MPH, professor of clinical medicine at P&S and epidemiology at the Mailman School of Public Health and chief of the Division of Infectious Diseases at Harlem Hospital Center, and other members of the HIV Prevention Trials Network. The study was conducted at Harlem Hospital Center and Bronx Lebanon Hospital Center.

“Globally, women are more severely affected by the HIV epidemic and are in dire need of a method they can use to protect themselves that doesn’t require negotiations with their partners,” Dr. El-Sadr says. “This study is a small but important step toward achieving that goal.”

The trial is the first to test a microbicide that specifically attacks HIV. The active ingredient in the vaginal gel, tenofovir, is an antiretroviral drug widely available in pill form for treatment of HIV-infected individuals. As a vaginal gel, tenofovir has also shown promise in preventing SIV (simian immunodeficiency virus) infection in monkeys.

In this 14-day trial, none of the women experienced life-threatening side effects and only one developed a side effect judged to be severe that was possibly related to gel use. The majority of the side effects experienced by the women were mild to moderate in nature and only one necessitated discontinuation of gel use. The majority of the women and their male partners found the gel highly acceptable. The results were published in the Feb. 28, 2006, issue of the journal AIDS.

A Phase II randomized placebo-controlled trial of tenofovir vaginal gel involving 200 women will shortly be initiated at three sites – in New York City, Alabama, and India. Jessica Justman, M.D., associate director of the Center for Infectious Diseases Epidemiologic Research at Mailman School of Public Health, will lead this effort in collaboration with Dr. El-Sadr. The study will be conducted at the Microbicide Research Site at Bronx Lebanon Hospital Center.

The research was supported by the NIH and gel provided by Gilead Sciences, Inc.

Researchers Find Dementia Common In ALS Patients

Almost 25 percent of patients with amyo-trophic lateral sclerosis (ALS) also show signs of frontal lobe dementia, according to a new study published in the March 2006 issue of the Archives of Neurology.

The surprisingly high percentage suggests that ALS is not just a disease of the motor neurons, says senior author Yaakov Stern, Ph.D., professor of clinical neurology and leader of the Cognitive Neuroscience Division of the Sergievsky Center. Frontal lobe dementia often occurs in ALS patients with a rare inherited form of the disease, but it had been considered rare in patients with the more common, sporadic form of ALS.

The new study is one of the largest to date to examine dementia in ALS. Among 40 patients recruited into the study, 12 (30 percent) showed signs of cognitive impairment, including 9 (23 percent) who met the criteria for dementia. In previous studies, percentages ranged from 2 percent to 50 percent.

Frontal lobe dementia is more subtle than dementia in Alzheimer’s disease. Patients with frontal lobe dementia retain memories but can be impulsive, emotional, and have trouble making decisions. A few studies have suggested that ALS patients with dementia do not survive as long as other patients, possibly because they refuse invasive therapies, but this study found no difference in survival.

The research was supported by the NIH.

Hepatitis C Research Gets Needed Boost

The hepatitis C virus, (HCV), was discovered in 1989 after researchers spent decades looking for a “non-A, non-B” virus that causes chronic liver disease. Despite that breakthrough, HCV continues to frustrate scientists, who until a few months ago hadn’t been able to culture the virus in the lab.

Cells expressing HCV surface proteins E1 and E2 are mixed with receptor-containing liver cells.
Cells expressing HCV surface proteins E1 and E2 are mixed with receptor-containing liver cells. The mixture of cells is transiently exposed to acidic pH to mimic the endosomal environment encountered by the virus upon entry into cells. This results in fusion of the two cell-types and allows for expression of green fluorescent protein. The use of a fluorescent reporter provides a convenient method to understand the mechanism of fusion, to look for the HCV receptors and to screen for anti-viral drugs.
A new assay developed by Ila Singh, M.D., Ph.D., assistant professor of pathology, should help reinvigorate HCV research. The assay gives scientists a way to understand how HCV enters human liver cells and how this can be prevented.

To gain entry, the membrane of the virus must fuse with the cell’s membrane, but many details about HCV fusion, including the receptor it uses to gain entry, are completely unknown.

Dr. Singh’s assay consists of two types of cells: human liver cells that express potential receptors and other cells that express HCV surface proteins needed for fusion. Both cells are engineered in such a way that when the two types successfully fuse, green fluorescence protein is produced and the fused cells glow green. Fusion can be inhibited by specific antibodies and peptides.

Scientists can now easily manipulate the HCV surface proteins to determine how HCV fusion occurs. Potential drugs that inhibit fusion can be quickly screened with the assay.

Dr. Singh hopes the assay becomes as successful as a similar HIV fusion assay, which led to the development of the world’s first anti-fusion drug, Fuzeon, in 2003.

The research was supported by an Irma T. Hirschl Trust Career Scientist Award and the National Institute of Diabetes and Digestive and Kidney Diseases.

Children Benefit When Mother’s Depression Eases

At a time when many questions about the safety of treatments for children with depression remain, alleviating depression in a child’s mother has been found to be an effective way to improve the mental health of her children, according to a new research study led by Myrna Weissman, Ph.D., professor of psychiatry and chief of clinical-genetic epidemiology at the New York State Psychiatric Institute.

Children of depressed parents are two to three times more likely than other children to suffer from depression, anxiety and disruptive disorders, which often begin before adolescence.

The new study of 151 depressed mothers and their children found that overall the number of psychiatric diagnoses in children dropped 11 percent if their mothers recovered from depression after three months of antidepressant treatment. The number of diagnoses in children increased 8 percent when mothers did not respond to treatment. The findings were published in the March 22/29, 2006, issue of JAMA.

The research was supported by the National Institute of Mental Health.

Better Treatment for Clogged Stents

When a bare metal stent implanted in a coronary artery becomes clogged, the best way to unclog it is with a second drug-eluting stent, according to a new study published in the March 15, 2006, issue of JAMA by Columbia interventional cardiologists.

The study compared paclitaxel-eluting stents with a radiation therapy that is the only FDA-approved treatment for clogged bare metal stents, also known as restenosis. This condition occurs when cells in the arterial wall migrate into the stent and block blood flow.

“The results are what everyone was hoping for. Drug-eluting stents should now be considered the standard of care for most patients with restenosis of previously implanted bare metal stents, and radiation treatment should be abandoned,” says the study’s principal investigator Gregg Stone, M.D., professor of medicine, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/Columbia, and vice chairman of the Cardiovascular Research Foundation.

Millions of people have received bare metal stents in the past few years and hundreds of thousands are expected to experience restenosis. When restenosis cannot be controlled, patients are referred for bypass surgery. “Drug-eluting stents should significantly reduce the need for surgery in many thousands of patients,” Dr. Stone says.

The trial was sponsored and funded by Boston Scientific Corp.