Healthy News for Healthy Nation

Human hair cells. (Credit: Image courtesy of University of Virginia Health System)

Researchers at the University of Virginia Health System have discovered a way to transfer genes, which they hope will restore hearing, into diseased tissue of the human inner ear. This important step brings scientists closer to curing genetic or acquired hearing loss.

Dr. Jeffrey Holt, associate professor of neuroscience and otolaryngology at UVa, and his research team, including Dr. Bradley Kesser, an assistant professor of otolaryngology, targeted a gene known as KCNQ4, which causes genetic hearing loss in humans when mutated. They engineered a correct form of the gene and created a gene therapy delivery system that successfully transferred the KCNQ4 gene into human hair cells harvested from the inner ears of patients with hearing loss.

“Our results show that gene therapy reagents are effective in human inner ear tissue. Taken together with the results from another group of scientists who showed that similar gene therapy compounds can produce new hair cells and restore hearing function in guinea pigs suggest that the future of gene therapy in the human inner ear is sound,” Holt said.

Hair cells have hair-like projections that line the cochlea. In people with normal hearing, hair cells convert sound into electrical signals, which are ultimately transmitted to the brain. People with hearing loss suffer from too few, damaged or missing hair cells. Holt’s past research uncovered the speed at which hair cells develop in mouse embryos, a finding necessary to help researchers learn how to regenerate hair cells. With this current development, Holt and his team could one day restore the hearing process in damaged hair cells.

“This is a critically important step forward. We hope this breakthrough will propel the field of hearing and deafness research toward our collective goal of curing genetic and acquired deafness,” Holt said.

This discovery will appear Thursday, June 14, in the online issue of Gene Therapy.

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Computer model of AIDS virus (HIV). (Credit: Produced by Richard Feldmann; courtesy of NIH/National Institute of Allergy and Infectious Diseases)

A Canada-U.S. research team has solved a major genetic mystery: How a protein in some people’s DNA guards them against killer immune diseases such as HIV. In an advance online edition of Nature Medicine, the scientists explain how the protein, FOX03a, shields against viral attacks and how the discovery will help in the development of a HIV vaccine.

“HIV infection is characterised by the slow demise of T-cells, in particular central memory cells, which can mediate lifelong protection against viruses,” said lead researcher Rafick-Pierre Sékaly, a Université de Montréal professor and a researcher at the Centre Hospitalier de l’Université de Montréal and the French Institut national de la santé et de la recherche médicale (Inserm).

“Our group has found how the key protein, FOX03a, is vital to the survival of central memory cells that are defective in HIV-infected individuals even if they are treated,” added Dr. Sékaly, who produced his study with CHUM and Inserm colleagues including Elias El Haddad and Julien van Grevenynghe. Collaborators also included Jean-Pierre Routy, a McGill University Health Centre researcher and professor at McGill University and Robert S. Balderas, Vice-President of Research and Development at BD Biosciences of San Diego, CA.

Public support for the research came through Genome Canada and Génome Québec, among others, while private contributions came via a segment of BD (Becton, Dickinson and Company). “Public-private collaborations such as this play an important role in advancing medical research,” Robert S. Balderas. “BD Biosciences was pleased to provide powerful research instruments, reagents and technical expertise to support this breakthrough research.”

The breakthrough emerged by studying three groups of men: One HIV-negative sample, a second HIV-positive group whose infection was successfully controlled through tritherapy and a third group whose HIV did not show any symptoms. Called elite controllers, this third group fended off infection without treatment because their immune system, which would normally be attacked by HIV, maintained its resilient immune memory through the regulation of the FOX03a protein.

“Given their perfect resistance to HIV infection, elite controllers represent the ideal study group to examine how proteins are responsible for the maintenance of an immune system with good anti-viral memory,” said Dr. Haddad. “This is the first study to examine, in people rather than animals, what shields the body’s immune system from infection and to pinpoint the fundamental role of FOX03a in defending the body.”

Beyond HIV treatment, Dr. Sékaly said his team’s discovery offers promise for other immune diseases. “The discovery of FOX03a will enable scientists to develop appropriate therapies for other viral diseases that weaken the immune system,” he said, citing cancer, rheumatoid arthritis, hepatitis C, as well as organ or bone marrow transplant rejection.

Paul L’Archevêque, president and CEO of Génome Québec, lauded Dr. Sékaly’s team for their breakthrough and the people who volunteered for the study. “This discovery, the first such study in humans, is a major step forward in the understanding of how our immune system responds to life-threatening infections such as HIV. This advance stems directly from research co-financed by Génome Québec, which demonstrates the impact that genomic research can have in improving healthcare.”

This research was made possible by public and private institutions across Canada, the United States and France: the Université de Montréal, CHUM, Inserm, MUHC, Genome Canada, Génome Québec, Fonds de la recherche en santé du Québec, Canadian Institutes of Health Research, National Institutes of Health and BD Biosciences.

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HI-Virus leaving a cell. (Credit: NIH)

Impaired brain function is a prominent and still unsolved problem in AIDS. Shortly after an individual becomes infected with HIV, the virus can invade the brain and persist in this organ for life. Many HIV-infected individuals experience disturbances in memory functions and movement, which can progress to serious dementia. How the virus causes brain disease is still unclear.

Dr. Ruth Brack-Werner and her team at the Institute of Virology of the German Research Center for Environmental Health previously demonstrated that HIV invades not only brain macrophages but also astrocytes. Astrocytes are the most abundant cells in the brain. They perform many important activities which support functions of nerve cells and protect them from harmful agents. HIV-infected astrocytes normally restrain the virus and prevent its production. However, various factors can cause astrocytes to lose control over the virus, allowing the virus to replicate and to reach the brain. There HIV can infect other brain cells as well as immune cells that patrol the brain and may carry the virus outside the brain.

Thus astrocytes form a reservoir for HIV in infected individuals and represent a serious obstacle to elimination of the virus from infected individuals. Whether this also applies to other types of brain cells was unclear until now. In a study recently published in AIDS, Dr. Brack Werner, together with Ina Rothenaigner and colleagues present data indicating that neural progenitor cells can also form HIV reservoirs in the brain. Neural progenitor cells are capable of developing into different types of brain cells and have an enormous potential for repair processes in the brain.

Dr. Brack-Werner’s team used a multi-potent neural progenitor cell line, which can be grown and developed to different types of brain cells in the laboratory, for their studies. After exposing these neural progenitor cells to HIV, they examined the cultures for signs of virus infection for 115 days. HIV was found to persist in these cultures during the entire observation period.

The cultures released infectious HIV particles for over 60 days and contained information for production of HIV regulatory proteins- Tat, Rev and Nef- for even longer. Dr. Brack-Werner and her team also examined neural progenitor cell populations cells with persisting HIV for differences from uninfected cells. They found that HIV persistence had an influence on the expression of selected genes and on cell morphology, but did not prevent their development to astrocytes. Thus HIV persistence has the potential to change neural progenitor cells.

Dr. Brack-Werner’s summarizes, “Our study indicates that neural progenitor cells are potential reservoirs for HIV and that HIV persistence has the potential to change the biology of these cells.” In future studies the researchers are planning to investigate the influence of HIV infection on important functions of neural progenitor cells. These include migration to diseased regions of the brain and development of different types of brain cells. Subsequently they will investigate how HIV changes neural progenitor cells and, importantly, how to protect neural progenitor cells from harmful effects of the virus in HIV infected individuals.

Journal reference: Rothenaigner, I., Kramer, S., Ziegler, M., Wolff, H., Kleinschmidt, A., Brack-Werner, R. (2007): Long-term HIV-1 infection of neural progenitor populations. AIDS 21:2271–2281.

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A new CDC study estimates that one in four young women between the ages of 14 and 19 in the United States — or 3.2 million teenage girls — is infected with at least one of the most common sexually transmitted diseases. (Credit: iStockphoto/Roman Kazmin)

A new CDC study estimates that one in four (26 percent) young women between the ages of 14 and 19 in the United States – or 3.2 million teenage girls – is infected with at least one of the most common sexually transmitted diseases (human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis). The study, presented today at the 2008 National STD Prevention Conference, is the first to examine the combined national prevalence of common STDs among adolescent women in the United States, and provides the clearest picture to date of the overall STD burden in adolescent women.

Led by CDC’s Sara Forhan, M.D., M.P.H., the study also finds that African-American teenage girls were most severely affected. Nearly half of the young African-American women (48 percent) were infected with an STD, compared to 20 percent of young white women.

The two most common STDs overall were human papillomavirus, or HPV (18 percent), and chlamydia (4 percent). Data were based on an analysis of the 2003-2004 National Health and Nutrition Examination Survey.

“Today’s data demonstrate the significant health risk STDs pose to millions of young women in this country every year,” said Kevin Fenton, M.D., director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “Given that the health effects of STDs for women – from infertility to cervical cancer – are particularly severe, STD screening, vaccination and other prevention strategies for sexually active women are among our highest public health priorities.”

“High STD infection rates among young women, particularly young African-American women, are clear signs that we must continue developing ways to reach those most at risk,” said John M. Douglas, Jr., M.D., director of CDC’s Division of STD Prevention. “STD screening and early treatment can prevent some of the most devastating effects of untreated STDs.”

CDC recommends annual chlamydia screening for sexually active women under the age of 25. CDC also recommends that girls and women between the ages of 11 and 26 who have not been vaccinated or who have not completed the full series of shots be fully vaccinated against HPV.

The study of STDs among teenage girls is one of several presented March 11 at the 2008 National STD Prevention Conference that highlights the significant burden of STDs among girls and women, and identifies creative prevention strategies for reducing the toll of STDs in the United States.

Contraceptive services represent missed opportunities for STD screening, prevention

Two other studies featured at the conference point to missed opportunities for STD testing, and underscore that it is critical for STD screening to be included in comprehensive reproductive health services for young women.

A study by CDC’s Sherry L. Farr and colleagues found that while the majority of sexually active 15- to-24 year-old young women (82 percent) receive contraceptive or STD/HIV services, few receive both (39 percent). In addition, only 38 percent of a subset of young women who reported receiving contraceptive services associated with unprotected sex (e.g., pregnancy testing) also received STD/HIV counseling, testing or treatment, which indicates that many women at high risk are not receiving necessary prevention services.

A separate study, by CDC’s Shoshanna Handel and the New York City Department of Health and Mental Hygiene, examined STD screening rates among young women seeking emergency contraception, which would suggest recent unprotected sex. The study found that just 27 percent were screened for chlamydia or gonorrhea. A significant proportion of those women (12 percent) had a positive test result, highlighting the need for routine chlamydia and gonorrhea screening at emergency contraception visits.

Innovative programs provide models for effective STD prevention

Other research from the conference highlighted creative programs that are effectively screening and treating people with STDs, and identifying those most at risk.

A CDC-funded confidential chlamydia screening program in high school-based health clinics in California resulted in high rates of screening among those seeking contraceptive or STD services (range: 85-94 percent). It also revealed significantly higher infection rates among African-American women than white women (9.6 percent versus 1.7 percent).

A study by New York City health officials assessed the effectiveness of an express visit option, allowing patients at city clinics to be tested for STDs without a doctor’s exam. Comparing data before and after express visits were routinely offered, researchers found that the express visit option made it possible for an additional 4,588 tests to be performed, and increased STD diagnoses by 17 percent (2,617 versus 2,231).

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