April 16, 2013

Beet Juice Beats Hypertension

By Nancy Walsh, Staff Writer, MedPage Today

Published: April 15, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Drinking a cup of nitrate-rich beetroot juice significantly lowered blood pressure (BP) in hypertensive individuals, a small, proof-of-principle study showed.

Three to 6 hours after a single dose of 250 mL of beetroot juice, systolic BP decreased by a mean 11.2 mm Hg in patients with hypertension compared with a decrease of 0.7 mm Hg in controls, according to Amrita Ahluwalia, PhD, of Queen Mary University of London, and colleagues.

At 24 hours, systolic BP remained significantly lower in the treatment group compared with controls, with a difference of 8.5 mm Hg (P<0.01), the researchers reported in Hypertension: Journal of the American Heart Association.

Recent studies have suggested that the health benefits of fruits and vegetables in the diet may derive from the presence of inorganic nitrate (NO3), which is found in particularly high levels in beetroot and leafy vegetables.

Following consumption, NO3 is bioactivated by conversion to inorganic nitrite (NO2), which in turn is reduced to nitric oxide (NO) through various pathways, resulting in vasodilation.

In experiments conducted in both animals and healthy volunteers, high doses of nitrite lowered BP, but neither the specific enzymatic process nor its precise location -- in the vessel wall or the erythrocyte -- has been identified.

To expand the understanding of the physiologic effects of nitrite, Ahluwalia's group first conducted a series of experiments comparing the effects of nitrite administration in hypertensive and normotensive rats. They determined the reductase pathway responsible for nitrite conversion involved xanthine oxidoreductase (XOR) and established the erythrocyte as the site of nitrite reduction in hypertension.

In addition, the administration of allopurinol blocked these effects in the hypertensive animals, but had no effect in the normotensive animals.

The subsequent proof-of-principle study included 15 participants with BPs above 140/90 who had not previously received antihypertensive therapy.

The group consisted of eight women and seven men whose mean age was 53 and who received a relatively low (13.2 × 10−3 mol/L) dose of nitrite in beetroot juice or an equivalent amount of water containing nitrite levels of 0.07 × 10−3 mol/L.

The dose of nitrite in the beetroot group had previously shown little effect on BP in healthy volunteers, the researchers noted.

Significant decreases in both systolic and diastolic BPs occurred in participants receiving beetroot juice compared with controls (P<0.001), with diastolic pressures showing a peak lowering of 9.6 mm Hg.

Pulse wave velocity also fell significantly (P<0.05) in those receiving the juice.

Changes in systolic BP correlated with change in plasma nitrite levels (r=0.280, P<0.001), and decreases correlated with baseline systolic BP (r=0.561, P<0.05).

As with the animal studies, the erythrocyte was the site of bioactivity, with high levels of XOR expression and inhibition by allopurinol being observed.

In discussing their findings, the researchers noted that circulating levels of nitrate and nitrite had returned to normal 24 hours after administration, yet BP reductions persisted.

"It is possible that while circulating nitrite levels have diminished, tissue levels remain elevated providing a continued supply of NO, although further mechanistic studies exploring this possibility are warranted," they wrote.

The study demonstrated that BP lowering occurs with nitrite administration most strongly in hypertensive animals and humans and could represent a therapeutic option, they concluded.

The study participants tolerated the regimen well.

"This is a natural compound, and is quite innocuous," said William O'Neill, MD, of Henry Ford Hospital in Detroit, who was not involved in the study.

But O'Neill cautioned against the use of beetroot juice by patients with renal failure.

"I'm not sure what's going to happen to potassium levels in the bloodstream if they have renal insufficiency," he told MedPage Today.

"Given that approximately 50% of treated hypertensive subjects fail to achieve their target BP, an additional strategy, based on intake of nitrate-rich vegetables, may prove to be cost-effective, easily achievable, safe, and favorable for public health," they noted.

A limitation of the study was its short duration, and further work will be needed to determine if long-term dietary increases in nitrite-containing foods can lead to sustained BP lowering.

The study was funded by the British Heart Foundation.

The lead author and one co-author are directors of Heartbeet.

From the American Heart Association:

Dietary Approaches to Prevent and Treat Hypertension

Primary source: Hypertension
Source reference:
Ahluwalia A, et al "Enhanced vasodilator activity of nitrite in hypertension: critical role for erythrocytic xanthine oxidoreductasse and translational potential" Hypertension 2013; DOI: 10.1161/​HYPERTENSIONAHA.111.00933.

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ART for HIV May Protect Against HBV

Reuters Health Information

 

Apr 11, 2013

By David Douglas

NEW YORK (Reuters Health) Apr 11 - In a study of men with HIV, antiretroviral therapy (ART) with lamivudine or tenofovir disoproxil fumarate (TDF) appeared to protect against infection with hepatitis B virus (HBV), Japanese researchers say.

Dr. Hiroyuki Gatanaga of the National Center for Global Health and Medicine, Tokyo and colleagues evaluated stocked serum samples from HIV-infected men who have sex with men.

They found a lower frequency of incident HBV infection under lamivudine- and TDF-containing ART than under ART without lamivudine and TDF, or without ART at all, Dr. Gatanaga told Reuters Health by email, adding that "HBV-active ART seems to work as a pre-exposure prophylaxis against HBV."

As reported March 13th online in Clinical Infectious Diseases, the research team had access to "first stocked blood samples" from 1,434 HIV-infected men who hadn't been vaccinated against HBV; 354 were negative for all analyzed HBV serological markers.

During follow-up of the latter group, analysis of their last samples indicated HBV incident infection in 43 (12.1%).

Rates of incident infections per 100 person-years were 0.669 during lamivudine- or TDF-containing ART, 6.726 with no ART, and 5.263 with some other type of ART.

However, it seems that lamivudine-resistant strains may evade the drug's protective effect. These infections were more prevalent during ART with lamivudine (50%) than during no or other ART (7.1%).

In fact, Dr. Gatanaga added, "In order to prevent lamivudine-resistant HBV infection, TDF-ART should be used instead of (lamivudine)-ART."

Also, Dr. Gatanaga pointed out, "Some doctors are trying to use a NRTI-sparing regimen because they want to avoid NRTI toxicity such as mitochondrial damage. But NRTI-sparing regimens do not have HBV-prophylactic effects."

Dr. Gatanaga believes the same prophylactic effects should also work in women.

SOURCE: http://bit.ly/156fkzy

Clin Infect Dis 2013.

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-- Benitec progresses hepatitis C therapeutic towards the clinic

-- Application for RAC review of hepatitis C clinical trial protocol received by NIH

-- Application expected to be considered at the June RAC meeting

SYDNEY, April 16, 2013 /PRNewswire/ -- RNAi-based therapeutics company Benitec Biopharma Limited (ASX Code: BLT) today announced that the company's wholly owned US subsidiary, Tacere Therapeutics Inc., has submitted an application to the US National Institutes of Health's Recombinant DNA Advisory Committee (RAC) .

The RAC submission document comprises the full clinical trial protocol for its first-in-man ddRNAi-based therapeutic (TT-034) for hepatitis C virus (HCV) infection, as well as the safety and toxicology data and responses to questions concerning the objective and rationale for the proposed trial. Most of this material will be utilised in the subsequent US Food and Drug Administration (FDA) Investigational New Drug (IND) application for TT-034.

The RAC review is a required step for a product that involves gene therapy vectors before a clinical trial can be initiated. The RAC process results in recommendations that are disseminated to various bodies, including the Company and the FDA. The review can be administrative or include a public hearing. If the application is subject to a hearing, this is expected to be part of the next RAC meeting in June 2013.

David Suhy, Ph.D., Tacere's US-based, Senior Vice President of Research and Development commented, "Completing this submission is an important step in moving TT-034 into the clinic. We look forward to receiving the Committee's recommendations and then moving ahead with an IND and initiating the clinical trial for TT-034 this year. It has been very gratifying to oversee the development of a first-in-class therapeutic from concept to the clinic."

About TT-034

TT-034 is a potentially transformative therapeutic that is intended to provide a "one-shot-cure" for hepatitis C with a single injection. Preclinical studies have shown that the vector used to deliver TT-034 specifically targets liver cells where it transfects almost every cell without causing toxic effects. TT-034 is designed to prevent development of viral resistance (a major problem for most hepatitis C drugs) by simultaneously silencing three separate highly conserved regions on the virus genome. Studies have demonstrated that a single treatment of TT-034 is active out to 180 days (the duration of the studies).

About Benitec Biopharma Limited:

Benitec Biopharma Limited (ASX Code: BLT), based in Sydney, Australia, has a pipeline of in-house and partnered therapeutic programs based on its patented gene-silencing technology, ddRNAi. Benitec is developing treatments for a range of chronic and life-threatening human conditions. Benitec has licensed its ddRNAi technology to other biopharmaceutical companies who are advancing their programs toward the clinic for applications including HIV/AIDS, retinitis pigmentosa and Huntington's disease. For more information on Benitec refer to the Company's website at www.benitec.com.

For more information please contact:

Dr Peter French|Chief Executive Officer
Phone: +61 (02) 9555 6986 | pfrench@benitec.com | www.benitec.com

SOURCE Benitec Biopharma Limited

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http://www.benitec.com

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Scarring May Raise Death Risk From Fatty Liver Disease

Study looked at liver condition not tied to alcoholism

TUESDAY, April 16 (HealthDay News) -- Advanced fibrosis -- or progressive scarring of the liver -- is tied to higher death rates from a type of fatty liver disease found in people who drink little or no alcohol, according to a new study.

This increased mortality is primarily due to heart-related causes, not nonalcoholic fatty liver disease alone, the researchers said. The study was published in the April issue of the journal Hepatology.

"Our findings confirm that [nonalcoholic fatty liver disease] patients without advanced fibrosis do not have higher mortality risk," lead study investigator Dr. W. Kim Ray, of the Mayo Clinic in Rochester, Minn., said in a journal news release. "Careful monitoring of disease progression in patients with [nonalcoholic fatty liver disease] and fibrosis, along with interventions that reduce cardiovascular risk factors, are warranted."

The study involved data on more than 11,000 people from a large national survey compiled by the U.S. National Center for Health Statistics and the U.S. Centers for Disease Control and Prevention from 1988 to 1994. Researchers also included follow-up data on deaths through 2006.

Thirty-four percent of the participants had nonalcoholic fatty liver disease. Of these people, 72 percent did not have significant scarring or fibrosis. Meanwhile, 3 percent were affected by advanced fibrosis.

Although nonalcoholic fatty liver disease was not linked to an increase in death rates after 15 years, mortality increased as scarring progressed. The patients with advanced scarring had a 69 percent increase in mortality compared with those without scarring of the liver.

Nonalcoholic fatty liver disease was diagnosed by ultrasound. Fibrosis scores were used to rate the severity of organ scarring.

"The effect of [nonalcoholic fatty liver disease] on public health is not well understood," Ray said. "Large, population-based studies, which can provide insight into disease activity, present some difficulty given that liver biopsy is required to confirm [nonalcoholic fatty liver disease]."

As obesity rates have doubled in the United States during the past 25 years, so has the incidence of nonalcoholic fatty liver disease, making it the most prevalent liver disease in the United States, according to the news release.

More information

The American Liver Foundation has more about nonalcoholic fatty liver disease.

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New technique to deliver life-saving drugs to the brain

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PRESS RELEASE

April 16, 2013, 12:09 p.m. EDT

MIAMI, April 16, 2013 /PRNewswire-USNewswire/ -- In a study published in today's issue of Nature Communications, researchers from Florida International University's Herbert Wertheim College of Medicine describe a revolutionary technique they have developed that can deliver and fully release the anti-HIV drug AZTTP into the brain.

Madhavan Nair, professor and chair, and Sakhrat Khizroev, professor and vice chair of the HWCOM's Department of Immunology, used magneto-electric nanoparticles (MENs) to cross the blood-brain barrier and send a significantly increased level of AZTTP--up to 97 percent more --to HIV-infected cells.

For years, the blood-brain barrier has stumped scientists and doctors who work with neurological diseases. A natural filter that allows very few substances to pass through to the brain, the blood-brain barrier keeps most medicines from reaching the brain. Currently, more than 99 percent of the antiretroviral therapies used to treat HIV, such as AZTTP, are deposited in the liver, lungs and other organs before they reach the brain.

"This allows a virus, such as AIDS, to lurk unchecked," said Nair, an HIV/immunology researcher.

The patent-pending technique developed by FIU binds the drug to a MEN inserted into a monocyte/macrophage cell, which is then injected into the body and drawn to the brain. Once it has reached the brain, a low energy electrical current triggers a release of the drug, which is then guided to its target with magnetoelectricity. In lab experiments, nearly all of the therapy reached its intended target. It will soon enter the next phase of testing. For visuals please click here.

Potentially, this method of delivery could help other patients who suffer from neurological diseases such as Alzheimer's, Parkinson's, epilepsy, muscular dystrophy, meningitis and chronic pain. It could also be applicable to diseases such as cancer.

"We see this as a multifunctional therapy," said Khizroev, who is an electrical engineer and physicist by training.

Multi-disciplinary efforts that combine principles of those fields with immunology enabled the project to move forward.

"The success of our nanotechnology is derived from the fact that nature likes simplicity," Khizroev said.

Media Contact: Robyn Nissim

305-348-1061

News.fiu.edu

SOURCE Florida International University

Web site: http://fiu.edu/

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FDA Approves FibroScan® for Non-invasive Liver Diagnosis

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PARIS, April 16, 2013 /PRNewswire/ --

- Echosens™ is pleased to announce that FibroScan® device received 510(k) clearance from the U.S. Food and Drug Administration (FDA) on April 5th, 2013 and is now ready to market its pioneering technology in the United States.

Today, 1800 FibroScan® devices are used worldwide both in research and routine clinical practice. The United States of America is the last major market to approve FibroScan®.

(Logo: http://photos.prnewswire.com/prnh/20130415/607780-a )

(Photo: http://photos.prnewswire.com/prnh/20130415/607780-b )

FibroScan® is used in the clinical management of patients with liver disease such as chronic viral hepatitis C and B and fatty liver diseases. Based on a technology called transient elastography, FibroScan® assesses liver shear wave speed (expressed in meter per second) and equivalent stiffness (expressed in kilopascal) at 50 Hz in a rapid, simple, non-invasive and totally painless way.

Initially introduced in the European market in 2003, FibroScan® pioneered the quantitative elastography medical field. It received market clearances in China (2008), Canada (2009), Brazil (2010), Japan (2011) and is currently available in 70 countries.

With more than 660 peer-reviewed publications, FibroScan® is by far the elastography device with the largest body of evidence on its clinical usefulness. Moreover, the use of FibroScan® is also mentioned in guidelines and recommendations in different regions of the world: World Health Organization, European Association for the Study of Liver (EASL), Asian Pacific Association for the Study of Liver (APASL), etc.

FibroScan® is manufactured by Echosens™ (Paris, France). Since its foundation in 2001, Echosens™ has gathered strong leadership in quantitative elastography. Very active in research and development, Echosens™ holds 17 patent families mainly focused on its core technology: Vibration-Controlled Transient Elastography (VCTE™).

Contact Echosens™:
Aurélie Houet, Communication Manager
Tel: +33-1-44-82-78-50
Email: aurelie.houet@Echosens.com
http://www.echosens.com

SOURCE Echosens

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SYDNEY, April 15, 2013 /PRNewswire/ -- RNAi-based therapeutics company Benitec Biopharma Limited (ASX Code: BLT) today announced the selection of the University of California, San Diego (UCSD), Health Sciences as the second site for its upcoming phase I/II first-in-man trial for TT-034 in Hepatitis C infections (HCV). Benitec previously announced the selection of Duke Clinical Research Unit as the other site. TT-034 is being developed as a potential "one-shot-cure" for HCV.

A consultant and sub-principal investigator for the study from UCSD Health Sciences will be Robert Gish, M.D., clinical professor of Medicine and medical director of Hepatology. Dr. Gish is a renowned hepatitis researcher with previous experience using RNAi based therapeutics for HCV. He has over 500 publications in the field and is a fellow of the American College of Physicians and the American Association for the Study of Liver Disease.

"I look forward to working with Benitec and Duke University on this important program," Dr. Gish commented. "This is the first time that this therapeutic modality is being tested in humans, and if it is successful I believe it can be a significant step forward, not only for HCV treatment but potentially also as a treatment modality for Hepatitis B."

The principal investigator for the study at UC San Diego is David Wyles, M.D., associate professor of Medicine at the UC San Diego AntiViral Research Center, the clinical research site that will be conducting the trial. His research interests include the laboratory evaluation of new antiviral therapies for HCV, drug resistance to HCV antivirals, and HCV viral fitness.

Peter French, Ph.D., chief executive officer of Benitec said, "We are elated that UC San Diego and Dr. Gish will participate in this study. We now have two top clinical research teams working with Benitec on this trial. This constellation of expertise will greatly benefit our HCV program and can help demonstrate the power of our ddRNAi technology in the clinic. Having our two clinical centers in place moves us a step closer to initiating the Phase I/II clinical trial, which we expect to occur during the second half of 2013."

The phase I/II clinical trial is an open-label dose escalation study to evaluate the safety and activity of single doses of TT-034 in patients with chronic HCV genotype 1 infection who have failed previous treatments. The trial is expected to involve 14 patients in 5 sequential dose cohorts. Additional consolidation cohorts may be added during the study to confirm the results of the trial. The primary safety endpoints are dose limiting adverse events. The primary end points are serum viral load reduction and degree of hepatocyte transduction (measured through liver biopsies). There is a pre-specified interim read on safety and activity within months of trial commencement.

About TT-034

TT-034 is a potentially transformative therapeutic that is intended to provide a "one-shot-cure" for Hepatitis C with a single injection. TT-034 works through RNA interference (RNAi), which is a naturally occurring regulatory process in cells that acts to "silence" genes after they have been transcribed from DNA into messenger RNA. Benitec's proprietary ddRNAi approach involves the introduction of a DNA vector that produces short hairpin RNAs (shRNAs) that are processed by the cell into siRNAs. This approach emulates the cell's own gene silencing mechanism and provides long term activity (months). Moreover, the virus vector used to deliver the TT-034 construct, an engineered non-replicating adeno-associated virus (AAV8), targets almost exclusively liver cells (where HCV replicates). TT-034 is further designed to prevent viral escape through mutations (a major problem for most HCV drugs) by using three different shRNAs to simultaneously target three separate highly conserved regions in the HCV genome. In mice and monkeys, TT0-034 has been shown to transduce 100% of hepatocytes in the liver and provide high shRNA activity for 180 days (the duration of the studies), without adverse effects.

About UC San Diego Health Sciences

University of California, San Diego Health Sciences comprises clinical and academic entities -- UC San Diego Health System, the region's only academic health system; UC San Diego School of Medicine, one of the top US research-intensive schools of medicine; and Skaggs School of Pharmacy and Pharmaceutical Sciences. The US National Institutes of Health (NIH) ranks UC San Diego Health Sciences as one of the top institutions in research funding per faculty member, and the School of Medicine is in the top 10 in total NIH research funding. Part of the University of California system, UC San Diego -- founded in 1960 -- is renowned for collaborative and cross-disciplinary research that transcends traditional boundaries in science, engineering and the humanities.

About Benitec Biopharma Limited:

Benitec Biopharma Limited (ASX Code: BLT), based in Sydney, Australia, has a pipeline of in-house and partnered therapeutic programs based on its patented gene-silencing technology, ddRNAi. Benitec is developing treatments for chronic and life-threatening human conditions. Its most advanced program is TT-034 for the treatment of chronic HCV infection. Benitec has licensed ddRNAi technology to other biopharmaceutical companies who are advancing their programs toward the clinic for applications including HIV/AIDS, retinitis pigmentosa and Huntington's disease. For more information on Benitec refer to the Company's website at www.benitec.com.

For more information please contact:

For UCSD:

Ms. Jackie Carr, Communications Director, UCSD Health System

Phone: +1-619-543-6163. jcarr@ucsd.edu. http://som.ucsd.edu

For Benitec:

Dr. Peter French, Chief Executive Officer

Phone: +61 (02) 9555 6986. pfrench@benitec.com. www.benitec.com

SOURCE Benitec Biopharma Limited

Web site: http://www.benitec.com

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Also See: HCV "One-Shot-Cure" ddRNAi Therapy Study Starting

LONDON, April 16, 2013 /PRNewswire/ --

Antibody Treatment for HIV

SEEK, a privately-owned UK drug discovery group, announces that pre-clinical results on its HIV immunotherapy have been published in the peer-reviewed journal Virology Journal.

SEEK's HIV immunotherapy triggers the immune system's cellular and antibody responses to selectively identify and kill HIV infected cells. The most exciting aspect of this therapy is that it directs the immune system towards short highly conserved regions of proteins produced by most circulating HIV strains. The triggered immune responses are highly effective both independently and in combination.

This opens up developing the antibody response into a monoclonal based therapy for treating HIV.

Monoclonal antibodies have revolutionised the treatment of cancer by improving outcomes and survival. In HIV/AIDS there is new interest in these products, as shown by the recent work of Duke University (USA) in developing a monoclonal antibody that prevents the virus from infecting cells. A monoclonal antibody capable of killing HIV-infected cells (potentially curative effect) would represent a radical new development in HIV therapy, which to this day relies on slowing down the virus rate of growth rather than in killing the cells that harbour it.

By targeting a HIV component that is found only in infected cells and never in healthy cells, such monoclonal antibody therapy offers the potential of high specificity, reduced frequency of administration and minimal side-effects. This would represent a significant improvement over current anti-HIV drugs which require daily treatment and are associated with significant side effects.

Commenting on today's announcement, Gregory Stoloff, CEO of SEEK Group, said: "It is very exciting to be at the forefront of this new approach which opens up HIV therapy to established and available antibody technology."

The manuscript: Olga Pleguezuelos, Gregory A Stoloff and Wilson Caparros-Wanderley, 'Synthetic immunotherapy induces HIV virus specific Th1 cytotoxic response and death of an HIV-1 infected human cell line through classic complement activation', Virology Journal 2013, 10:107, can be found at the following URL:

http://www.virologyj.com/content/10/1/107

In July 2011, SEEK announced the results of a Phase Ib/II study in humans which demonstrated that HIV immunotherapy showed a one log (approx 90 percent) difference in viral count in HIV-infected people compared with the placebo group, after just a single administration.

About SEEK

Founded in 2004, SEEK (previously known as PepTcell) is privately-owned and funded, with headquarters in London, UK. SEEK brings safe and low costs medicines to the patients as quickly as possible. It does this by modifying existing medicines to improve their efficacy within current label, dose and regime, by changing the indication but keeping the dose and dosing regime the same or by creating a new medicine when the previous options are unavailable.

Additional information about SEEK is available on the Company's website located at http://www.seekacure.com

For more information please contact:

Gregory Stoloff, CEO, SEEK

Tel +44(0)20-7153-6570

M:Communications

Mary Clark / Amber Bielecka / Hollie Vile

Tel +44(0)20-7920-2330

seek@mcomgroup.com 

SOURCE SEEK

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Circumcision study supports HIV theory

Researchers say the foreskin can shelter troublesome bacteria, so its removal may bolster the immune system to keep the AIDS virus at bay.

By Monte Morin, Los Angeles Times

April 15, 2013, 11:16 p.m.

Circumcision is known to reduce a man's risk of HIV infection by at least half, but scientists don't know why. A new study offers support for the theory that removing the foreskin deprives troublesome bacteria of a place to live, leaving the immune system in much better shape to keep the human immunodeficiency virus at bay.

Anyone who has ever lifted a rock and watched as the earth beneath it was quickly vacated by legions of bugs and tiny worms would be familiar with the principle, said study leader Dr. Cindy Liu: After the foreskin is cut away, the masses of genital bacteria that once existed beneath it end up disappearing.

"It's the same as if you clear-cut a forest," said Liu, a pathologist at the Translational Genomics Research Institute in Flagstaff, Ariz. "The community of animals that once lived in that forest is going to change."

Of particular note is that circumcision undercuts anaerobic bacteria, the microbes that thrive in oxygen-deprived environments, she said. By reducing the number of anaerobic bacteria, the body's immune cells may be better able to destroy the virus — and less likely to fall prey to its Trojan horse-style of attack, the authors suggest.

Liu and her colleagues present their case in a paper published Tuesday in the journal mBio.

Numerous studies conducted over the last two decades have shown that male circumcision reduces the risk of HIV infection in men who have heterosexual intercourse by 50% to 60%. Some researchers have speculated that the foreskin is prone to tearing, giving the virus more routes of entry. Others have argued that removal of the foreskin simply reduces the surface area available to be infected.

Liu and coauthor Lance Price, a professor of environmental health sciences at George Washington University in Washington, suspected it had to do with the bacterial species that inhabit the coronal sulcus, the shallow groove behind the head, or glans, of the penis.

To establish a possible connection, study authors enrolled 156 Ugandan men in a randomized trial in which half of them were circumcised and the other half were not.

Study participants ranged in age from 15 to 49. While the prospect of undergoing circumcision as an adult might not appeal to many American men, 5,000 Ugandan males volunteered for the study. In a region where 1 in 6 people are infected with HIV, circumcision's "powerful potential" to reduce the risk of infection was strong motivation, said coauthor Dr. Aaron Tobian, a health epidemiologist and pathologist who teaches at Johns Hopkins University School of Medicine.

On average, there was an 81% reduction in bacteria in the circumcised men one year after surgery, the researchers reported. Some of the biggest drops were recorded for anaerobic bacteria, they said.

Bacteria on the coronal sulcus fell by more than 33% in the circumcised men, Liu said.

Interestingly, the men in the uncircumcised control group also experienced a reduction in bacteria, but not to the degree that the circumcised men did, Liu said. This was probably because of health and hygiene information that was given to all study participants.

"That's not an uncommon outcome," she said. "Just being in a trial can confer some benefits."

The study only examined the effect of circumcision on reducing or altering bacterial colonies on the penis. Further research must be done to draw a direct connection between these changes in the microbiome and subsequent HIV infection.

However, the study offers strong support for the idea that bacteria — particularly anaerobic bacteria — can cause inflammation that will trigger the body's immune system and summon a variety of cells to fight a threat. Among those fighters are T4 cells, which are infected by HIV. The virus needs those cells to survive and replicate over time.

The study authors argue that the large populations of bacteria in uncircumcised men attract these T4 cells, giving the virus a means of entry during intercourse with an infected person. However, circumcised men are much less likely to mobilize these susceptible cells; therefore, the virus can be destroyed by other types of immune cells.

Dr. Alexandra Levine, chief medical officer at the City of Hope Cancer Center in Duarte, said scientists have long been searching for the connection between circumcision and reduced HIV infection. The authors of the new study make a convincing argument, she said.

"This is an important paper in beginning to document what the reason might be," said Levine, who was not involved in the research. "Their data are convincing to me."

Price said that colleagues were already working on follow-up studies. If the connection can be proved, there might be less-invasive ways of altering bacterial populations that do not rely on circumcision.

"As a society, we've gotten used to thinking about alterations to the microbiome as having negative outcomes," said Price, who is married to study leader Liu. "We think about the person who takes antibiotics in the hospital and ends up with an infection in their gut because we've knocked out the natural microbiota. But here's a situation where we're flipping that notion on its head. The disturbance of the microbiome could have a positive effect."

monte.morin@latimes.com

Source

ACH

April 16, 2013

All-Oral Trial to Evaluate the Safety and Efficacy of a 12-Week Regimen of Sovaprevir, ACH-3102 and Ribavirin for Genotype 1 Treatment-Naive HCV Patients

NEW HAVEN, Conn., April 16, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that it has initiated an international Phase 2 clinical trial with sovaprevir and ACH-3102 for the treatment of genotype 1 chronic hepatitis C (HCV). The trial will evaluate an all-oral 12-week interferon-free regimen consisting of sovaprevir, ACH-3102, and ribavirin in patients with chronic HCV who have not received prior therapy.

"With the initiation of this study, Achillion embarks on an aggressive and robust Phase 2 program. In previous clinical trials, both sovaprevir and ACH-3102 were shown to be efficacious, safe, well-tolerated, and had demonstrated a high barrier to resistance. Hence, we believe that a combination of these two agents for the treatment of chronic hepatitis C has the potential to be well-tolerated and provide high SVR rates," commented Milind Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer of Achillion.

"Based upon the highly competitive SVR rates achieved to date with sovaprevir and the robust and unique single-agent activity observed with ACH-3102, our cornerstone NS5A inhibitor, we are optimistic about the results from this interferon-free trial," commented Michael Kishbauch, President and Chief Executive Officer of Achillion. "Achillion looks forward to reporting all-oral results from our ongoing clinical trials including RVR results from the -007 sovaprevir and ACH-3102 study during the third quarter of this year, as well as providing the updated SVR results later this month from our safety and tolerability study of ACH-3102 and ribavirin for the treatment of genotype 1b HCV."

Summary of Phase 2 '-007' Trial of Sovaprevir and ACH-3102

This is a Phase 2 trial which will evaluate the safety, tolerability and efficacy of 12 weeks of sovaprevir, ACH-3102 and ribavirin in up to 50 treatment-naïve patients with chronic genotype 1 HCV. Initially, 30 patients will be enrolled and randomized to receive either a combination of sovaprevir, ACH-3102 and ribavirin or matching placebos. Once daily 200 mg or 400 mg doses of sovaprevir with ACH-3102, given as a 150 mg loading dose followed by a 50 mg once daily dose, in combination with ribavirin, will be evaluated in this trial. Primary endpoints include safety, tolerability, and sustained virologic response 4 weeks after the completion of dosing (SVR4). The trial is expected to enroll patients at sites in the United States, Canada, New Zealand and Australia.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including more than 5 million people in the United States, more than twice as widespread as HIV. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000 begin_of_the_skype_highlighting 1-203-624-7000 end_of_the_skype_highlighting.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potency, safety, tolerability, effectiveness and other characteristics of sovaprevir and ACH-3102; and Achillion's expectations regarding timing for the commencement, completion and reporting of results of its -007 clinical trial of sovaprevir and ACH-3102 in combination with ribavirin, as well as with respect to other ongoing clinical studies. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage clinical trials of sovaprevir, ACH-3102 and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2012 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

CONTACT:

Company Contact: Glenn Schulman Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000  gschulman@achillion.com

Investors: Mary Kay Fenton Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000 mfenton@achillion.com

Media: Sally Barton Ogilvy PR Tel. (212)880-5240 sally.barton@ogilvy.com

Investors: Seth Lewis The Trout Group, LLC Tel. (646) 378-2952 slewis@troutgroup.com

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