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NIH funds new research toward an HIV cure
 
 
  5-year grants total $14 million in first year

Three research teams focused on developing strategies that could help to rid the body of HIV are receiving grants totaling more than $14 million a year, for up to five years, the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health announced today.

The grants are part of the Martin Delaney Collaboratory, a funding opportunity designed to foster public-private partnerships to accelerate progress toward an HIV cure. Delaney, an influential AIDS activist, died of liver cancer in 2009.

Although antiretroviral therapy enables many people infected with HIV to effectively control their virus levels and thereby stay relatively healthy, some virus remains hidden in a latent or persistent form in cells and tissues where it is not susceptible to antiretrovirals. Each research team will pursue a unique and complementary approach aimed at eradicating these remaining HIV reservoirs. To fulfill their role as members of a collaboratory, the teams will also meet periodically as their research progresses to find ways to work together.

"Martin Delaney was a true hero in the fight against HIV/AIDS, and he believed, as we do, that progress toward a cure for HIV/AIDS can be made through partnerships among scientists in government, industry and academia," said NIAID Director Anthony S. Fauci, M.D. "These new grants, and the collaboratory to which they belong, are one way in which we honor his memory and advance his vision."

The research teams receiving the grants include the following:

Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, working with Sangamo Biosciences Inc., a biopharmaceutical company based in Richmond, Calif.-In five projects led by co-principal investigators Keith R. Jerome, M.D., Ph.D., and Hans-Peter Kiem, M.D., of FHCRC, scientists will attempt to develop proteins that directly attack HIV reservoirs, and they also will study whether a patient's immune cells can be made resistant to the virus. These approaches for eliminating the viral reservoirs will be further tested in a preclinical model. Five core facilities will be funded as well, to provide shared resources and support services to facilitate the collaborative projects. First-year funding is $4.1 million.

University of North Carolina at Chapel Hill (UNC), working with Merck Research Laboratories, headquartered in Whitehouse Station, N.J.-Led by principal investigator David Margolis, M.D., of UNC, this initiative consists of 15 scientific projects and four core facilities located at multiple universities nationwide. The researchers aim to enhance the understanding of how HIV persists in patients on antiretroviral therapy, and to develop small-molecule drug candidates and other therapies to target the viral reservoirs. First-year funding is $6.3 million.

University of California, San Francisco (UCSF), and the Vaccine & Gene Therapy Institute of Florida (VGTI) in Port St. Lucie, Fla., also working with Merck Research Laboratories-Led by co-principal investigators Steven Deeks, M.D., and Michael McCune, M.D., Ph.D., of UCSF, and Rafick-Pierre Sekaly, Ph.D., of VGTI, this research initiative comprises seven projects and three core facilities. The researchers seek to define the nature and location of the cells where HIV hides, better understand the immunology of how these viral reservoirs are created and maintained, and develop and test targeted treatments that eliminate HIV reservoirs without broadly activating the immune system. First-year funding is $4.2 million.

NIAID is providing primary funding for the grants. Additional funding comes from the National Institute of Mental Health (NIMH), also part of NIH. Funding beyond the first year is subject to the availability of appropriations. Sangamo Biosciences and Merck Research Laboratories will not receive federal funds for their contribution to this research.

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Big Cure AIDS grant for UNC

The Chapel Hill-led group will get $32 million in effort to purge virus.


By Jay Price
jay.price@newsobserver.com
www.charlotteobserver.com
Posted: Tuesday, Jul. 12, 2011

"The additional funding for a cure, not just prevention or vaccination, shows "the NIH and the scientific community are saying that finding a cure for AIDS is a realistic goal and should be part of our plan of attack against the epidemic," said Dr. David Margolis, the project's lead researcher. The grant will be administered by the North Carolina Translational and Clinical Sciences Institute at UNC"

CHAPEL HILL A national consortium of researchers led by a team at UNC-Chapel Hill has won a major federal grant aimed at curing AIDS.

The group was awarded $32 million over five years to seek ways to cure HIV patients by eradicating hidden reservoirs in the immune systems of patients taking anti-retroviral drugs.

It's part of the first major funding initiative aimed at eliminating HIV, the virus that causes AIDS, from the cells and tissues of patients, said Dr. David Margolis, a professor in UNC's School of Medicine and its Gillings School of Global Public Health. He is the principal investigator for the group, which includes researchers from nine other universities.

Many who become infected with the virus can remain relatively healthy by using an elaborate and often expensive regimen of drugs that can block its effects.

But the virus itself never goes away. Instead, bits of its genetic material remain, dormant, in some cells and tissue, said Margolis, who specializes in microbiology, immunology and epidemiology. If a patient stops taking the drugs, the virus can become active again, infecting new cells.

The researchers will try find a way to locate those bits of HIV genetic material and then entirely purge them from the body.

"We're essentially trying to force the virus out into the open," Margolis said.

It's the largest of three related grants that were announced Monday by the National Institutes of Health's National Institute of Allergy and Infectious Diseases.

Seeking drug that works

Each consortium will take a different and complementary approach to attacking the reservoirs of the virus, said Nalini Padmanabhan, a spokeswoman for NIAID.

Between them, the three grants could eventually total $70 million if funding is available for all five years, she said.

The UNC-led effort will launch 15 research projects that, among other things, would try to discover how the virus can remain dormant and nearly undetectable, and to identify drugs and methods that can purge it from the body.

An unfunded partner in the grant is the pharmaceutical company Merck, which has development drugs and other therapies that target such reservoirs of virus.

The grant comes on the heels of an announcement in May that another UNC-CH-led group had found that the antiretroviral drugs used to treat HIV patients can be a strong barrier to spreading of the disease.

If a way to purge patients of the virus can be found, that could join such prevention methods to put HIV in a kind of squeeze play that could sharply reduce the impact of HIV/AIDS on society, Margolis said.

Lifting the burden

"We need to work from both ends," he said. "Prevention, and then in cases where we aren't able to prevent it, we need tools to eradicate the disease."

The current treatment regimens, he said, mean keeping patients alive, which is a good thing, but costly. Being able to cure patients entirely would lift that burden for society.

The new grants are unlikely to be enough to develop a cure, but they could provide a solid start, Margolis said.

"We hope to make concrete advances that can be measured, and that attract more funding," he said.

"You have to start somewhere, and we're really happy to be a part of the beginning of this."

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Big Bolus for HIV/AIDS Cure Research

news.sciencemag.org
by Jon Cohen on 11 July 2011,

Three collaborations will receive up to $70 million over the next 5 years to advance the search for an HIV/AIDS cure, the U.S. National Institutes Health (NIH) announced today. This is the largest single investment yet made into finding a way to rid the virus from the body or at least reduce levels to the point that infected people can stop taking anti-HIV drugs-which many researchers until recently viewed as a hopeless quest.

The three grant recipients of what's known as the Martin Delaney Collaboratory include teams organized by the University of North Carolina (UNC), Chapel Hill, the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, and the University of California, San Francisco (UCSF), working with the Vaccine & Gene Therapy Institute of Florida (VGTI) in Port St. Lucie, Florida. "The three collaboratories are using very different but largely complementary approaches," says UCSF's Steven Deeks, one of the principal investigators for that project. "Since many of us believe a cure will require combination therapy, it is my hope-as well as the hope of others-that three groups can merge their work whenever possible."

The best-funded and largest group, led by UNC's David Margolis, will receive $6.3 million per year for 15 different projects. The researchers will both conduct basic research and attempt to develop small molecule drugs that can reduce the reservoir of cells infected with latent HIV that stubbornly persist even in people who receive the best antiretroviral treatments available. The 19 collaborators Margolis leads come from nine universities across the country and the Merck Research Laboratories. "We're very excited to try and approach this important and complicated problem as a group," says Margolis

The other two collaborations will each receive a shade over $4 million per year. The UCSF and VGTI project, which is also with Merck, plans to use immune-based treatments in addition to small molecules to shrink reservoirs. Headed by VGTI's Rafick-Pierre Sekaly and UCSF's Deeks and Mike McCune, the project includes academic collaborators in Australia and Sweden.

The FHCRC project, led by Keith Jerome and Hans-Peter Kiem, involves two distinct but potentially complimentary approaches. One partners with California's Sangamo Biosciences and the City of Hope to create a bone marrow transplant that mimics the treatment given to Timothy Brown, aka the "Berlin patient" -- the first and only person who apparently has been cured of HIV/AIDS. (The case indeed helped catalyze the new interest in cure research, as this Science article details.) Specifically, they will engineer stem cells to cripple a key receptor the virus uses to infect cells and then transplant those cells into monkeys and, eventually, humans. The second strategy aims to deliver an enzyme called an endonuclease that specifically clips HIV DNA lurking in chromosomes.

Funding for the Martin Delaney Collaboratory comes primarily from the National Institute of Allergy and Infectious Diseases (NIAID), with a small contribution from the National Institute of Mental Health. Initially, the two institutes committed just $42.5 million to the collaborations and said that, at most, two would receive funding. NIAID Director Anthony Fauci explains that they scoured their budget to find what now totals $70 million for three groups because there was so much interest in cure research. "We asked our budget people if, without damaging other programs, can you scrape up a little bit here and a little bit there?" says Fauci. "At the end of the day, we came up with significant cash. We need to get people energized in this and show that we're putting the money up."

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Merck to Participate in New Research Efforts to Eradicate HIV

July 11, 2011 12:38 PM Eastern Daylight Time

WHITEHOUSE STATION, N.J.--(EON: Enhanced Online News)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that company researchers will participate in two new collaborative efforts led by the prominent academic institutions of the University of North Carolina (UNC) Chapel Hill and the University of California San Francisco (UCSF) to develop new approaches towards eradicating HIV, the virus that causes AIDS.

"Merck is honored and excited to participate in these important new undertakings."

As announced today by UNC, researchers from nine U.S. universities as well as Merck scientists will begin to study HIV latency and identify ways to purge persistent infection of the virus from the body. Separately, researchers at UCSF announced an international team of academic, governmental and Merck scientists will begin work on a five-year research effort to define HIV's reservoirs, better understand the reservoirs, and test potential treatments. The National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, is the primary funding organization for both of these research efforts. Merck will not receive any funding for its participation in either effort.

"Collaboration has been the hallmark of much of the progress made against HIV since the virus was first identified 30 years ago. Continued collaboration is absolutely essential to better understand HIV reservoirs and identify potential approaches to the daunting challenge of eradicating HIV," said Daria Hazuda, Ph.D., vice president, Merck Research Laboratories. "Merck is honored and excited to participate in these important new undertakings."

UNC research team

The research team led by the North Carolina Translational and Clinical Sciences (NC TraCS) Institute at UNC includes nineteen investigators from Case Western Reserve University; Johns Hopkins University; University of California, Davis; University of California, Los Angeles; University of California, San Diego; University of California, San Francisco; The Gladstone Institute; University of Minnesota, and the University of Utah. Merck is the team's sole pharmaceutical industry partner.

UCSF research team

The research team led by UCSF includes collaborators from Johns Hopkins University, the Vaccine and Gene Therapy Institute at Oregon Health and Science University (OHSU), the Oregon National Primate Research Center at OHSU, the University of Minnesota, Monash University, the American Foundation for AIDS Research (amfAR), the Blood Systems Research Institute, the Karolinska Institute, the University of Miami, and the University of California, Davis. Merck is the team's sole pharmaceutical industry partner.

Merck's history in HIV research and access

Merck has been engaged in the fight against HIV/AIDS for more than two decades. In 1988, Merck researchers were the first to demonstrate that inhibiting the protease enzyme would prevent replication of HIV; the following year, Merck scientists published the first crystal structure for HIV protease. Years later, Merck scientists were the first to demonstrate inhibition of HIV integrase in vitro and in vivo. Currently Merck scientists are actively pursuing HIV research against at least five distinct targets and have several HIV compounds in development. Since our first HIV medicines became available, Merck has worked to expand access to these medicines, including through partnerships with others.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com.

Forward-Looking Statement

This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; the risk of new and changing regulation and health policies in the United States and internationally and the exposure to litigation and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2010 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).

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Gladstone to receive $5.6 million in federal funds to seek a cure for AIDS

Participation in Martin Delaney Collaboratory increases hope of resolving HIV latency


SAN FRANCISCO, CA -- July 11, 2011 -- The Gladstone Institutes will receive funds totaling $5.6 million over five years as part of the first-ever major funding initiative focusing on HIV eradication. The funds will help three principal investigators at Gladstone, an independent biomedical-research organization, to explore the molecular basis for HIV latency where the virus that causes AIDS "hides" dormant within cells waiting for an opportunity to reemerge when therapy is withdrawn.

"A critical factor to finding a cure for AIDS is to solve the problem of HIV latency," said Warner Greene, MD, PhD who leads all virology and immunology research at Gladstone. "If we can inhibit latency, then a cure for HIV-infected patients could be within our reach."

AIDS has killed more than 25 million people around the world since first being identified some 30 years ago. In the United States alone, more than one million people live with HIV/AIDS at an annual cost of $34 billion. Patients require lifelong treatment for AIDS because the HIV virus persists in a dormant and drug-insensitive form. Better understanding this latency, and developing new ways to attack it, could finally make it possible to cure HIV-infected patients.

The funding to cure this latency is part of the Martin Delaney Collaboratory - a consortium among academia, government and private industry that the National Institutes of Health is funding and that Dr. Greene helped create. The National Institute of Mental Health also provided co-funding.

With these funds, Dr. Greene's laboratory will seek to identify previously unrecognized products in the cell that help maintain HIV latency - ultimately working to develop inhibitors against these cellular proteins. Dr. Greene's laboratory also will analyze the action and targets of various regulatory molecules known as microRNAs that are present in latently infected CD4 T cells. Eric Verdin, MD, will study the potential role of the cell's chromatin-remodeling machines in the establishment and maintenance of HIV latency; while Melanie Ott, PhD, will examine the role of histone methylation in HIV latency and the effects of small-molecule inhibitors that block the action of various methyl transferases.

"If we can successfully eradicate latency, we might be able to avoid drug therapy altogether," said Dr. Verdin, who is a senior investigator at Gladstone.

At the same time, Dr. Greene warned, any eventual cures or functional cures can't begin to end the global AIDS epidemic unless they can be effectively used in those places where the virus is most rampant - such as sub-Saharan Africa, where about two-thirds of all people afflicted with HIV/AIDS live.

"We must construct a therapy that is usable in both the developing and developed world," said Dr. Greene, who is also a professor of medicine, microbiology and immunology at the University of California, San Francisco (UCSF).

The $5.6 million that Gladstone is receiving is part of the $32 million that the National Institute of Allergy and Infectious Diseases (NIAID) has awarded over five years to the University of North Carolina at Chapel Hill. That money will be shared among 19 investigators, including those at Gladstone and at nine U.S. universities including UCSF, with which Gladstone is affiliated.

The UNC-led consortium will be one of three groups funded by NIAID under its Martin Delaney Collaboratory initiative. The UNC-led effort will undertake more than a dozen research projects to discover how the virus can remain dormant and virtually invisible, identify drugs and treatments capable of ridding the body of persistent infection and to evaluate these new strategies in relevant animal models followed by testing of the most promising candidates in humans.

The Collaboratory also includes an important industrial partner, Merck Research Laboratories of Whitehouse Station, N.J. Merck has a track record in the development of small-molecule drugs and other therapies that target viral reservoirs. While Merck Research Laboratories will not receive federal funds for their contribution to this research, they will provide core resources to the academic investigators.

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Martin Delaney was an internationally recognized AIDS activist who died in 2009. Delaney was a champion of the collaboratory concept to speed progress toward a cure for HIV infection through a public-private partnership involving government, academia and industry.

About the Gladstone Institutes

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and biomedical innovation, to prevent illness and cure patients suffering from cardiovascular disease, neurological diseases, or viral infections including HIV. Gladstone is affiliated with University of California, San Francisco.

 
 
 
 
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