Contact Information:

Media Contact

Deborah Robison

Twitter: SanfordBurnham

Kredyty mieszkaniowe Kredyty mieszkaniowe

Sprawdź aktualny ranking najlepszych kredytów mieszkaniowych w Polsce - atrakcyjne kredytowanie nieruchomości. - Press Release Distribution
RSS - Press News Release
Add Press Release

Researchers reawaken sleeping HIV in patient cells to eliminate the virus

An emerging class of drugs called Smac mimetics may lead to a safe and effective treatment to eradicate HIV

( LA JOLLA, Calif., September 9, 2015 - A consortium of investigators led by scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) have found that a new class of drugs may be used to purge pockets of dormant HIV from a patient's body, eliminating the virus once and for all. Since these agents are already being explored in clinical trials for treating cancer, the route to approval for treating HIV may be significantly shorter than usual.

Antiretroviral therapies have made it possible for people to live with HIV for decades. However, patients continue to harbor small and persistent reservoirs of cells that hide the virus. That is, HIV's genes live in the cells, but its genetic code is never read to make protein, and so the virus goes undetected by the immune system.

"If you take people off their antiretroviral therapies, some of these dormant cells reawaken to make more virus and re-establish disease," said lead author Lars Pache, Ph.D., a postdoctoral fellow in the lab of Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at SBP. "The key for a cure for HIV is to purge these cells that have dormant HIV."

Reactivating latent HIV-infected cells so that they can be killed off is called a shock-and-kill approach. The approach has remained elusive so far, because candidate drugs that reawaken the virus, known as latency reversing agents (LRAs), appear to lack sufficient potency, or alternatively, could trigger massive immune system activation, which itself could be deadly.

The new study, published September 9 in the journal Cell Host & Microbe, "uses a class of drug called Smac mimetics to tap into a molecular backdoor, a cell pathway that can be used as an intense alarm to wake up the virus, but doesn't appear to activate the immune system," Chanda said.

The study started with a broad search of genes within the host cells that help suppress the virus. They found that the absence of one gene in particular, BIRC2, boosted the activity of HIV, and Smac mimetics--already proven safe in early-stage clinical trials for cancer--work by inhibiting BIRC2 and related molecules.

"These experiments led us to develop a strategy of using Smac mimetics to reawaken dormant HIV so that it can be detected by the immune system and purged," explained Chanda.

Chanda's colleague at SBP, Nicholas Cosford, Ph.D., professor in the Cell Death and Survival Networks Program, had recently identified a potent BIRC2 inhibitor, SBI-0637142. "Although there are clinical- stage Smac mimetics available, they were not specifically developed for HIV-1 treatment. Our internal drug possesses about 10-100 times more potent LRA activity than the small molecules currently in clinical development, making it a promising next-generation candidate to tackle HIV latency," says Chanda.

Part of the reason that HIV's genes stay hidden in its host is that they cover themselves with tightly wound DNA. A class of drugs called histone deacetylase inhibitors, which unfurls the DNA, is used to treat a variety of conditions. Although most of these inhibitors haven't thus far worked well on their own to reactivate latent HIV, they might work well with Smac mimetics including SBI-0637142, Chanda's group reasoned.

The key question was whether they could reactivate the virus in cells from HIV-infected patients undergoing antiretroviral therapy. They combined SBI-0637142 with a histone deacetylase inhibitor (panobinostat) and saw signs that the virus had reawakened without triggering immune activation.

"We anticipated that we would see a synergy because the drugs work along parallel pathways. What we didn't expect was the level of activation and the efficacy with which we were able to reverse latency in patient samples," Chanda said.

They saw similar results in patient cells treated with a combination of LCL161--a Smac mimetic that is already in phase 1 and 2 trials for treating cancer--and panobinostat. "This is a one-two punch for HIV," said Chanda, adding that ultimately, a cocktail of drugs will likely be necessary to cure HIV.

The scientists hope to partner with a pharmaceutical company to develop these molecules for evaluation in clinical models of HIV latency and then move them into human testing if they meet the safety and efficacy criteria.


In addition to SBP, the study consortium included the University of Utah School of Medicine, The Salk Institute for Biological Studies, the Perelman School of Medicine at the University of Pennsylvania, the Icahn School of Medicine at Mount Sinai, the Paul-Ehrlich-Insitut, and the German Center for Infection Research.

This study was supported by NIH grants P01AI090935 to the HIV Immune Networks Team (; R01 DA033773, R01 AI087508 and the James B. Pendleton Charitable Trust

About Sanford Burnham Prebys Medical Discovery Institute Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit research organization that blends cutting-edge fundamental research with robust drug discovery to address unmet clinical needs in the areas of cancer, neuroscience, immunity, and metabolic disorders. The Institute invests in talent, technology, and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients. Recognized for its world-class NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs more than 1,100 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at The Institute can also be found on Facebook at and on Twitter @SBPdiscovery.


Battery-free smart camera nodes automatically determine their own pose and location

Scientists at Disney Research and the University of Washington (UW) have shown that a network of energy-harvesting sensor nodes equipped with onboard cameras can automatically determine each camera's pose and location using optical cues. This capability could help to enable networks of hundreds or thousands of sensors that could operate without batteries or external power and require minimal maintenance. Such networks could be part of the Internet of Things (IoT) in which objects can communicate and share information to create smart environments. Previous work at UW ...

Ebola virus disease in Liberia

A newly published research study by U.S. Forest Service researchers demonstrates that the social vulnerability indices used in climate change and natural hazards research can also be used in other contexts such as disease outbreaks. Authors of the article include Forest Service Southern Research Station (SRS) researchers John Stanturf, Scott Goodrick, Mel Warren, and Christie Stegall, and Susan Charnley from the Forest Service Pacific Northwest Research Station. Published in the online journal PLOS ONE, the study illustrates how census and household survey data, when ...

Study reveals need for better understanding of water use

WEST LAFAYETTE, Ind. -- A new study reveals a pressing need to better understand water use in America's rivers, with implications for drought-stricken regions of the country. Findings from the study showed that virtually all of the water entering the Wabash River in Indiana during summer months is withdrawn and then returned to the waterway. "In a nutshell, in the summertime we generally use what is equivalent to the entire volume of the Wabash River so that by the time the river reaches the confluence of the Ohio River, the water in the Wabash on average has been through ...

This week from AGU: Mercury's spin, New Zealand fault, early-career scientists and research

GeoSpace Mercury's movements give scientists peek inside the planet The first measurements of Mercury's movements from a spacecraft orbiting the planet reveal new insights about the makeup of the solar system's innermost world and its interactions with other planetary bodies, found a new study recently accepted in Geophysical Research Letters. New research calls for rethinking of New Zealand's Alpine Fault The major fault line of New Zealand's Alpine Fault, which runs almost the entire length of the South Island, has been assumed to be a near vertical crack. However, ...

High rate of Texas bugs carrying Chagas disease

High rate of Texas bugs carrying Chagas disease
A deadly parasite that causes Chagas disease is widespread in a common Texas insect, according to a new study by University of Texas at El Paso (UTEP) researchers. The finding suggests that the risk of Texans contracting the disease may be higher than previously thought. The parasite Trypanosoma cruzi (T. cruzi), which causes Chagas disease can be transmitted to humans by blood-sucking insects known as "assassin bugs" or "kissing bugs." Unlike mosquitoes that transmit malaria through the bite, kissing bugs drop feces on the subject while filling up with blood. The feces, ...

Association of low resting heart rate in men and increased violent criminality

A low resting heart rate in late adolescence was associated with increased risk for violent criminality in men later in life, according to an article published online by JAMA Psychiatry. Low resting heart rate is related to antisocial behavior in children and adolescents. Low resting heart rate (RHR) has been viewed either as an indicator of a chronically low level of psychological arousal, which may lead some people to seek stimulating experiences, or as a marker of weakened responses to aversive and stressful stimuli, which can lead to fearless behavior and risk taking. ...

Major complications, delirium associated with adverse events after elective surgery in older adults

Among patients 70 years or older who underwent elective surgery, major complications contributed significantly to a prolonged length of hospital stay while delirium contributed significantly to several adverse outcomes, including length of stay and hospital readmission, according to a study published online by JAMA Surgery. Major postoperative complications and delirium contribute independently to adverse outcomes and high resource use in patients who undergo major surgery; however, their interrelationship has not been well examined. Understanding the risks of adverse ...

Low rate secondary surgeries for removal, revision of vaginal mesh slings for stress urinary incontinence

A follow-up of nearly 60,000 women who received a synthetic vaginal mesh sling for the treatment of stress urinary incontinence finds the risk is low for needing a second surgery for mesh removal or revision (about 1 in 30 women ten years after surgery), according to a study published online by JAMA Surgery. Female stress urinary incontinence (SUI) is a common condition that is often treated with surgery when conservative management options are unsuccessful. An estimated 1 in 7 women will undergo surgery for SUI during their lifetime. Synthetic mesh slings are the most ...

Postoperative delirium results in poor outcomes in older adults

BOSTON -- Researchers from the Aging Brain Center at the Institute for Aging Research (IFAR) at Hebrew SeniorLife confirm that delirium is a significant and independent contributing factor to poor postsurgical outcomes in older adults. Findings published in JAMA Surgery suggest that the combination of major postoperative complications and delirium demonstrate a strong combined effect on adverse outcomes in older adults undergoing major surgery. Of all inpatient operations in the U.S. in 2007, 36% were performed on patients 65 years of age or older, and that number is ...

How the 'heat' compound from chili peppers could help kill cancer cells

Capsaicin, the compound responsible for chilis' heat, is used in creams sold to relieve pain, and recent research shows that in high doses, it kills prostate cancer cells. Now researchers are finding clues that help explain how the substance works. Their conclusions suggest that one day it could come in a new, therapeutic form. Their study appears in ACS' The Journal of Physical Chemistry B. About 10 years ago, researchers reported that capsaicin can kill prostate cancer cells in mice while leaving healthy cells unharmed. But translating that dose to humans would require ...


How your brain decides blame and punishment -- and how it can be changed

Uniquely human brain region enables punishment decisions

Pinpointing punishment

Chapman University publishes research on attractiveness and mating

E-cigarettes: Special issue from Nicotine & Tobacco Research

Placental problems in early pregnancy associated with 5-fold increased risk of OB & fetal disorders

UT study: Invasive brood parasites a threat to native bird species

Criminals acquire guns through social connections

Restoring ocean health

Report: Cancer remains leading cause of death in US Hispanics

Twin study suggests genetic factors contribute to insomnia in adults

To be fragrant or not: Why do some male hairstreak butterflies lack scent organs?

International team discovers natural defense against HIV

Bolivian biodiversity observatory takes its first steps

Choice of college major influences lifetime earnings more than simply getting a degree

Dominant strain of drug-resistant MRSA decreases in hospitals, but persists in community

Synthetic biology needs robust safety mechanisms before real world application

US defense agencies increase investment in federal synthetic biology research

Robots help to map England's only deep-water Marine Conservation Zone

Mayo researchers identify protein -- may predict who will respond to PD-1 immunotherapy for melanoma

How much water do US fracking operations really use?

New approach to mammograms could improve reliability

The influence of citizen science grows despite some resistance

Unlocking secrets of how fossils form

What happens on the molecular level when smog gets into the lungs?

Using ultrasound to clean medical instruments

Platinum and iron oxide working together get the job done

Tiny silica particles could be used to repair damaged teeth, research shows

A quantum lab for everyone

No way? Charity's logo may influence perception of food in package

[] Researchers reawaken sleeping HIV in patient cells to eliminate the virus
An emerging class of drugs called Smac mimetics may lead to a safe and effective treatment to eradicate HIV is a service of DragonFly Company. All Rights Reserved.
Issuers of news releases are solely responsible for the accuracy of their content.