US – Breaking science “silos” to find a HIV/AIDS vaccine

Created on 22 October 2012 Category: North America HIV News
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A chemical engineer, a polymer physicist and a chemist gather for coffee – and not much happens. “We could have all the greatest ideas in the world to discuss over coffee, but without funding, it is not possible do to more than napkin sketches,” said Darrell Irvine, a material scientist at the US-based Massachusetts Institute of Technology (MIT) who, along with dozens of scientists, have received funding to break down silos of scientific disciplines to create an AIDS vaccine.

Irvine is trying to deliver cancer drugs in a microscopic capsule that can target – and kill – viruses, including HIV.

Finding a safe, effective AIDS vaccine has, thus far, proved elusive even after some US$8 billion invested from 2001-2011 into vaccine research and development. Scientists point to HIV’s Houdini-like ability to escape immune system attack, and less-than-strategic use of funds over the past decade, as reasons for the continued hunt.

What vaccinologists can learn from stock traders - Photo: Flickr/Mike Baird

 

The most promising vaccine candidate so far, known as RV144, was shown to be 31 percent effective in Thailand, according to findings reported in 2009.

Follow-up testing with thousands of men who have sex with men in Thailand, and heterosexuals who are at high risk of getting HIV in South Africa, is being planned to see how to boost this vaccine combination’s efficacy, as well as adapt it to different HIV strains. Even under the best case scenario, it would be another decade before a vaccine will be licensed, according to Nina Russell, a senior programme officer with The Bill & Melinda Gates Foundation, taking into account how long it takes to plan and carry out a clinical trial, analyse results and gain licensure.

Back at the lab, convincing scientists to participate in the hunt for a vaccine is not easy, said Bruce Walker, the director of Ragon Institute, a collaboration founded in 2009 between medical and academic institutions in Massachusetts with private funding to speed up HIV vaccine development.

“I believe that many scientists would be delighted to apply their talents to a problem as huge as HIV, but see no clear path to doing so.”

When Walker approached Arup Chakraborty in 2008, a chemical engineer at MIT who has analysed scientific information using “statistical mechanics”, to work on HIV research, Chakraborty resisted. “I did not see what I could bring to a field that is already crowded. It is hard to stand out in a field where so many others are working,” he said. But after Walker took him to visit patients hospitalized with AIDS in South Africa, that changed. “I had never imagined such devastation,” said the scientist after his first encounters with people infected with HIV.

He and collaborators received one of Ragon’s “innovation awards”, $115,000 per year for up to two years, which allowed him to apply the same technology that helps investors pick stocks (random matrix theory) to study patient reactions to vaccines.

 

Cross-disciplinary research

In 2005 a coalition of research groups representing some 250,000 scientists in the US formed a “Coalition for the Bridging Sciences” to seek more US government funding for research that crossed over into more than one area of science. In its position paper it noted “computational biologists receive funding to model biological systems, but they generally do not receive support to solve the deeper problems.”

Such cross-over work and funding is still relatively scarce, said Chakraborty. “All our [US] universities are organized according to boundaries. It’s changing, but we are not there yet.”

Funding for cross-disciplinary research is still limited, said Ellen Weiss from the US non-profit Biophysical Society, which spearheaded the bridging science initiative. “Since 2005, US funding agencies have indicated an interest in making sure cross-disciplinary research does not fall between the cracks, but funding is still tight.”

In addition to the US National Institutes of Health and the National Science Foundation, which since 2010 have supported cross-disciplinary science research, the Gates Foundation committed $100 million in 2007 to encourage scientists to “expand the pipeline of their ideas”.

More than 500 researchers in about 40 countries have received $100,000 “Grand Challenger Exploration” grants, of whom 20 have received additional monies of up to $2 million.

 

“Chips” that hold cell samples for analysis

While scientists still largely work in the “silos” of their disciplines, said Irvine, there are more cases where technology developed for one purpose is being applied to biology.

Chris Love, an MIT chemist and Ragon funding recipient, is using technology behind semi-conductor chips (used in computers) to develop “chips” that hold cell samples for analysis. “Think of it like an ice cube tray where we can put cells from the immune system and then ask questions about… how they interact, how they respond to vaccines and drugs,” he said, holding out what appeared to be, simply, a glass slide.

“[As a chemist], you are used to solving problems where you have to build a new molecule. Here we have a problem where a lot of things have been tried, but there is no solution yet. As an engineer you look at it and you say, `I might be able to contribute something to this,’” he added.

Galit Alter, a professor of medicine at Harvard University, said there is a new generation of integration between the sciences, which has become a necessity when “silo” approaches have come up short on a vaccine. “With new tools, we are able to ask new questions,” said Alter.

The US-based International AIDS Vaccine Initiative (IAVI) calculates that an AIDS vaccine can prevent up to 10.7 million new HIV infections, saving up to $95 billion in treatment costs globally between 2020 and 2030, depending on the characteristics of the vaccine and its reach. IAVI’s modelling tool looked at scenarios for different regions of the world.

Based on the latest figures available from the Joint UN Programme on HIV/AIDS (UNAIDS), some 1.7 million people died from AIDS-related causes in 2011, while 34.2 million lived with HIV that year.

Author: Plus News
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Can diabetes medicines help prevent HIV-related nerve damage?

Created on 10 October 2012 Category: North America HIV News

People with HIV infection can develop damaged nerves in the hands, feet and legs. This condition is called peripheral neuropathy (PN). As a result of PN, people can develop very painful sensations in their limbs, such as burning or stabbing pains. They can also lose their ability to feel hot or cold in the affected limb. Sometimes, depending on the severity of nerve damage, they may even feel numbness. Neurologic testing can reveal reflexes that have degraded. Having symptoms of PN can impair quality of life.

PN can occur in people with HIV infection because the mitochondria (energy-producing parts) of cells become damaged. When mitochondria do not produce enough energy, nerve cells can malfunction or even die.

Some studies have found factors that may increase the risk for developing peripheral neuropathy, such as the following:

  • having a low CD4+ cell count
  • being older
  • being taller
  • excessive production of harmful substances by HIV-infected cells
  • exposure to so-called “d” drugs – older anti-HIV drugs that are no longer routinely recommended for first-line therapy in Canada or other high-income countries, such as ddI (didanosine, Videx), d4T (stavudine, Zerit) and ddC (zalcitabine, Hivid)
  • co-infection with CMV (cytomegalovirus)
  • excessive intake of vitamin B6 (pyridoxine)
  • deficiency of B-complex vitamins
  • excessive intake of alcohol
  • having diabetes
  • excessive exposure to drugs with the potential to cause nerve damage, including the antibiotics isoniazid and metronidazole (Flagyl); the anticancer drugs vincristine, etoposide, paclitaxel, docetaxel and cisplatinum

A research team in the U.S. recently reviewed health-related information collected from 1,592 HIV-positive people (80% men, 20% women) in an attempt to find associations between various factors and the future risk for developing symptoms of PN in people who had symptom-free PN. Participants were monitored for about five years and underwent neurologic and other assessments.

The researchers found that exposure to what they called “neurotoxic ART” (combinations that included “d” drugs) was associated with a twofold increased risk for developing symptoms of peripheral neuropathy.

However, what surprised the researchers was that participants who used medicines other than insulin (such as metformin (Glucophage)) to help control their blood sugar were less likely to develop symptoms of PN.

Due to the observational nature of the present study’s design, its conclusions are not definitive. However, they are suggestive of a protective effect of diabetes medicines on nerves. The researchers are not certain how or why this occurred.

Muscle and fat cells are dependent on insulin to help pull sugar from the blood into them so that that their mitochondria can use sugar as a source of energy. Canadian researchers have found that while nerve cells are not dependent on insulin for helping to transport sugar from the blood into nerve cells, these cells are sensitive to its effects. That is, insulin might have other effects on nerves, perhaps helping them grow and survive. If nerve cells in the periphery (outside of the brain and spinal cord) lose their sensitivity to insulin, they can malfunction and degenerate. Many diabetes medicines work by making cells more sensitive to the effects of insulin and that may be one possible way that these drugs could help prevent the worsening of peripheral neuropathy.

The findings from the U.S. study about the potentially beneficial effects of insulin-sensitizing agents such as metformin in HIV-positive people at risk for symptoms of PN need to be confirmed in a study of a more robust design. If they are confirmed, clinical trials of insulin-sensitizing agents commonly used in the management of type 2 diabetes may be the next step. Such research may, in part, explain the beneficial effect of the antioxidant alpha-lipoic acid, which has been tested in clinical trials of HIV-negative people with peripheral neuropathy and to help improve insulin sensitivity.