Too good to be true? You might think this is impossible.
Now, in a development that could transform how viral infections are treated, a team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.
It works against 15 viruses tested so far.
In a paper published July 27 in the journal PLoS One, the researchers tested their drug against 15 viruses, and found it was effective against all of them — including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.
When they infect a cell some (all?) viruses cause a type of RNA to be produced that makes the infected cell distinct from uninfected cells. Hence the ability to target and just kill the infected cells.
The drug works by targeting a type of RNA produced only in cells that have been infected by viruses. “In theory, it should work against all viruses,” says Todd Rider, a senior staff scientist in Lincoln Laboratory’s Chemical, Biological, and Nanoscale Technologies Group who invented the new technology.
Because the technology is so broad-spectrum, it could potentially also be used to combat outbreaks of new viruses, such as the 2003 SARS (severe acute respiratory syndrome) outbreak, Rider says.
Imagine this works and has few side effects. If one could get hundreds of millions of people to all take the drug at the same time viruses could be wiped out over a large area. The problem of course would be with travelers. Trying to get everyone on the planet to take a drug at the same time seems impractical. Even getting everyone in a country to take the drug simultaneously seems impossible.
A drug of this sort might work well for a submarine crew. At the start of a voyage into isolation everyone could take the drug and wipe out all viruses in the crew.
Opening a new front in the war against flu, researchers at the University of Wisconsin-Madison have reported the discovery of a novel compound that confers broad protection against influenza viruses, including deadly avian influenza.
The new work, reported online this week (Oct. 4, 2006) in the Journal of Virology, describes the discovery of a peptide - a small protein molecule - that effectively blocks the influenza virus from attaching to and entering the cells of its host, thwarting its ability to replicate and infect more cells.
The new finding is important because it could make available a class of new antiviral drugs to prevent and treat influenza at a time when fear of a global pandemic is heightened and available antiviral drugs are losing their potency.
"This gives us another tool," says Stacey Schultz-Cherry, a UW-Madison professor of medical microbiology and immunology and the senior author of the new report. "We're quickly losing our antivirals."
In event of a killer flu strain pandemic rapid shift of this peptide into production and distribution could save millions of lives.
The new drug, which was tested on cells in culture and in mice, conferred complete protection against infection and was highly effective in treating animals in the early stages of infection. Untreated infected animals typically died within a week. All of the infected animals treated with small doses of the drug at the onset of symptoms survived."Pretreatment with (the peptide) provided 100 percent protection against numerous subtypes (of flu), including the highly pathogenic H5N1 viruses," according to the Journal of Virology report.
The new drug, known as "entry blocker," is a fragment of a larger human protein whose role in biology is to help things pass through membranes such as those that encapsulate cells.
I am amazed at how effective this peptide is in animals. We need human trials.
The peptide blocks influenza viruses at a much earlier stage than existing anti-viral drugs such as Tamiflu.
"It attacks a completely different part of the virus life cycle," explains Curtis R. Brandt, a co-author of the study and a UW-Madison professor of medical microbiology and immunology and of ophthalmology and visual sciences. "The virus can't even get into the cell. The peptide is blocking the very earliest step in infection."
An influenza pandemic could kill tens or even hundreds of millions of people if it happened in the short term. But in the medium to long term I think influenza will become a completely defeated disease. 10 years from now at least in industrialized countries the risk of a killer pandemic seems small. We'll have biotechnologies for rapidly scaling up vaccine production. We'll also have far better anti-virals such as this peptide discovered at the University of Wisconsin. I expect we'll also have very good drugs for controlling the inflammation response so that an excessive immune and inflammation response won't fatally damage the bodies of infected people.
Altering the makeup of bugs in the gut could be a way of tackling insulin resistance and related problems such as non alcoholic fatty liver disease, according to new research published this week.
The study also has implications for the treatment of associated conditions such as type 2 diabetes, obesity and heart disease.
The research shows that the type of microbes found in the guts of mice with a certain genetic makeup causes them to be pre-disposed to insulin resistance and non-alcoholic fatty liver disease (NAFLD). On a high fat diet, these microbes transform the nutrient choline, found in food and essential for metabolising fat, into methylamines.
Scientists believe that these methylamines, which can only be produced by the microbes in the gut, lead to insulin resistance. In addition, because choline is needed to transport fat out of the liver, altering choline metabolism leads to fat accumulating in the liver and NAFLD.
This is good news. Why? Bacteria can be defeated. Any time I read about how some disease is caused by chronic infection it makes me more optimistic. We can develop drugs and vaccines that'll stop pathogens. Better that chronic diseases of old age be caused by pathogens than by the body simply wearing out. The pathogens are easier to stop than the wearing out of cells.
Here is part of the abstract from the PNAS paper for this report. Bacteria reduce choline availability while also increasing exposure to harmful methylamines.
Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 129S6 mouse to impaired glucose homeostasis and NAFLD is associated with disruptions of choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine and high urinary excretion of methylamines (dimethylamine, trimethylamine, and trimethylamine-N-oxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiota in strain 129S6 on a high-fat diet reduces the bioavailability of choline and mimics the effect of choline-deficient diets, causing NAFLD. These data also indicate that gut microbiota may play an active role in the development of insulin resistance.
The practical question: Can we use this information now? We need answers to some basic questions: Which human stomach bacteria convert choline to methylamines? Do they all do this? Are antibiotics or the consumption of competing bacteria the best way to shift the balance of bacteria in the stomach away from bacteria that convert choline to methylamine?
Anyone know the answers to these questions?
Researchers in the European Molecular Biology Laboratory located in Heidelberg, Germany have discovered mosquito proteins that determine how well the malaria parasite falciparum plasmodium reproduces in mosquitoes.
EMBL scientists have identified four mosquito proteins that affect the ability of the malaria parasite (Plasmodium) to survive and develop in the malaria-carrier mosquito (Anopheles). This breakthrough, featured in recent issues of Cell (March 5, 2004) and Science (March 26, 2004), could be used to block the transmission of malaria from mosquitoes to humans.
"Many researchers focus on the direct effects of Plasmodium on the human body but the mosquito is an equally important battleground in fighting the disease," notes Prof. Fotis C. Kafatos, EMBL's Director-General and leader of the group focusing on malaria research. "We now see a way to potentially stop the parasite in its tracks."
The malaria parasite has to be able to reproduce in the mosquito in order to be able to infect humans.
When a blood-feeding Anopheles mosquito bites an infected organism, the insect feeds on its blood - taking in the malaria-causing Plasmodium. After three weeks of developing within the mosquito, the Plasmodium moves from the insect gut into the salivary glands and is ready for transmission: at the next bloodmeal it will be injected into the bloodstream along with the mosquito's saliva, initiating a new infection cycle.
But one fact that had continued to puzzle malaria researchers is why within one mosquito species, some mosquitoes transmit malaria (termed "susceptible"), whereas others do not ("refractory"). It was suspected that protein factors of the mosquito's immune system might be responsible for this difference. EMBL scientists have now shown this to be the case - with a new twist.
Two of these mosquito proteins, TEP1 and LRIM1, were shown to be true defenders of the mosquito - killing the parasite in the insect's gut.
"The TEP1 and LRIM1 studies proved that the mosquito's immune system has the ability to defend itself against malaria. By enhancing these natural defenders, we may be able to block the parasite-mosquito cycle," says EMBL PhD student Stephanie Blandin, who worked on the TEP1 studies with CNRS researcher (and EMBL alumna) Elena Levashina and collaborators from the University of Leiden (The Netherlands).
"Our studies on TEP1 represent an important step because they show that TEP1 specifically locks onto the Plasmodium and it is this binding that mediates the killing of the parasite," notes Levashina. "Different forms of this protein are present in susceptible and refractory mosquitoes, potentially accounting for the fact that refractory mosquitoes do not sustain parasite development."
In the Kafatos Group, a collaboration between postdoctoral fellow Mike Osta and Staff Scientist George Christophides revealed a new twist: in addition to the mosquito defender protein LRIM1, they discovered two proteins, CTL4 and CTLMA2, which have an opposite effect, actually protecting the parasite as it develops in the mosquito gut. If these proteins were eliminated, the parasites died.
One way to use this new information would be to develop chemicals aimed at these proteins to strip away protection that these proteins provide to falciparum plasmodium. The chemicals would be used in a fashion analogous to pesticides but with the aim of allowing mosquito immune systems to kill the malaria parasite rather than killing the mosquitoes.
"It is now clear that if we strip away protective proteins, the parasite becomes vulnerable to the mosquito's immune system," Christophides notes. "Developing novel chemicals to inhibit the ability of such proteins to protect the parasite is a promising avenue to decrease the prevalence of malaria."
Prof. Kafatos agrees. "These studies are the first to show the power of the mosquito's immune system and give us some very real options for fighting the disease in the insect before it even has a chance to be passed to a human," he explains. "There is no single 'magic bullet' for controlling this ancient scourge of humanity, but we want to exploit this new lead to contribute to the defeat of malaria."
When one gene, called CTL4, is inactivated, the mosquitoes destroy up to 97% of the parasites developing inside their bodies. When the other, called LRIM1, is removed, it has the opposite effect: the parasites multiply readily.
The more radical approach to stopping the malaria parasite would be to make genetically engineered mosquitoes that are highly resistant to falciparum plasmodium infection and release those mosquitoes into the wild to displace existing wildtype mosquitoes.
The discoveries have raised new possibilities for stopping mosquitoes from spreading the parasite. For example, genetically engineering mosquitoes with extra genes to attack the parasites, or lacking the genes that protect them, could help.
One objection raised to this approach is that it would be difficult to displace all wildtype mosquitoes. But repeated releases of genetically engineered mosquitoes could make a large dent in the population of wildtype and at the very least decrease the rate of human infection by malaria. Consider the number of lives at stake. Currently every year 300-500 million people are infected and 1.5-2.7 million people die from malaria. Malaria causes damage to livers, kidneys, and other parts of the body. Even the people who do not die and who are not permanently damaged still suffer and are far less able to work and provide for themselves and their families. Those numbers represent a great deal of human suffering.
This is an idea that could be applied to a number of other diseases by making analogous discoveries in other insects and bugs to find out how to make them resistant to pathogens that they pass on to humans. Genetic engineering of ticks, mosquitoes, and other bugs could protect humans against Lyme Disease, West Nile Virus, and other pathogens transmitted by various sorts of creatures. This idea could even be extended as far as genetically engineering chickens, pigs, and other organisms to be more resistant to influenza infection in order to reduce the risk of virulent influenza strains jumping from other species into humans.
Many of the usual suspects who are opposed to genetically modified food crops can be expected to oppose genetic engineering of mosquitoes and other bugs. But the potential number of lives saved could run into the millions and even the tens of millions over a longer period of time. One big advantage of genetic engineering is that it avoids the costs, potential human health risks, and potential environmental harm that would come from repeated application of chemicals in areas where malaria or some other disease is being spread by insects into the human population.