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Archive - 2011 - Story

November 11th

New Artemisinin-Based Combination Treatment Promising for Malaria

For some time now, artemisinin, derived from a Chinese herb, has been the most powerful treatment available against malaria. To avoid the malaria parasite becoming resistant, the World Health Organization (WHO) strongly recommends combining artemisinin with another anti-malarial drug. But there are different formulations and derivatives, in different combinations, and with dosing schemes. Scientists from the Institute of Tropical Medicine (ITM) carried out a head-to-head comparison of four combination therapies in seven African countries. One combination appeared particularly promising for regions where the risk of re-infection is high. Malaria is caused by several related parasites, of which Plasmodium falciparum is the worst. The parasites have a complicated life cycle, partly in mosquitoes. When an infected mosquito bites a human, parasites are injected with the mosquito saliva into the blood, travel to the liver, where they change form, then infect red blood cells, where they further reproduce. After a few days (depending on the parasite species), the red blood cells burst to release a huge number of new parasites. These bursts cause intense fever, anaemia, and renal problems. Each year, approximately 800,000 people die of malaria. In recent years, the burden of malaria has declined substantially in several sub-Saharan African countries, due to large scale indoor residual spraying of insecticides, massive distribution of insecticide-treated bed nets, and the introduction of artemisinin-based combination treatments, ACTs for short. To treat patients with malaria, the WHO advises each region to choose an ACT based on the local level of resistance to non-artemisinin medicine in the combination. But data on that resistance are scarce.

Cholera Vacccine Prequalified by WHO

Shanchol™, a new oral cholera vaccine developed through the International Vaccine Institute (IVI), an international organization established by the United Nations and based in Seoul, Korea, recently received prequalification from the World Health Organization (WHO). Developed for use in developing countries to protect against life-threatening cholera, Shanchol™ is ready to use in a single-dose vial and is administered orally, which facilitates its implementation in large-scale immunization programs. Shanchol™ is produced by Shantha Biotechnics – part of the Sanofi group - in India where the vaccine has been licensed and sold since 2009. "I am immensely pleased by the news that Shanchol™, a vaccine enabled by IVI, received WHO prequalification," said Dr. Christian Loucq, IVI's new Director General. "This stamp of approval shows that public-private partnerships - such as those among IVI, Vabiotech, Shantha, and Sanofi – are essential for successful vaccine development, particularly in developing vaccines against neglected diseases of the poor like cholera." Certification by WHO of Shanchol™ represents a major milestone as it indicates that the vaccine meets WHO standards of quality, safety, and efficacy, and allows the vaccine to be procured by UN agencies and other international organizations for use in countries around the world. It also accelerates international use of the vaccine because WHO prequalification eliminates the need for country-level market authorization in some countries, which can take years to obtain. WHO prequalification of Shanchol™ is the latest achievement in IVI's mission to develop and introduce innovative, safe, and effective vaccines to protect vulnerable populations in poor countries against deadly diseases including cholera.

November 10th

Mutations in Hereditary Parkinson’s Disease Disrupt System for Disposing of Damaged Mitochondria

Current thinking about Parkinson's disease is that it's a disorder of mitochondria, the energy-producing organelles inside cells, causing neurons in the brain's substantia nigra to die or become impaired. A study from Children's Hospital Boston now shows that genetic mutations causing a hereditary form of Parkinson's disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them. Findings appear in the November 11, 2011 issue of Cell. Mitochondrial movement is often a good thing, especially in neurons, which need to get mitochondria to cells' peripheries in order to fuel the axons and dendrites that send and receive signals. However, arresting this movement is equally important, says senior investigator Dr. Thomas Schwarz, of Children's F.M. Kirby Neurobiology Center, because it allows mitochondria to be quarantined and destroyed when they go bad. "Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too," Dr. Schwarz says. "It's the equivalent of an environmental disaster in the cell." Studying neurons from fruit flies, rats, and mice, as well as cultured human cells, Dr. Schwarz and colleagues provide the most detailed understanding to date of the effects of the gene mutations, which encode the mutated forms of the proteins Parkin and PINK1. They demonstrate how these proteins interact with proteins responsible for mitochondrial movement -- in particular Miro, which literally hitches a molecular motor onto the organelle. Normally, when mitochondria go bad, PINK1 tags Miro to be destroyed by Parkin and enzymes in the cell, the researchers showed. When Miro is destroyed, the motor detaches from the mitochondrion.

Potential New Target for Slowing Spread of Breast Cancer

A new potential target to slow breast cancer tumor progression and metastasis has been identified by a team of researchers led by Dr. Richard Kremer from the Research Institute of the McGill University Health Centre (RI-MUHC). Complications in breast cancer patients are commonly caused by the spread of the disease through metastasis to other parts of the body, most often to the bones and lungs. The new findings, published online on November 7, 2011 in the Journal of Clinical Investigation (JCI), suggest that a specific protein plays a key role in the progression of the disease outside of the initial tumor area. Researchers showed that this particular target, called parathyroid hormone-related protein (PTHrP), present at high levels in cancers, is involved in key stages of breast cancer initiation, progression, and metastatic spread in mice. "We are hoping for a significant effect on the prevention of breast cancer recurrence, growth, and development by using a strategy to decrease the production of that particular protein," says Dr. Richard Kremer, co-director of the Musculoskeletal Axis of the RI-MUHC and a professor in the Department of Medicine at McGill University. To better understand the role of PTHrP in cancer development, researchers eliminated the production of the hormone from mouse breast cells using a strategy called "conditional knockout" and then studied the progression of the tumor. "The results showed that without the presence of PTHrP in the breast, even before the tumor developed, a reduction of 80 to 90 per cent in the growth of the tumor was observed," explains Dr. Kremer. "The removal of this hormone in the breast and breast tumors blocks not only the growth of the tumors, but also its spread to different organs." In order to bring this strategy one step closer to the patient, Dr.

Protein Interactions and Queen Determination in Honey Bees

A honey bee becomes a royal queen or a common worker as a result of the food she receives as a larva. While it has been well established that royal jelly is the diet that makes bees queens, the molecular path from food to queen is still in dispute. However, scientists at Arizona State University, led by Adam Dolezal and Dr. Gro Amdam, together with colleagues at other institutions, have helped reconcile some of the conflicts about bee development and the role of insulin pathways and partner proteins. Their article "IRS and TOR nutrient-signaling pathways act via juvenile hormone to influence honey bee cast fate" has been published in the December 2011 issue of the Journal of Experimental Biology. Central to the dispute within the scientific community about "who would be queen" has been a ground-breaking study published in the journal Nature in 2011 by Japanese scientist Dr. Masaki Kamakura of the Biotechnology Research Center, Toyama Prefectural University. He found that a single protein in royal jelly, called royalactin, activated queen development in larval bees through interaction with an epidermal growth factor receptor (EGFR). Dr. Kamakura's work suggested that insulin signals do not play a role in queen development, despite previous studies suggesting otherwise, including work pioneered with the insulin receptor protein by Dr. Amdam's group. Undeterred by Dr. Kamakura's findings, Dolezal, a doctoral student, and Dr. Amdam, a Pew Biomedical Scholar and professor in ASU's School of Life Sciences, looked for ways to resolve the disparity between the research studies. Amdam's team's first step involved taking control of the insulin receptor's partner protein, IRS, which the insulin receptor relies upon for signaling.

November 9th

Scientists Investigate “Panhandle” Structure of Salmon Virus RNA

A research team at the National Institute of Standards and Technology (NIST) has provided the first look at a genetic structure that may play a critical role in the reproduction of the infectious salmon anemia virus (ISAV), more commonly known as the "fish flu." A scourge in fish farms with a mortality rate as high as 90 percent, ISAV was recently found in wild salmon in the Pacific Northwest for the first time, threatening an already dwindling population and the vast food web it supports. The new research was published online on October 12, 2011 in the Journal of Virology. While there is a vaccine for the virus, it must be administered by injection—a task that is both cumbersome and economically impractical for the aquaculture industry. A drug or vaccine that prevents the spread of the disease by interfering with the virus' ability to replicate its genetic code (contained in eight segments of RNA) would be far more practical for fish farmers and marine biologists to deliver. Dr. Robert Brinson, a NIST scientist working at the Hollings Marine Laboratory (HML) in Charleston, South Carolina, and NIST colleagues Drs. Andrea Szakal and John Marino working at the Institute for Bioscience and Biotechnology Research (IBBR) in Rockville, Maryland, knew from the scientific literature that the family of viruses that includes both the many types of influenza—the causes of yearly human flu outbreaks—and infectious salmon anemia, form "panhandle" structures in their genomic RNA. In human influenza, these panhandles are known to interact with proteins that begin the process of copying and replicating the virus.

Proof-of-Principle for RNAi Treatment of Genetic Bone Disease

Scientists at Penn’s Perelman School of Medicine Center for Research in FOP and Related Disorders have developed a new genetic approach to specifically block the damaged copy of the gene for a rare bone disease, while leaving the normal copy untouched. Lead author Dr. Josef Kaplan, postdoctoral fellow; and senior authors Dr. Eileen M. Shore and Dr. Frederick S. Kaplan, both from the Department of Orthopaedic Surgery, published this new proof-of-principle approach for treating the disease, called FOP, online on October 20, 2011 in Gene Therapy. FOP (fibrodysplasia ossificans progressive) is a rare genetic disorder of progressive extra bone formation for which there is presently no cure. It is caused by a mutation in the gene for ACVR1/ALK2, a bone morphogenetic protein (BMP) receptor that occurs in all classically affected individuals. Individuals who have FOP harbor one normal copy and one damaged copy of the ACVR1/ALK2 gene in each cell. The mutation increases the amount of BMP in cells to greater than normal levels, which initiates the transformation of muscles and cartilage into a disabling second skeleton of bone. Using a special type of RNA molecule engineered to specifically silence the damaged copy of the gene rather than the normal copy -- a process known as RNA interference, or RNAi -- the scientists restored the cellular function caused by the FOP mutation by ridding cells of the mutant ACVR1/ALK2 mRNA. Cells were essentially left with only normal copies of ACVR1/ALK2 mRNA, thus adjusting the protein’s activity to normal, similar to that of cells without the FOP mutation. The human cells used in the experiments were adult stem cells obtained directly from discarded baby teeth donated by FOP patients.

Lipid Blocks Influenza Infection

A natural lipid in the fluid lining the lungs inhibits influenza infections in both cell cultures and mouse models, according to researchers at National Jewish Health. These findings, combined with previous studies demonstrating effectiveness against respiratory syncytial virus, suggest that the lipid molecule, known as POPG, may have broad antiviral activity. “Supplemental POPG could be an important, inexpensive, and novel approach for the prevention and treatment of influenza and other respiratory virus infections,” said Dr. Dennis Voelker, Professor of Medicine, and senior author of the report, published online on November 3, 2011 in the American Journal of Respiratory Cell and Molecular Biology. Influenza infects millions of people across the globe, killing 500,000 each year. Vaccines are highly effective, but must be reformulated each year to counter new viral strains. Two classes of drug are currently available to treat established influenza infections, although widespread resistance has developed against one class and is developing against the other. Several proteins that inhibit viral activity have been identified in the fluid lining the lungs. Until recently, however, the antiviral role of POPG (palmitoyl-oleoyl-phosphatidylglycerol) has been unknown. Previous research by Dr. Voelker, Dr. Mari Numata, and their colleagues demonstrated that POPG reduces inflammation in the lung and prevents infection by respiratory syncytial virus. In the most recent study, the researchers looked at the ability of POPG to inhibit infection by two strains of influenza, H1N1-PR8 and H3N2. They found that POPG suppressed inflammatory responses, viral propagation, and cell death normally associated with influenza infection.

Advance in Understanding the Genetics of High Blood Pressure

A researcher from the UK’s University of Leicester's Department of Cardiovascular Sciences has been involved in a ground-breaking study into the causes of high blood pressure. The study, published online on October 31, 2011 in the academic journal Hypertension, analyzed genetic material in human kidneys in a search for genes that might contribute to high blood pressure. The findings open up new avenues for future investigation into the causes of high blood pressure in humans. The study identified key genes, messenger RNAs, and micro RNAs present in the kidneys that may contribute to human hypertension. It also uncovered two microRNAs that contribute to the regulation of renin – a hormone long thought to play to part in controlling blood pressure. Although scientists have long known that the kidneys play a role in regulating blood pressure, this is the first time that key genes involved in the process have been identified through a large, comprehensive gene expression analysis of the human kidneys. It is also the first time that researchers have identified miRNAs that control the expression of the hormone renin. The scientists studied tissue samples from the kidneys of 15 male hypertensive patients and 7 male patients with normal blood pressure, and compared their messenger RNA (mRNA) and microRNA (miRNA). Messenger RNA (mRNA) is a single-stranded molecule that helps in the production of protein from DNA. Genetic information is copied from DNA to mRNA strands, which provide a template from which the cell can make new proteins. MicroRNA (miRNA) is a very small molecule that helps regulate the process of converting mRNA into proteins. The study was co-authored by the University of Leicester's Dr.

Polio Still a Threat to Public Health

Health professionals and researchers across the globe believe they are on the verge of eradicating polio, a devastating virus which can lead to paralysis and death. Despite successful eradication in most countries, there are still four countries where the virus is considered endemic -- and many more in which the virus still lurks. Dr. Lester Shulman of Tel Aviv University's Sackler Faculty of Medicine and the Israeli Ministry of Health has spent years tracking isolated cases of live poliovirus infections, often discovered in countries that are supposedly polio-free. When the live-virus version of the vaccine, called Oral Polio Vaccine (OPV) evolves, he says, it can act like wild poliovirus and continue the threat of contagion. Medical professionals widely believe that after the wild virus is eradicated, resources dedicated to polio immunization can be redirected. But this isn't so, Dr. Shulman says. He recommends that public health agencies take a three-pronged approach: vaccination policies to maintain "herd immunity" (a 95 percent immunization rate for polio) should be maintained to prevent the spread of wild and evolved vaccine strains of the virus; environmental surveillance of sewage systems should continue; and a switch to Inactivated Polio Vaccine (IPV) instead of OPV should be implemented. Dr. Shulman's research was recently published in PLoS ONE. He has also been invited as an informal expert to the World Health Organization's annual meeting on polio this fall. While the eradication of polio is seemingly within reach, this is not the time to relax, Dr. Shulman warns. Most countries only investigate the possibility of poliovirus outbreaks when paralytic cases appear in the human population. But this doesn't take into account a potential problem posed by the live virus vaccine.