DNA Packaging Discovery Reveals Principles by Which CRC Mutations May Cause Cancer (Eagle Group- Nov19, 2012)

The discovery, by Bradley R. Cairns, PhD, Senior Director of Basic Science at HCI and a professor in the Department of Oncological Sciences, is reported in this week's online issue of the journal Nature.

Cairns's research focuses on chromatin remodeling complexes (CRCs), which are cellular protein complexes that behave like motors, expanding or compacting different portions of DNA to either express or silence genes, respectively. Before, scientists thought that the motor within CRCs waits at rest until it receives instructions. Cairns and co-author Cedric R. Clapier show that the motor within a key CRC responsible for gene packaging and assembly is intrinsically turned on, and instead requires specific instructions to turn it off.

"Many articles in the research literature show that CRCs are mutated in cancer cells. They are intimately involved in regulating gene expression -- responsible for correctly packaging genes that control growth proliferation and for unpackaging tumor suppressors," said Cairns. "This research reveals principles by which CRC mutations could cause cancer."

Chromosomes are made of long DNA strands compressed around nodes of protein called nucleosomes; when DNA is compressed, the genes in that area are turned off. Some CRCs, called disassembly CRCs, act as motors that unwind sections of DNA chains, making genes active for a given cell process. Another type, called assembly CRCs, rewinds the DNA chain, recompressing it when the process is complete. The unwind-rewind cycle is repeated continuously throughout a cell's life.

In this study, Cairns and Clapier focused on assembly CRCs. "Before this research, we thought that the motor was off unless a protein coming from another part of the cell turned it on," said Cairns. "Researchers have been searching for the switch by looking at the CRC motor to see what binds to it.

"As it turns out, we discovered that the CRC motor already carries on its flank a 'switch' that inhibits its action until a marker sequence, located on the nucleosome, is encountered. The marker flips the inhibitor switch and allows the CRC to crank the DNA chain back around the nucleosome, promoting gene packaging and silencing" Cairns said. "Our results change where future researchers should be looking to understand how CRCs are regulated -- not at the CRC motor itself, but at the 'switches' that flank the motor."

The study also describes a measuring function on the CRC that checks for the correct distance between one nucleosome and the next, telling the motor to switch off at the proper time, a function needed for gene silencing.

Cairns's lab will now examine this same switching concept in disassembly remodelers. "There are additional remodeler families with alternative functions, like DNA repair," said Cairns. "We think this concept will apply to them as well."

This research was supported by funding from the National Institutes of Health (GM60415 and CA042014) and from the Howard Hughes Medical Institute.

Journal Reference:

1.      Cedric R. Clapier, Bradley R. Cairns. Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 2012; DOI:10.1038/nature11625

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The above story is reprinted from materials provided by University of Utah Health Sciences.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Reconsidering Cancer's Bad Guy (Eagle Group- Nov 19, 2012)

Researchers at the University of Copenhagen have found that a protein, known for causing cancer cells to spread around the body, is also one of the molecules that trigger repair processes in the brain.

How to repair brain injuries is a fundamental question facing brain researchers. Scientists have been familiar with the protein S100A4 for some time as a factor in metastasis, or how cancer spreads. However it's the first time the protein has been shown to play a role in brain protection and repair.

"This protein is not normally in the brain, only when there's trauma or degeneration. When we deleted the protein in mice we discovered that their brains were less protected and able to resist injury. We also discovered that S100A4 works by activating signalling pathways inside neurons," says Postdoc Oksana Dmytriyeva, who worked on the research in a team at the Protein Laboratory in the Department of Neuroscience and Pharmacology at the University of Copenhagen.

The villain turns out to be the hero

This research stands on the shoulders of many years of work on S100A4 in its deadlier role in cancer progression. The discovery represents a significant development for the new Neuro-Oncology Group that moved to the University of Copenhagen's Protein Laboratory Group from the Danish Cancer Society in October.

"We were surprised to find this protein in this role, as we thought it was purely a cancer protein. We are very excited about it and we're looking forward to continuing our research in a practical direction. We hope that the findings will eventually benefit people who need treatment for neurodegenerative disorders like Alzheimer's disease, although obviously we have a long way to go before we get to that point," says Oksana Dmytriyeva.

The scientific paper The metastasis-promoting S100A4 protein confers neuroprotection in brain injury can be found online in the journal Nature Communications.

Journal Reference:

1.      Oksana Dmytriyeva, Stanislava Pankratova, Sylwia Owczarek, Katrin Sonn, Vladislav Soroka, Christina M. Ridley, Alexander Marsolais, Marcos Lopez-Hoyos, Noona Ambartsumian, Eugene Lukanidin, Elisabeth Bock, Vladimir Berezin, Darya Kiryushko. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury.Nature Communications, 2012; 3: 1197 DOI:10.1038/ncomms2202

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The above story is reprinted from materials provided by University of Copenhagen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
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Breakthrough Nanoparticle Halts Multiple Sclerosis in Mice, Offers Hope for Other Immune-Related Diseases (Eagle Group-Nov 19, 2012)

The new nanotechnology also can be applied to a variety of immune-mediated diseases including Type 1 diabetes, food allergies and airway allergies such as asthma.

In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can't be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.

The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.

"This is a highly significant breakthrough in translational immunotherapy," said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. "The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered."

"The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin," Miller added. "Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact."

The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.

"This is a major breakthrough in nanotechnology, showing you can use it to regulate the immune system," said Shea, also a corresponding author. The paper will be published Nov. 18 in the journal Nature Biotechnology.

Miller and Shea are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. In addition, Shea is a member of the Institute for BioNanotechnology in Medicine and the Chemistry of Life Processes Institute.

Clinical Trial for Ms Tests Same Approach -- With Key Difference

The study's method is the same approach now being tested in multiple sclerosis patients in a phase I/II clinical trial -- with one key difference. The trial uses a patient's own white blood cells -- a costly and labor intensive procedure -- to deliver the antigen. The purpose of the new study was to see if nanoparticles could be as effective as the white blood cells as delivery vehicles. They were.

The Big Nanoparticle Advantage for Immunotherapy

Nanoparticles have many advantages; they can be readily produced in a laboratory and standardized for manufacturing. They would make the potential therapy cheaper and more accessible to a general population. In addition, these nanoparticles are made of a polymer called Poly(lactide-co-glycolide) (PLG), which consists of lactic acid and glycolic acid, both natural metabolites in the human body. PLG is most commonly used for biodegradable sutures.

The fact that PLG is already FDA approved for other applications should facilitate translating the research to patients, Shea noted. Miller and Shea tested nanoparticles of various sizes and discovered that 500 nanometers was most effective at modulating the immune response.

"We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks," Miller said. "We prevented any future relapses for up to 100 days, which is the equivalent of several years in the life of an MS patient."

Shea and Miller also are currently testing the nanoparticles to treat Type one diabetes and airway diseases such as asthma.

Nanoparticles Fool Immune System

In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.

"The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system," said Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the National Institutes of Health, which supported the research. "This collaborative effort between expertise in immunology and bioengineering is a terrific example of the tremendous advances that can be made with scientifically convergent approaches to biomedical problems."

"We are proud to share our expertise in therapeutics development with Dr. Stephen Miller's stellar team of academic scientists," said Scott Johnson, CEO, president and founder of the Myelin Repair Foundation. "The idea to couple antigens to nanoparticles was conceived in discussions between Dr. Miller's laboratory, the Myelin Repair Foundation's drug discovery advisory board and Dr. Michael Pleiss, a member of the Myelin Repair Foundation's internal research team, and we combined our efforts to focus on patient-oriented, clinically relevant research with broad implications for all autoimmune diseases. Our unique research model is designed to foster and extract the innovation from the academic science that we fund and transition these technologies to commercialization. The overarching goal is to ensure this important therapeutic pathway has its best chance to reach patients, with MS and all autoimmune diseases."

Journal Reference:

1.      Daniel R Getts, Aaron J Martin, Derrick P McCarthy, Rachael L Terry, Zoe N Hunter, Woon Teck Yap, Meghann Teague Getts, Michael Pleiss, Xunrong Luo, Nicholas JC King, Lonnie D Shea, Stephen D Miller. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nature Biotechnology, 2012; DOI:10.1038/nbt.2434

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The above story is reprinted from materials provided by Northwestern University, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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DNA Packaging Discovery Reveals Principles by Which CRC Mutations May Cause Cancer (Eagle Group- Nov 18, 2012)

Fundamental understanding about how DNA works will produce a "180-degree change in focus" for researchers who study how gene packaging regulates gene activity, including genes that cause cancer and other diseases.

The discovery, by Bradley R. Cairns, PhD, Senior Director of Basic Science at HCI and a professor in the Department of Oncological Sciences, is reported in this week's online issue of the journal Nature.

Cairns's research focuses on chromatin remodeling complexes (CRCs), which are cellular protein complexes that behave like motors, expanding or compacting different portions of DNA to either express or silence genes, respectively. Before, scientists thought that the motor within CRCs waits at rest until it receives instructions. Cairns and co-author Cedric R. Clapier show that the motor within a key CRC responsible for gene packaging and assembly is intrinsically turned on, and instead requires specific instructions to turn it off.

"Many articles in the research literature show that CRCs are mutated in cancer cells. They are intimately involved in regulating gene expression -- responsible for correctly packaging genes that control growth proliferation and for unpackaging tumor suppressors," said Cairns. "This research reveals principles by which CRC mutations could cause cancer."

Chromosomes are made of long DNA strands compressed around nodes of protein called nucleosomes; when DNA is compressed, the genes in that area are turned off. Some CRCs, called disassembly CRCs, act as motors that unwind sections of DNA chains, making genes active for a given cell process. Another type, called assembly CRCs, rewinds the DNA chain, recompressing it when the process is complete. The unwind-rewind cycle is repeated continuously throughout a cell's life.

In this study, Cairns and Clapier focused on assembly CRCs. "Before this research, we thought that the motor was off unless a protein coming from another part of the cell turned it on," said Cairns. "Researchers have been searching for the switch by looking at the CRC motor to see what binds to it.

"As it turns out, we discovered that the CRC motor already carries on its flank a 'switch' that inhibits its action until a marker sequence, located on the nucleosome, is encountered. The marker flips the inhibitor switch and allows the CRC to crank the DNA chain back around the nucleosome, promoting gene packaging and silencing" Cairns said. "Our results change where future researchers should be looking to understand how CRCs are regulated -- not at the CRC motor itself, but at the 'switches' that flank the motor."

The study also describes a measuring function on the CRC that checks for the correct distance between one nucleosome and the next, telling the motor to switch off at the proper time, a function needed for gene silencing.

Cairns's lab will now examine this same switching concept in disassembly remodelers. "There are additional remodeler families with alternative functions, like DNA repair," said Cairns. "We think this concept will apply to them as well."

This research was supported by funding from the National Institutes of Health (GM60415 and CA042014) and from the Howard Hughes Medical Institute.

Journal Reference:

1.      Cedric R. Clapier, Bradley R. Cairns. Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 2012; DOI: 10.1038/nature11625

Source:

The above story is reprinted from materials provided by University of Utah Health Sciences.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

 

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New Way for Antibiotic Resistance to Spread (Eagle Group- Nov 18, 2012)

Washington State University researchers have found an unlikely recipe for antibiotic resistant bacteria.

"I was surprised at how well this works, but it was not a surprise that it could be happening," says Doug Call, a molecular epidemiologist in WSU's Paul G. Allen School for Global Animal Health. Call led the research with an immunology and infectious disease Ph.D. student, Murugan Subbiah, now a post-doctoral researcher at Texas A & M. Their study appears in a recent issue of the online journal PLOS ONE.

While antibiotics have dramatically reduced infections in the past 70 years, their widespread and often indiscriminate use has led to the natural selection of drug-resistant microbes. People infected with the organisms have a harder time getting well, with longer hospital stays and a greater likelihood of death.

Animals are a major source of resistant bugs, receiving the bulk of antibiotics sold in the U.S.

The scientists focused on the antibiotic ceftiofur, a cephalosporin believed to be helping drive the proliferation of resistance in bacteria like Salmonella and E. coli. Ceftiofur has little impact on gut bacteria, says Call.

"Given that about 70 percent of the drug is excreted in the urine, this was about the only pathway through which it could exert such a large effect on bacterial populations that can reside in both the gut and the environment," he says.

Until now, conventional thinking held that antibiotic resistance is developed inside the animal, Call says.

"If our work turns out to be broadly applicable, it means that selection for resistance to important drugs like ceftiofur occurs mostly outside of the animals," he says. "This in turn means that it may be possible to develop engineered solutions to interrupt this process. In doing so we would limit the likelihood that antibiotic resistant bacteria will get back to the animals and thereby have a new approach to preserve the utility of these important drugs."

One possible solution would be to find a way to isolate and dispose of residual antibiotic after it is excreted from an animal but before it interacts with soil bacteria.

The WSU experiments were performed in labs using materials from dairy calves. Researchers must now see if the same phenomenon takes place in actual food-animal production systems.

Funding for the study included grants from the National Institutes of Health, the WSU College of Veterinary Medicine's Agricultural Animal Health Program, the WSU Agricultural Research Center, and Call's Caroline Engle professorship in research on infectious diseases.

Other researchers were Devandra Shah and Tom Besser, both in WSU's Department of Veterinary Microbiology and Pathology and the Allen School, and Jeffrey Ullman at the University of Florida in Gainesville.

Journal Reference:

1.      Murugan Subbiah, Devendra H. Shah, Thomas E. Besser, Jeffrey L. Ullman, Douglas R. Call. Urine from Treated Cattle Drives Selection for Cephalosporin Resistant Escherichia coli in Soil. PLoS ONE, 2012; 7 (11): e48919 DOI: 10.1371/journal.pone.0048919

 

Source:
The above story is reprinted from materials provided by Washington State University. The original article was written by Eric Sorensen.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: Views expressed in this article do not necessarily reflect those of Eagle Group or its staff.

 

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New Tools Developed to Better Treat ADHD Patients in Early Stages (Eagle Group- Nov 17, 2012)

Mayo Clinic researchers are presenting new findings on the early treatment of child and adolescent attention deficit hyperactivity disorder this week at the American Academy of Childhood and Adolescent Psychiatry annual meeting in San Francisco. Find out…..

In the first study, Mayo Clinic researchers required parents and teachers of children coming in for their first ADHD consultation, defined by some combination of problems such as difficulty sustaining attention, hyperactivity and impulsive behavior, consultations to complete extensive background forms and analysis. By offering incentives and stressing the importance of being prepared for the first consultation, clinicians were able to boost parent and teacher compliance from 25 to 90 percent at the Mayo Clinic Child and Adolescent ADHD Clinic. As a result, researchers have been able to better recommend treatment and therapy right off the bat.

"I'd compare treating a child with ADHD for the first time to consulting with someone who has type II diabetes -- we need to measure a diabetic patient's blood sugar level before we can properly treat them," says study lead author Jyoti Bhagia, M.D., a Mayo Clinic psychiatrist. "The same goes for ADHD. The more we know about children in the early stages of treatment, the more quickly we can get them the help they need."

In the second study, Mayo Clinic researchers gave 75 patients with ADHD at the Mayo Clinic Child and Adolescent ADHD Clinic a written, subjective evaluation to test for oppositional defiance disorder, a persistent pattern of tantrums, arguing, and angry or disruptive behavior toward authority figures.

They found that the test was far better able to pick up whether the child had the disorder than an anecdotal physician diagnosis. Of the 75 patients in the study, 27 percent, or less than a third, were diagnosed with oppositional defiance disorder by their providers. After taking the subjective test, 48 percent tested positive for oppositional defiance disorder. That shows the presence of oppositional defiance disorder with ADHD is underdiagnosed and children may not be receiving the behavioral treatment they need.

Children who have both ADHD and oppositional defiance disorder benefit from a combination of medication and behavioral therapy, says Dr. Bhagia.

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The above story is reprinted from materials provided by Mayo Clinic.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Enhancing Breast Cancer Detection: Computer Algorithm Analyzes Thermal Images of Breasts (Eagle Group- Nov 17, 2012)

Straightforward imaging with an infrared, thermal, camera for detecting breast cancer early without the discomfort or inconvenience of mammography or biomolecular tests.

Tiago Borchartt of the Federal Fluminense University in Brazil and colleagues explain how breast thermography has up to now achieved an average sensitivity and specificity or approximately 90 percent for the detection of malignant tissue. The advantages of the technique are that it is painless, requires no contact between patient and instrumentation and is entirely non-invasive. However, a 90 percent accuracy rate implies that there is a lot of room for improvement before such a technique could become a mainstream clinical diagnostic for the early stages of breast cancer.

The team has developed new software that allows them to acquire thermal images into a computer database and so be used to help with diagnosis after the automatic extraction of the regions of interest. The same tool combines storage with feature extraction and recognition. The approach can detect the presence of problems using symmetric analysis and numerical simulations using finite element analyses allows it to analyze the relationships between internal temperature and the temperature on the breast surface during image acquisition.

So far, the researchers have tested their approach on a limited number of thermal images from 28 patients: four healthy patients, eight with cysts, eleven patients with fibroadenoma and five with carcinoma. They were able to improve the accuracy of breast thermography using their approach to 96%. The next step will be to test this in larger group of at least 2000 patients. That future project has already been approved by the ethical committee of the University Hospital of UFF.

Journal Reference:

Tiago B. Borchartt; Roger Resmini; Leonardo S. Motta; Esteban W.G. Clua; Aura Conci; Mariana J.A. Viana; Ladjane C. Santos; Rita C.F. Lima; Angel Sanchez.Combining approaches for early diagnosis of breast diseases using thermal imaging. International Journal of Innovative Computing and Applications, 2012; 4 (3/4) [link]

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The above story is reprinted from materials provided by Inderscience Publishers, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Hepatitis C Treatment's Side Effects Can Now Be Studied in the Lab (Eagle Group- Nov 17, 2012)

Study the new method which helps to understand failures of hepatitis C antiviral drug (in clinical trials) and also help in identifying the medication that eliminates all adverse effects, thanks to a research team led by Craig Cameron, the Paul Berg Professor of Biochemistry and Molecular Biology at Penn State University. 

The team's findings, published in the current issue of the journal PLOS Pathogens, may help pave the way toward the development of safer and more-effective treatments for hepatitis C, as well as other pathogens such as SARS and West Nile virus.

First author Jamie Arnold, a research associate in Cameron's lab at Penn State, explained that the hepatitis C virus (HCV), which affects over 170,000,000 people worldwide, is the leading cause of liver disease and, although antiviral treatments are effective in many patients, they cause serious side effects in others. "Many antiviral medications for treating HCV are chemical analogs for the building blocks of RNA that are used to assemble new copies of the virus's genome, enabling it to replicate," he said. "These medications are close enough to the virus's natural building blocks that they get incorporated into the virus's genome. But they also are different in ways that lead to the virus's incomplete replication. The problem, however, is that the medication not only mimics the virus's genetic material, but also the genetic material of the patient. So, while the drug causes damage to the virus, it also may affect the patient's own healthy tissues."

A method to reveal these adverse side effects in the safety of a laboratory setting, rather than in clinical trials where patients may be placed at risk, has been developed by the research team, which includes Cameron; Arnold; Suresh Sharma, a research associate in Cameron's lab; other scientists at Penn State; and researchers from other academic, government, and corporate labs. "We have taken anti-HCV medications and, in Petri dishes and test tubes, we have shown that these drugs affect functions within a cell's mitochondria," Cameron explained. "The cellular mitochondria -- a tiny structure known as 'the powerhouse of the cell' that is responsible for making energy known as ATP -- is affected by these compounds and is likely a major reason why we see adverse effects." Cameron noted that scientists have known for some time that certain individuals have "sick" mitochondria. Such individuals are likely more sensitive to the mitochondrial side effects of antiviral drugs.

"We know that antiviral drugs, including the ones used to treat HCV, affect even normal, healthy mitochondria by slowing ATP output," Arnold added. "While a person with normal mitochondria will experience some ATP and mitochondrial effects, a person who is already predisposed to mitochondrial dysfunction will be pushed over the 'not enough cellular energy' threshold by the antiviral drug. The person's mitochondria simply won't be able to keep up."

One of the problems with clinical trials, Arnold explained, is that a drug may be shown to be quite effective but, if even a miniscule percentage of patients have side effects, the U.S. Food and Drug Administration is obligated to put the trial on hold or stop the trial altogether. This possibility makes drug companies reluctant to invest money in drug trials after an adverse event has been observed, even when the drugs could still help millions of people. The researchers hope that their methods eventually will become a part of the pre-clinical development process for this class of antiviral drugs. "If we can show, in the lab, that a drug will cause side effects, then these compounds will not enter lengthy, expensive clinical trials and cause harm to patients " he said. "What's more, a drug company can invest its money more wisely and carefully in drug research that will produce safe and effective products. Better and more-willing investments by drug companies ultimately will help patients, because resources will be spent developing drugs that not only work, but that are safe for all patients."

Cameron added that the next step for his team is to identify the genes that make some individuals respond poorly to these particular antiviral treatments. "By taking blood samples from various patients and using the new method to test for toxicity in the different samples, we hope to discover which individuals will respond well and which will experience mitochondrial reactions, based on their genetic profiles," he said. "That is, we hope to use this method as a step toward truly personalized medicine, opening the door to pre-screening of patients so that those with mitochondrial diseases can be treated with different regimens from the start."

The team members also hope their method will be a means to study toxicity and side effects in other diseases. "Specifically, our technology will illuminate toxicity of a particular class of compounds that interrupts viral RNA synthesis," Cameron said. "While this class of compounds currently is being developed for treatment of HCV, a wide range of other RNA viruses, including West Nile virus, Dengue virus, SARS coronavirus, and perhaps even the Ebola virus, could be treated using this class of compounds as well."

In addition to Cameron, Arnold, and Sharma, other researchers who contributed to this study include Eric D. Smidansky from Penn State; Joy Y. Feng, Adrian S. Ray, Aesop Cho, Jason Perry, Jennifer E. Vela, Yeojin Park, Yili Xu, Yang Tian, Darius Babusis, Ona Barauskus, and Weidong Zhong from Gilead Sciences, Inc.; Maria L. Kireeva and Mikhail Kashlev from the Frederick National Laboratory for Cancer Research; Blake R. Peterson from the University of Kansas; and Averell Gnatt from the University of Maryland School of Medicine.

The research was funded by the National Institutes of Health and a Penn State Paul Berg Endowment.

Journal Reference:

1.      Jamie J. Arnold, Suresh D. Sharma, Joy Y. Feng, Adrian S. Ray, Eric D. Smidansky, Maria L. Kireeva, Aesop Cho, Jason Perry, Jennifer E. Vela, Yeojin Park, Yili Xu, Yang Tian, Darius Babusis, Ona Barauskus, Blake R. Peterson, Averell Gnatt, Mikhail Kashlev, Weidong Zhong, Craig E. Cameron. Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependent Nuclear Transcription to Antiviral Ribonucleosides. PLoS Pathogens, 2012; 8 (11): e1003030 DOI:10.1371/journal.ppat.1003030

Source:

The above story is reprinted from materials provided by Penn State. The original article was written by Katrina Voss.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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