Friday, February 10, 2012

Site Search

Archive for the ‘DNA Reasearch’ Category

Research at A&M and Scripps finds HIV-killing compound

COLLEGE STATION - A powerful topical preventative for HIV, the virus that causes AIDS, could be a step closer to clinical trials, thanks to a newly discovered molecular compound that research at Texas A&M University and the Scripps Research Institute shows dissolves the virus on contact.

The ability of the synthetic compound known as “PD 404,182″ to break apart the AIDS-causing virus before it can infect cells was discovered by Zhilei Chen, assistant professor in the university’s Artie McFerrin Department of Chemical Engineering, and her team of researchers. Their findings appear in the November online edition of “Antimicrobial Agents and Chemotherapy,” a journal of the American Society for Microbiology.

“This is a virucidal small-molecule compound, meaning that it has the ability to kill a virus; in this case that virus is HIV,” Chen says.

“Basically, it acts by breaking the virus open. We found that when HIV comes in contact with this compound, it breaks open and loses its genetic material. In a sense, the virus ‘dissolves,’ and its RNA becomes exposed.

Since RNA is pretty unstable, once it is exposed it’s gone very quickly and the virus is rendered non-infectious.”

In other words, the compound works by quickly ripping open the virus before it can inject its genetic material into a human cell. What’s more – and perhaps even more important – the compound, Chen explains, achieves this by acting on something within the virus other than its viral envelope protein, meaning that the virus can’t alter its proteins to bolster its resistance – something that’s made HIV notoriously difficult to treat.

“We believe this compound is not working on the viral protein of the viruses but on something else common in all the viruses on which we tested it – some cellular material common in these viruses,” Chen notes. “Because this compound is acting on a component that is not encoded by the virus, it will be difficult for the virus to evolve resistance against this compound.”

While not a cure for HIV, the compound demonstrates significant potential for use as a preventative, specifically in the form of a topical gel that could be applied in the vaginal canal, Chen explains.

“We conducted a number of tests to demonstrate that this compound remains active in vaginal fluid and is not rendered ineffective,” Chen says. “In the form of a vaginal gel, the compound would serve as a barrier, acting almost instantaneously to destroy the virus before it could infect a cell, thereby preventing HIV transmission from one person to another.”

Surprisingly, Chen and her team did not set out to discover an HIV preventative. Instead, they were conducting screenings of molecules for use in potential drug therapies targeting hepatitis C virus, which causes the dangerous and often fatal disease of the liver. Employing a screening system developed by Chen, the team screened thousands of molecular compounds, in search of those that could block aspects of the HCV life cycle.

During the course of the screenings, the team made an interesting discovery

- not only was PD 404,182 an HCV inhibitor, it also worked on lentiviruses (the group’s negative control in its experimental procedures). Intrigued by that finding, Chen then tested PD 404,182 on HIV, which itself is a lentivirus and found the compound to be even more effective on HIV than on HCV.

“We believe PD 404,182 acts through a unique and important mechanism,” Chen notes. “Most of the known virucidal compounds interact with the virus membrane, but our compound does not appear to interact with the virus membrane. Instead, it bypasses interaction with the membrane and still compromises the structural integrity of the virus.”

The ability of the compound to avoid interaction with the virus membrane is important because human cells have similar membranes, Chen notes. If the compound were to disrupt the structure of the virus membrane, it could also disrupt and ultimately kill human cells. PD 404,182 doesn’t interact with these membranes and is therefore a more attractive option for clinical treatment, Chen says.

As is the case with any potential pharmaceutical, several key steps are still needed before it winds up on drug store shelves. In addition to several rounds of animal studies to ensure the compound is safe for humans, further collaborations with chemists are needed to continue to improve the efficiency of the compound. Chen says. What’s more, Chen also plans to further explore the mechanism by which PD 404,182 breaks apart HIV.

This work is collaboration between Chen’s team, consisting of graduate students Ana Maria Chamoun and Rudo Simeon, postdoctoral associate Karuppiah Chockalingam, and Professor Philippe Gallay’s team at the Scripps Research Institute.

Source: http://www.kxxv.com/story/16095021/research-at-am-and-scripps-finds-hiv-killing-compound

FDA Clears Abbott’s Confirmatory Chagas Disease Assay

FDA approved Abbott’s in vitro enzyme strip assay for Chagas disease. The Abbott ESA Chagastest detects antibodies to the causative pathogen Trypanosoma cruzi in serum or plasma samples. It is indicated for use as an additional, more specific test on human samples that have been found to be repeatedly reactive using a licensed screening test.

The T. cruzi parasite is transmitted through contact with the feces of an infected triatomine bug, but infection can also occur congenitally, through transfusions of contaminated blood products, or through an organ transplant from an infected donor.

U.S. Centers for Disease Control and Prevention (CDC) estimates suggest that as many as 11 million people worldwide are infected with Chagas disease, including over 300,000 in the U.S. alone. Concerns about Chagas disease transmission through blood led FDA to implement mandatory Chagas disease screening of donated blood back in 2007. “The new Abbott ESA Chagas test provides organizations that screen blood with an approved testing method help the blood supply safe and enable them to confidently counsel infected donors,” remarks John Coulter, divisional vp for Abbott’s diagnostics business.

Source: http://www.genengnews.com/gen-news-highlights/fda-clears-abbott-s-confirmatory-chagas-disease-assay/81245981/

Study: Shark Chemical May Protect Humans Against Viruses

A chemical derived from sharks could help protect humans against viral infections such as hepatitis, American research out Tuesday showed.

Scientists found that a chemical called squalamine demonstrated effective antiviral activity against a range of human viruses from yellow fever to hepatitis B, C and D, in both lab and animal experiments.

As the chemical has already been used in human clinical trials for the treatment of cancer and eye disorders, it means it could quickly be tested as a new drug treatment for viral diseases, researchers at Georgetown University Medical Center, Washington, said.

“To realize that squalamine potentially has broad antiviral properties is immensely exciting, especially since we already know so much from ongoing studies about its behavior in people,” lead researcher Professor Michael Zasloff, said.

“Squalamine appears to protect against viruses that attack the liver and blood tissues, and other similar compounds that we know exist in the shark likely protect against respiratory viral infections, and so on,” he added.

Zasloff believes the research, published in the “Proceedings of the National Academy of Sciences” journal, also explains the mystery of how sharks, which have a very primitive immune system, can so effectively fight the viruses that plague other living creatures.

He continued, “We may be able to harness the shark’s novel immune system to turn all of these antiviral compounds into agents that protect humans against a wide variety of viruses. That would be revolutionary. While many antibacterial agents exist, doctors have few antiviral drugs to help their patients, and few of those are broadly active.”

Source: http://www.foxnews.com/health/2011/09/20/study-shark-chemical-may-protect-humans-against-viruses/

Ark to Manufacture PsiOxus’ IV-Administered Oncolytic Virus for Clinical Trials

    Ark Therapeutics negotiated a manufacturing partnership with PsiOxus Therapeutics for the latter’s ColoAd1 candidate for the treatment of colorectal cancer. Under terms of the agreement Ark will work with PsiOxus to generate an IV formulation of the adenovirus-based oncolytic product using its suspension-based single-use system (ATOSUS) for toxicological and Phase I/II clinical studies.

    ColoAd1 is an Ad3/Ad11p hybrid, designed as a broad-spectrum anticancer therapeutic capable of destroying tumor cells at minute concentrations, but with minimal damage to healthy tissue. The oncolytic virus has been generated using the evolutionary principle of natural selection, to generate a candidate that PsiOxus claims demonstrates anticancer potency at 0.1–10 femtomolar concentration, including activity against drug-resistant cancers. The initial target indications for ColoAd1 will be metastatic colorectal cancer and primary hepatic cellular carcinoma.

    The evolutionary approach used to generate ColoAd1 involves generating a chimeric adenovirus library by homologous recombination under atypical conditions of super-infection, PsiOxus explains. Multiple rounds of selection are subsequently carried out to identify strains with a tumor-dependent phenotype that also rapidly killed tumor cells. Candidate oncolytic viruses are then screened on normal cells to select a candidate with optimal therapeutic index.

    PsiOxus was established in December 2010 through the merger of Myotec Therapeutics and Hybrid BioSystems. The ColoAd1 candidate originated at Hybrid Biosystems, a firm initially established to exploit viruses as therapeutics. The candidate was developed by Hybrid in collaboration with Bayer Schering. Hybrid Biosystems also developed the PolyStar vaccine vector system, and PolyMap adjuvant/immunotherapeutics platform, both of which PsiOxus inherited when it was formed last year.

    PsiOxus’ lead clinical-stage compound, MT-102, is a small-molecule anabolic catabolic transforming agent, which is currently undergoing a placebo-controlled Phase II trial as a treatment for disease-related cachexia. MT-102 was originally developed by Myotec, itself an Imperial College London spin-out established to progress work by university scientists on the underlying mechanisms of cachexia. PsiOxus says promising preclinical results from in vivo studies evaluating MT-102 against age-related sarcopenia will also be followed up through future clinical studies.

    Source: http://www.genengnews.com/gen-news-highlights/ark-to-manufacture-psioxus-iv-administered-oncolytic-virus-for-clinical-trials/81245663/

Clinical Successes and New Technologies Revive Gene Therapy

    The prospect of curing human diseases by replacing a disease-related gene with a normal version remains the ultimate goal of gene therapy. But in its early days, attempts at gene therapy met with unpredictable and occasionally fatal outcomes. The field sustained a serious setback in 2000 following the death of 18-year old Jesse Gelsinger after receiving gene therapy to treat orinthine trascarbamlase deficiency (OTCD), a rare metabolic disorder that prevents the body from breaking down ammonia.

    Gene therapy took another blow in September 2003, when the FDA placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells. The agency was responding to the development of a leukemia-like disorder that developed in a three-year-old boy following successful gene therapy for to X-linked severe combined immunodeficiency disease (X-SCID). Subsequently, the disease developed in three children, one of whom died from it.

    Now, bolstered by the development of enabling technologies and recent clinical successes, gene therapy is making a significant comeback. Effective gene delivery has been established in multiple formats including direct DNA delivery, genetically engineered autologous cells, and specifically targeted gene modification or insertion.

    Adrenoleukodystrophy

    In 2009, international teams of researchers reported the successful treatment of two children suffering from adrenoleukodystrophy (ALD). ALD is a severe hereditary condition caused by mutations in ABCD1 gene, which encodes the adrenoleukodystrophy protein (ALDP), a protein involved in fatty acid degradation.

    Over the course of the disease, afflicted individuals steadily lose the myelin sheath that surrounds nerve cells. Myelin loss results in loss of nerve function, leading to increasing physical and mental disability. X-linked ALD, the most common form of the disease, affects boys as early as age six, with death usually occurring before the patients reach adolescence.

    While ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT), finding correctly matched donors and the inherent dangers in the procedure present problems.

    Investigators in France reported successful treatment of two ALD patients for whom there were no matched donors. They first removed CD34+ cells, then transfected the cells ex vivo with a lentiviral vector encoding the wild-type correct form of the gene encoding ALDP, and finally re-infusing them into the patients after they had received myeloablative treatment.

    Over a span of 24 to 30 months of follow-up, the authors said, they could detect polyclonal reconstitution, with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein.

    Beginning 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT. Thus, the authors said, lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD.

    Leber Congenital Amaurosis

    Another successful area for gene therapy has been Leber congenital amaurosis (LCA), a heritable form of progressive blindness. LCA, the result of a mutation in the RPE65 gene, may be treatable by introducing a normal copy of the mutated gene directly into the retinas of affected individuals.

    Normally, the RPE65 protein converts dietary vitamin A into a retina-specific form of vitamin A needed for rhodopsin formation. Rhodopsin is a visual pigment that absorbs light after it enters the eye, and it requires the RPE65 protein to regenerate after light exposure. Therefore, mutations in the RPE65 gene seen in LCA disrupt the visual cycle and prevent normal vision.

    Several groups have reported progress in treating the disease in individuals with the specific mutation. In 2008, these researchers administered subretinal injections of recombinant adeno-associated virus (AAV) vector expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter.

    Investigators concluded that the safety, extent, and stability of improvement in vision in all patients support the use of AAV-mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain.

    HIV/AIDS

    Apart from advancements in DNA delivery and in vectors for gene delivery into patients’ cells, zinc finger nuclease technology may prove truly transformative to gene therapy in general. Zinc finger nucleases (ZFNs) are synthetic proteins consisting of an engineered zinc finger DNA-binding domain fused to the cleavage domain of a restriction endonuclease. These engineered molecules allow cellular DNA to be cut at specific points, with gene modification then occurring via the cell’s own natural repair mechanisms. They may also allow the insertion of entire genes at desired cleavage sites to replace missing or mutated genes.

    Sangamo and colleagues from the University of Pennsylvania announced positive preliminary data from their Phase I trial being conducted in HIV-infected immunologic nonresponders. The patients enrolled in this study were HIV-infected individuals on highly active antiretroviral therapy with undetectable levels of virus but low T-cell counts.

    The investigators used zinc fingers custom-designed to bind to specific DNA sequences in the CCR5 gene in HIV-infected patients’ T cells. The zinc finger proteins act as molecular scissors, bringing a DNA enzyme to the CCR5 gene to cut its sequence. During the repair process, a new mutation arises in the CCR5 protein, rendering it nonfunctional. Since the HIV virus uses the normal, unmodified version of CCR5 to gain access to T cells, the engineered cells became completely resistant to infection.

    The data showed that a single infusion of the engineered cells was well tolerated, and the CCR5-modified cells successfully engrafted in all of the patients. The treatment also resulted in a durable improvement in total CD4+ T-cell counts in five of six patients analyzed.

    The ZFN-CCR5-modified cells also exhibited normal T-cell growth kinetics and trafficking and underwent selective expansion in the gut mucosa, a major reservoir of virus in the body, suggesting, as predicted, that the cells were resistant to HIV infection.

    Sangamo’s Philip Gregory, CSO and vp, research, told GEN that the goal of developing the company’s zinc finger nuclease program “has been to give investigators the ability to perform precision engineering directly on the genome itself.”

    In the HIV application, he pointed out, no new DNA is being introduced. “We are really introducing a mutation ourselves just with the nucleases. We were able to do this because DNA repair mechanisms themselves are error prone. When the cells repair the break generated by the ZFN, the process occurs without error checking and mutations are introduced specifically at the site of the break. We can use this to achieve one desired outcome, knockout of the gene that’s been cleaved by the nuclease—in this case, the CCR5 gene. When the cell repairs it, it will create mutations.”

    In explaining the production process for the autologous cells carrying the mutated CCR5 gene, Gregory said that the cells are collected from patients and sent to a processing facility, where they are exposed to the ZFN. The cells are expanded, and then re-infused into the patient, where they engraft, expand in the patients, and get trafficked to the normal place in the body.

    “These cells are noninfectable by HIV,” Gregory said. He further explained that “just by protecting T cells, we aimed to create a reservoir of these cells that couldn’t be infected. These cells protect against loss of cells in HIV-infected patients.”

    Gregory emphasized that CCR5 itself as a target “is one of the few situations in which we know the biology of the protein from the situation that exists in the natural population of patients. Patients with the Delta 32 CCR5 mutation don’t have the receptor on their cells and are completely normal but are resistant to infection.

    “It turns out,” he said, “that an important feature of that mutation is that it eliminates CCR5 completely, giving rise to cells with no receptor on their surfaces.”

    Sangamo says it is testing its product across a full range of HIV patients including those for whom current drug regimens are failing. “We are making good progress and are letting the data tell us where to focus our further clinical trials.”

    All this progress, investigators point out, represents the culmination of years of experience, encompassing multiple disciplines from molecular biology through clinical science. And hopefully as positive clinical results continue to emerge, effective gene therapy, in whatever format, will become a real therapeutic option for intractable human diseases.

    Source: http://www.genengnews.com/analysis-and-insight/clinical-successes-and-new-technologies-revive-gene-therapy/77899451/

Genetic Link Predisposes to Mesothelioma

An investigation led by scientists at the University of Hawaii Cancer Center, Honolulu, and Fox Chase Cancer Center, Philadelphia has identified germline mutations in the BAP1 gene that predispose individuals to malignant mesothelioma. The research, published online yesterday in Nature Genetics, describes two U.S. families with a high incidence of mesothelioma, as well as other cancers, associated with mutations of the gene BAP1 [1].

Scientists have discovered that individuals who carry a mutation in a gene called BRCA1-associated protein 1 (BAP1) are susceptible to developing two forms of cancer — mesothelioma and melanoma of the eye. When these individuals are exposed to asbestos or similar mineral fibers, their risk of developing mesothelioma, an aggressive cancer of the lining of the chest and abdomen, may be markedly increased.

Mesothelioma tumors are typically associated with asbestos and erionite exposure. Erionite is a naturally occurring mineral fiber similar to asbestos that is found in rock formations and volcanic ash. Deposits have been located in at least 12 states. However, unlike asbestos, erionite is not currently regulated by the U.S. Environmental Protection Agency as one of the six asbestos fibers [2]. Only a small percentage of people exposed to asbestos or erionite actually develop mesothelioma.

Mesothelioma is one of the deadliest forms of cancer, killing approximately 3,000 people each year in the United States, with half of those diagnosed dying within one year. Moreover, rates of new cases of mesothelioma in parts of the world, including Europe and China, have risen steadily over the past decade.

Michele Carbone, M.D., Ph.D., study co-leader and director of the University of Hawaii Cancer Center, said [3]:

This discovery is a first step in understanding the role of the BAP1 gene and its potential utility when screening for mutations in those at high risk. Identifying people at greatest risk for developing mesothelioma, especially those exposed to dangerous levels of asbestos and erionite worldwide, is a task made easier by virtue of this discovery.

Joseph R. Testa, Ph.D., study co-leader and Carol and Kenneth E. Weg chair in Human Genetics at Fox Chase Cancer Center, added [3]:

This is the first study to demonstrate that individual genetic makeup can greatly influence susceptibility to mesothelioma. People exposed to dangerous levels of asbestos or erionite, those with a strong family history of mesothelioma, or those who have been previously diagnosed with a rare tumor of the eye known as uveal melanoma, may benefit from this new discovery.

The researchers focused on two US mesothelioma families — one in Wisconsin and one in Louisiana — in which members were not exposed to asbestos or erionite. Family members developed a number of malignancies, including breast, ovarian, pancreatic and renal cancers, although mesothelioma predominated.

The scientists suspected that mutations in the BAP1 gene might underlie mesothelioma in people with a strong family history of the disease after noticing genetic changes in or near other stretches of DNA where the BAP1 gene is located. Looking more closely at two families with unusually high rates of mesothelioma, they saw that every person who had provided a sample and had developed mesothelioma or melanoma of the eye also carried mutations in the BAP1 gene. Further study led to sequencing the gene in 26 individuals who had developed mesothelioma but did not have a family history of the disease. Tumors from about 25 percent of this group carried mutations in the BAP1 gene, and in two cases the mutations were inherited. Both of the individuals with inherited mutations had previously developed melanoma of the eye.

The researchers hypothesize that when individuals with BAP1 mutations are exposed to asbestos, mesothelioma predominates over melanoma of the eye. Alternatively, the BAP1 mutation alone may be sufficient to cause mesothelioma, providing a cause for tumors that arise spontaneously without previous environmental exposure.

Source: http://www.highlighthealth.com/research/genetic-link-predisposes-to-mesothelioma/

Adding caffeine to sunscreen could guard against skin cancer

Scientists have worked out how caffeine might protect against certain skin cancers – a finding that could lead to better sunscreens.

The research, conducted in mice, suggests that caffeine changes the activity of a gene involved in the destruction of cells that have DNA damage and are therefore more likely to become cancerous. The scientists said this may lead to new ways of preventing skin cancer, though other experts cautioned that it did not mean coffee lovers were better protected against the disease.

Skin cancer is a common disease. According to Cancer Research UK, around 100,000 cases of non-melanoma were registered in the UK in 2008, and just under 12,000 cases of the more dangerous malignant melanoma. These cancers can be caused by over-exposure to ultraviolet light from the sun, which can damage the DNA of skin cells, leading to errors when the cells divide.

The overall protective role of caffeine against cancers has been noted in previous studies, but Allan Conney of the department of chemical biology at Rutgers University in New Jersey wanted to find the specific molecular mechanisms behind it. He suspected that the response might involve a gene called ATR, which is suppressed when caffeine molecules are around. This suppression encourages the death of DNA-damaged cells.

Conney tested the idea by creating genetically modified mice whose ATR genes were deficient and exposing them to ultraviolet light until they developed skin cancer. After 19 weeks of UV exposure, he found that these mice developed 69% fewer tumours than those that had fully functioning ATR genes. In addition, tumours in the GM mice developed three weeks later than in standard mice.

After 34 weeks of UV exposure, all the mice had developed tumours, mainly a type of non-melanoma cancer called squamous cell carcinoma (SCC). The results were published on Monday in the Proceedings of the National Academy of Sciences.

“All of this suggests the possibility that caffeine, possibly [applied to the skin], would have an inhibitory effect on sunlight-induced skin cancer,” said Conney. “In addition to the effects on the ATR pathway, caffeine also has sunscreening properties.”

SCCs are less common than the other type of non-melanoma cancer, called basal cell carcinomas, but it’s the former that are more dangerous. “People rarely die from basal cell carcinomas, but you need more invasive cutting to get it out,” said Conney. “There’s more disfiguration with basal cell than squamous cell. It’s the squamous cell cancers that can metastasise and are more dangerous.”

Jessica Harris, a health information manager at Cancer Research UK, pointed out that Conney’s study examined how caffeine affected genes when it was directly applied to the skin, rather than ingested. “It didn’t look at the effects of drinking coffee, so doesn’t tell us whether or not this could reduce the risk of skin cancer,” she said.

Studies looking at coffee consumption and cancer in large groups of people have provided mixed results, she added. “Some have found that coffee drinking may slightly reduce the risk of certain types of cancer, but the evidence is not yet strong enough to be certain, and these effects tend to be seen among people who drink very large amounts.”

The best way to reduce the risk of skin cancer, said Harris, “is to enjoy the sun safely, taking care not to burn by using a combination of shade, clothing and sunscreen.”

Dot Bennett, a professor of cell biology at St George’s, University of London, said that any move to add caffeine or related molecules to sunscreens should be undertaken with care. “First one might want to check there is no adverse effect of caffeine on the incidence of other cancers, especially melanoma (pigmented skin cancer), which kills over four times as many people as [squamous cell carcinoma]. But caffeine lotion might promote tanning a little, since this family of molecules stimulates pigment cells to make more pigment.”

Source: http://www.guardian.co.uk/science/2011/aug/15/adding-caffeine-sunscreen-skin-cancer

Blood Antibody May Signal Start of Ovarian Cancer

WEDNESDAY, Aug. 17 (HealthDay News) — Researchers have found an antibody that might someday be useful in identifying women who have a higher risk of ovarian cancer, or possibly diagnosing early ovarian cancer.

Click here to find out more!

This particular antibody, which was detected in blood, develops as an immune system response to a protein called mesothelin. This protein is present in advanced ovarian cancer. Although mesothelin is found in normal tissue, it’s found in abundance in ovarian cancer cells.

The current study found that infertile women, who are known to have an increased risk of ovarian cancer, were more likely to have the mesothelin antibody. The researchers also found that women with ovarian cancer were more likely to have this antibody.

“We’re taking a novel approach to try to identify earlier biomarkers of ovarian cancer by looking at high-risk women,” said study author Judith Luborsky, a professor of pharmacology, obstetrics and gynecology, and preventive medicine at Rush University Medical Center in Chicago.

“This study found that there are antibodies to mesothelin circulating in women that have infertility,” noted Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. Exactly what these findings mean isn’t yet clear, however. “Are these women who will develop ovarian cancer? Are these antibodies related to infertility? This research gives us some clues, and leads to many more questions,” he said.

As for an individual woman who’s currently concerned about ovarian cancer, Lichtenfeld said, “I would be very cautious about drawing any conclusion about the meaning of an elevated antibody level in an individual woman.”

Results of the study will be published Aug. 17 in the online version of the journal Cancer Epidemiology, Biomarkers & Prevention.

Almost 22,000 American women are diagnosed with ovarian cancer each year, and more than 15,000 women die each year as a result of this disease, reports the American Cancer Society.

Most women who develop ovarian cancer aren’t diagnosed until the disease is advanced. If it’s found early, ovarian cancer has a five-year survival rate of 94 percent, according to the cancer society. Two tests that experts hoped would help change that — a combination of transvaginal ultrasound and a blood test for CA-125, a marker associated with ovarian cancer — haven’t reduced a woman’s risk of dying from ovarian cancer, according to a recent study in the Journal of the American Medical Association.

Luborsky and her colleagues wanted to try to find a way to detect early cancer or a screening test for who’s at high risk for ovarian cancer before the cancer develops. Testing for mesothelin wouldn’t work, because it isn’t found at high levels until the cancer is advanced.

So, instead of looking for mesothelin, the researchers looked at a group of 109 infertile women, 28 women with ovarian cancer, and 24 women with benign ovarian cysts or tumors to see if these groups had antibodies to mesothelin. They also compared the three groups of women to healthy women to see if mesothelin antibodies were present.

Significant levels of mesothelin antibodies were found in women with ovarian cancer and in women with unexplained infertility or women who were infertile due to premature ovarian failure or ovulation problems. Women who were infertile due to endometriosis didn’t have significant levels of mesothelin antibodies, according to the study. Healthy women, and women with benign ovarian growths also didn’t have significant levels of mesothelin antibodies, the investigators found.

“There’s a lot more we have to learn, but our aim would be for a screening test that could improve detection,” said Luborsky.

Source: http://health.usnews.com/health-news/family-health/cancer/articles/2011/08/17/blood-antibody-may-signal-start-of-ovarian-cancer

Five Genes May Be Tied to Lethal Prostate Cancer

TUESDAY, Aug. 16 (HealthDay News) — In what may be a diagnostic advance, U.S. and Swedish researchers have linked five inherited genetic mutations to the development of a particularly aggressive and deadly form of prostate cancer.

Click here to find out more!

The findings could someday lead to development of an easy-to-administer blood test to screen for such mutations to help physicians assess the long-term risk faced by newly diagnosed prostate cancer patients, the researchers suggested.

“The ability to distinguish patients at elevated risk for having aggressive, life-threatening prostate cancer at the time of diagnosis could improve care for the subset of cases most likely to benefit from aggressive therapy and help avoid over-treatment of patients whose tumors are likely to remain indolent,” the study team, led by Janet L. Stanford, co-director of the Fred Hutchinson Cancer Research Center’s program in prostate cancer research, reported in the Aug. 16 online edition of Cancer Epidemiology, Biomarkers and Prevention.

At issue are longstanding concerns about unnecessary over-treatment of many prostate cancer patients who actually face a relatively low risk for fast disease progression and death. Because treatment can bring about undesirable side effects, such as sexual impotence and urinary incontinence, an effort has been under way to achieve a more personalized assessment of a patient’s particular prognosis after diagnosis.

“Biomarkers that could distinguish between patients with indolent vs. more aggressive tumors are urgently needed,” Stanford said in a journal news release. “The panel of markers we’ve identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. Ultimately these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, such as a high Gleason score, to identify men with a high-risk profile.”

The authors, looking for genetic differences that could highlight risk differences, gathered blood samples from more than 1,300 prostate cancer patients living in the Seattle region. All were between the ages of 35 and 74 when diagnosed.

DNA analyses of the samples were compiled with those of nearly 2,900 Swedish prostate cancer patients.

The result: Five single-letter mutations (or SNPs) were isolated among the patients’ “DNA alphabet” as having a significant bearing on prostate cancer progression in terms of affecting cell death, tumor growth, inflammation, androgen hormone levels, blood-vessel development and bone density.

Patients found to have at least four out of the five cited SNP mutations appeared to face a 50 percent higher risk for dying from their disease compared with those who carried two or fewer of the mutations.

William Phelps, program director of translational and preclinical cancer research at the American Cancer Society, said the push to develop more revealing diagnostic tools is driven by an acknowledgement that current treatment options can debilitate patients.

“If the treatments we had for prostate cancer were very tolerable or very safe you would probably treat everybody,” he explained. “But the treatments we have available today are less than ideal.”

“So certainly we can try to improve treatment,” Phelps noted. “But at the same time we can also try to improve ways to identify patients who are more likely to progress rapidly from those likely to be very slow going, so we can reserve treatment for only those instances when it’s really necessary.”

If there are markers that better define the men whose cancer is most likely to progress, “that would certainly prove very useful in the current climate,” he said.

Source: http://health.usnews.com/health-news/family-health/cancer/articles/2011/08/16/five-genes-may-be-tied-to-lethal-prostate-cancer

Suicide-Bombing Bacteria Could Fight Infections

Like any good military unit, infectious bacteria have access to numerous weapons and efficient communication systems. But like soldiers in the field, they’re also susceptible to suicide bombers. Researchers have used the tools of synthetic biology to create an Escherichia coli cell that can infiltrate foreign bacteria and explode, killing off the pathogens along with itself.

The project, says bioengineer Chueh Loo Poh of Nanyang Technological University in Singapore, was “inspired by nature,” particularly by quorum sensing, the ability of some bacteria to detect the number of microorganisms—either of their own species or others—in their environment. When pathogenic Pseudomonas aeruginosa sense other species impeding on their space and nutrients, they communicate with members of their own species using chemical signals and collectively start releasing a bacterial toxin called pyocin that kills off the competition. Together, these communication and defense capabilities allow P. aeruginosa to form tightly packed layers called biofilms, which can cause respiratory tract infections in humans and are particularly dangerous to cystic fibrosis patients.

Poh and chemical engineer Matthew Wook Chang, also at Nanyang Technological University, decided to turn P. aeruginosa‘s weapon system against itself, using E. coli as the carrier. The researchers tweaked the genes that allow P. aeruginosa to detect other members of its species and put this synthetic genetic code into E. coli‘s genome. They also gave E. coli a gene for making a modified pyocin that is toxic to P. aeruginosa. By linking the pyocin gene to the sensing genes, the researchers ensured that when the E. coli detected P. aeruginosa in the vicinity, it would fill itself with large amounts of pyocin and become a biological time bomb.

The researchers gave E. coli one last synthetic component: a “suicide gene” that is activated once the pyocin has had some time to build up, causing the cells to burst open and release their toxin. When Chang and Poh grew these synthetic E. coli in a dish with P. aeruginosa, the suicide bomber was able to kill 99% of the P. aeruginosa cells, the researchers report today in Molecular Systems Biology.

Justin Gallivan, a synthetic biologist at Emory University in Atlanta, says in an e-mail that the study “nicely illustrates” how synthetic bacteria can perform complex tasks. But he worries they may not be able to finish the job, because 1% of the infectious bacteria remained after the treatment—even when the researchers put four times as many E. coli as P. aeruginosa into the mix.

The system would also have to undergo a lot of work before it can be considered for use in humans—including, perhaps, replacing E. coli with another delivery system, says Richard Kitney, a synthetic biologist at Imperial College London. “Exposing people to E. coli is not a good thing,” Kitney says, as the bacteria are toxic outside the gut. He adds that the team would also have to show that pyocin is effective at killing P. aeruginosa that have already formed a biofilm.

For their part, Chang and Poh say that they plan to test the suicidal bacteria in mice infected with P. aeruginosa. It’s not clear, they say, whether pyocin is harmful to mammals, although some other natural bacterial toxins are currently approved for use as food preservatives. They also hope to tweak the synthetic system so that it can sense and respond to signaling molecules released by other species of pathogenic bacteria, such as those responsible for cholera.

Source: http://news.sciencemag.org/sciencenow/2011/08/suicide-bombing-bacteria-could-f.html

MS genetic discovery casts doubt on vein theory

Scientists have discovered 29 new genetic variations linked to multiple sclerosis, with many involving genes relevant to the immune system – a finding that they say bolsters the theory that MS is a primarily an autoimmune disease.

The new study, published Wednesday in the journal Nature, is the largest-ever study on the genetics of multiple sclerosis. More than 250 scientists collaborated on the work, and close to 10,000 MS patients were involved.

Many of the gene variations the team discovered are involved in the development of the immune system’s T-cells, which are the immune cells that protect against infections. When T-cells become “confused,” they trigger autoimmune diseases that mistake healthy body tissues as foreign and attack them.

The study authors say the findings reaffirm the long-held assertion that MS is primarily an autoimmune disorder and that changes in the immune system set off the disease.

“Our research settles a longstanding debate on what happens first in the complex sequence of events that leads to disability in multiple sclerosis,” Dr. Alastair Compston, a University of Cambridge neurology professor who was one of the leaders of the study, said in a statement.

“It is now clear that multiple sclerosis is primarily an immunological disease. This has important implications for future treatment strategies.”

The findings also cast doubt on the recent theory proposed by Italian vascular surgeon Dr. Paolo Zamboni that MS is related to blocked neck veins.

For this new study, researchers in Britain, Canada and a dozen other countries performed genome-wide scans on the DNA of 9,772 people with MS. They looked for genetic anomalies that didn’t appear in the DNA of 17,376 healthy people without MS.

They discovered the MS patients had 29 genetic variations that other patients didn’t have. They also confirmed 23 other genetic variations that had already been associated with MS. As well, the team identified five more associations that might be significant and that require further study.

One third of the genes identified have previously been implicated in playing a role in other autoimmune diseases such as Crohn’s Disease and Type 1 diabetes, indicating that the same processes occur in more than one type of autoimmune disease.

The findings cast doubt on the theory put forward by Dr. Zamboni. He suggests that blocked neck and chest veins stop blood from draining properly from the brain – a condition he calls CCSVI – which leads the blood to deposit iron in the brain. It’s the iron deposits that lead to the brain changes that mark MS, he contends.

To treat this, he proposes a vascular procedure to open blocked and twisted neck veins. Hundreds of Canadian patients have flown to overseas clinics for the so-called “libertion treatment,” spending upwards of $20,000 or more.

They’ve returned with various results. Some have reported the procedure helped relieve their fatigue; others said it allowed them to walk again, while still others say it offered no relief at all.

At least two patients have died after having the procedure, though it’s unclear what role it played in the deaths.

Zamboni has conducted studies that suggest that the majority of MS patients have CCSVI while few healthy patients so. But further studies have been unable to replicate his findings.

One study published this week in the Archives of Neurology found no significant difference in venous abnormalities between MS patients and healthy controls. But CCSVI proponents argue the studies were performed improperly.

The vein theory has not been embraced by many neurologists who specialize in MS. Many contend that patients have a genetic predisposition for MS and that one or more environmental factors trigger the condition.

Multiple sclerosis is marked by damage to nerve fibres in the brain and spinal cord and their protective insulation, called the myelin sheath. When the myelin is destroyed, it causes patients to struggle with everyday activities such as walking, feeling, thinking and controlling the bowel and bladder.

Even among those who believe MS is an autoimmune disease, it’s been unclear what sparks the immune changes. Previous research has suggested a vitamin D deficiency might be the trigger. Populations in northern hemispheres have higher rates of MS than populations with more year-round sunlight.

In this latest genetics study, researchers did identify two genetic variations that are involved in the metabolism of vitamin D.

Source: http://ottawa.ctv.ca/servlet/an/local/CTVNews/20110811/ms-gene-study-immune-system-110811/20110811/?hub=OttawaHome

New tests screen for gum disease, oral cancer

Future dental visits may involve more than a simple cleaning. Oral DNA testing may also help screen patients for gum disease or oral cancer.

Dr. Jessica Lawson of Urbandale Family Dentistry began offering the tests last spring. Two tests involve gum disease and a third for oral human papillomavirus, or HPV, assesses risks for oral cancer.

Researchers anticipate salivary testing may become the diagnostic tool of the future, in some instances even replacing blood work, said Lawson, one of the few dentists in the metro area offering the tests.

“It really supports what we’re doing with our patients. They know we have their best interest at heart. We’re looking to prevent, rather than treat and fix,” she said.

According to the manufacturer, OralDNA Labs, the periodontal tests have been available for nearly two years and the HPV test since January 2010.

Lawson’s staff educates all patients about testing, especially existing gum disease patients who don’t respond to frequent cleanings. Tests cost $150 each.

So far, 24 of her patients have undergone one of the gum disease tests. A handful had the HPV test, which can be a more difficult discussion since transmission is associated with sexual contact.

Testing is simple. Patients swish saline in their mouths for 30 seconds and spit it into a collection tube. The HPV test requires that patients gargle since the virus typically lives in the soft palate, esophagus and throat — similar to tissue in the cervix, where HPV is also present. Results are returned in seven to 10 days.

An estimated 50 to 60 percent of Americans have gum disease — some undiagnosed. Those patients usually have cleanings every three months. One test shows a patient’s genetic susceptibility to gum disease. It’s also a good test for new patients, Lawson said.

The other periodontal test shows what concentration of bacteria are present in the saliva and what antibiotic best treats it. The manufacturer recommends re-testing in six weeks.

Patient Amanda Rynning, 31, took that test a month ago to pinpoint the cause of tender, bleeding gums during flossing.

“I kind of questioned it a bit, but the more she talked about it and explained things, the more I felt comfortable taking the test,” she said.

The results allowed Lawson to customize Rynning’s antibiotic treatment and schedule a follow-up in a few weeks.

The test is also recommended for pregnant women to identify the presence of a specific oral bacteria associated with a higher rate of pre-term, low birth weight babies.

The HPV test targets two strains associated with squamous cell carcinoma of the head and neck, which affects 40,000 Americans every year.

As sexual activity is beginning at younger ages, the virus has become a hot topic, Lawson said.

“The prototype has changed for oral cancer. It used to be middle-aged to older men who were heavy tobacco users, abused alcohol and had other risk factors. Eighteen to 40-year-olds are now the high risk population for oral cancer due to increased sexual activity and skin-to-skin or mucous membrane transmission.”

Because there is no evidence Gardisil, an HPV vaccine, will protect against oral cancer, dentists may recommend exams every three months if needed. Lawson also can monitor with a VELscope, a fluorescent light that reflects light back at different wavelengths if tissue is damaged.

Caught early, the prognosis for oral cancer is good, Lawson said, adding that actor Michael Douglas was treated for the same condition. Initial symptoms include:

Earaches

Sore throat

Changes in voice box

Swollen, hard lymph nodes.

“We’re hoping with this test we’re monitoring things so at the first sign of symptoms we get them referred to the appropriate physicians,” she said.

Source: http://www.desmoinesregister.com/article/20110810/LIFE/308100026/-1/GALLERY_ARRAY/New-tests-screen-gum-disease-oral-cancer

Genetic mutations cause schizophrenia

More than 50 per cent of sporadic cases of schizophrenia are caused by new, or “de novo,” protein-altering mutations-genetic errors that are present in patients but not in their parents, a new research has shown.

A group led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhD, examined the genomes of patients with schizophrenia and their families, as well as healthy control groups. All were from the genetically isolated, European-descent Afrikaner population of South Africa.

They found 40 mutations, all from different genes and most of them protein-altering.

The results point the way to finding more, perhaps even hundreds, of mutations that contribute to the genetics of schizophrenia-a necessary step toward understanding how the disease develops, the researchers said.

“Identification of these damaging de novo mutations has fundamentally transformed our understanding of the genetic basis of schizophrenia,” says Bin Xu, PhD, assistant professor of clinical neurobiology at Columbia University Medical Center and first author of the study.

“The fact that the mutations are all from different genes,” says Karayiorgou, “is particularly fascinating. It suggests that many more mutations than we suspected may contribute to schizophrenia. This is probably because of the complexity of the neural circuits that are affected by the disease; many genes are needed for their development and function,” she added.

The study was recently published online in Nature Genetics.

Source: http://timesofindia.indiatimes.com/life-style/health-fitness/health/Genetic-mutations-cause-schizophrenia/articleshow/9527010.cms

Urine Test May Help Detect, Stratify Prostate Cancer

In men with elevated prostate specific antigen (PSA), an investigational urine test can detect and stratify prostate cancer, researchers reported.

The test is based on the detection of a gene fusion that is specific to prostate cancer, combined with another marker, according to Arul Chinnaiyan, MD, PhD, of the University of Michigan Medical School in Ann Arbor, and colleagues.

Stratifying patients by the combined marker identified groups with markedly different risks of cancer, high-grade cancer, and clinically significant cancer on biopsy, Chinnaiyan and colleagues reported online in Science Translational Medicine.

The noninvasive test could allow some men with elevated PSA to avoid a needle biopsy, the researchers noted.

“Many more men have elevated PSA than actually have cancer but it can be difficult to determine this without biopsy,” Chinnaiyan said in a statement. “The hope is that this test could be an intermediate step before getting a biopsy.”

The fusion at the heart of the test involves the genes transmembrane protease, serine 2 (TMPRSS2), and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG).

The fusion appears in about half of all prostate cancers, Chinnaiyan and colleagues noted, but when it appears it is almost 100% specific for malignancy.

In a series of experiments, the researchers showed that the fusion gene was associated with indicators of clinically significant cancer at biopsy and prostatectomy.

The indicators included tumor size, high Gleason score at prostatectomy, and upgrading of Gleason grade at prostatectomy, they reported.

But because the fusion gene is not universally present, the researchers created a model that combined it and the prostate cancer antigen 3 (PCA3) gene.

In 1,065 men who underwent biopsy, the researchers used the model to stratify men into three groups – lowest, intermediate, and highest levels of the combined genes.

They found that the groups had distinctly different patterns of risk. Specifically:

  • 363, 346, and 356 men were in the lowest, intermediate, and highest score groups, respectively – or 34%, 32% and 33%.
  • Biopsy resulted in a cancer diagnosis in 21%, 43%, and 69% of men in the lowest, intermediate, and highest groups, respectively. The difference between the low and high groups was significant at P<0.001.
  • 7%, 20%, and 40% of men in the lowest, intermediate, and highest groups were diagnosed with cancer that had a Gleason score of greater than 6. The difference between the low and high groups was again significant at P<0.001.
  • Of the 966 men with enough information to determine the Epstein criteria for significance of cancer on biopsy, 15%, 33%, and 61% of men in the three groups, respectively, had Epstein-criteria-defined significant cancer.

The researchers cautioned that the test remains investigational. As well, they noted, most of the men studied so far have been Caucasian, so that additional study is needed to see if the results apply more broadly.

Source: http://www.medpagetoday.com/HematologyOncology/ProstateCancer/27884?pfc=101&spc=224

Proteus Syndrom Gene Variant Identified

Researchers have discovered the gene mutation that leads to Proteus syndrome, a condition that causes different parts of the body to grow faster and larger than others, HealthDay reports.

With only about 500 cases known in the developed world, Proteus syndrome is rare. The condition is marked by a partial enlargement of the hands or feet, an enlarged head and overgrowth of one side of the face, body or limbs. It is thought to be the cause of the disabilities of 19th century Englishman Joseph Merrick, popularly known as the “Elephant Man.”

According to HealthDay, Proteus syndrome is a mosaic disorder, one in which some cells in the body have the genetic mutation and some don’t. Working on identifying the specific gene variant since 1996, researchers at the U.S. National Human Genome Research Institute were finally able to compare tissue samples from affected areas of the body to unaffected areas in 29 Proteus syndrome patients. They were able to identify the same mutation in 26 patients.

The mutation occurred in the AKT1 gene, they said. HealthDay explains the mutation as “a single ‘misspelling’ in the billions of letters that make up the human genome.”

HealthDay noted that the gene mutation in Proteus syndrome creates an oncogene, which drives the uncontrolled cell division. Oncogenes are usually associated with cancer, the website reported.

Researchers hope that finding the gene will be able to lead to better treatment for people with Proteus syndrome.

“It may become possible to treat those with Proteus syndrome with a drug originally developed for cancer,” said the study’s senior author Leslie Biesecker. “This allows us to leapfrog a number of steps. But, Proteus syndrome is not an overgrowth syndrome so we would have to adapt cancer treatments.”

Source: http://www.thirdage.com/news/proteus-syndrom-gene-variant-identified_07-28-2011

Studies Show Natural Protein May Provide Benefits Against Stroke up to 12 Hours After Onset

    Scientists suggest that treating stoke patients with an endogenous immunomodulatory neuroprotectant protein, ?B-crystallin (Cryab), could help limit brain damage even if first administered 12 hours after the onset of stroke. Studies by a Stanford University School of Medicine team in a mouse model of stroke found that administering Cryab to animals 12 hours after stroke induction led to significantly reduced stroke volume and lower levels of inflammatory cytokines associated with stroke pathology than untreated mice.

    Conversely, animals in which the Cryab gene had been knocked out demonstrated increased lesion size and diminished neurologic function after stroke than wild-type mice. The research team, led by Gary K. Steinberg, M.D., director of Stanford’s Institute for Neuro-Innovation and Translational Neurosciences, reports its findings in PNAS in a paper titled “Systemic augmentation of ?B-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation.”

    Tissue plasminogen activator (tPA) is currently the only FDA-approved treatment for stroke, and must be given within 4.5 hours of stroke onset to be effective, the researchers note. tPA acts through the conversion of plasminogen into active plasmin, to cleave the blood clot, and exemplifies strategies that aim to alter the obstructive blood clot rather than actually protect the damaged brain.

    Cryab, meanwhile, is a small heat shock protein (designated sHSP B5) that is constitutively expressed in the lens of the eye and muscle, and is induced in many types of brain injury. Previous studies have shown the protein has both anti-apoptotic and immunomodulatory properties; it is also the most abundant induced transcript in multiple sclerosis lesions and is highly expressed in areas of inflammation, the authors add.

    Previous studies by a group led by co-author Lawrence Steinman, M.D., George A. Zimmermann professor of neurology and neurological sciences and pediatrics at Stanford, had found that Cryab reduces the severity of brain damage caused by multiple sclerosis, and that the protein can also limit the damage caused by reduced blood supply to heart tissue and to the retina. These findings, coupled with other research suggesting that Cryab has neuroprotective properties, led Drs. Steinberg, Steinman, and colleagues to evaluate the effects of Cryab deficiency on cerebral ischemia.

    They found that Cryab-knockout animals demonstrated significantly larger lesions two days after an induced cerebral artery occlusion than wild-type mice. This increased damage in the Cryab-deficient animals persisted at seven days, indicating that Cryab deficiency affects both the early and delayed phases of ischemic damage. The Cryab-knockout mice also scored significantly worse in terms of functional assessment.

    Interestingly, granulocyte and macrophage populations, and the subpopulation of monocytes, were significantly higher in the Cryab-deficient mice at the two-day post-stroke stage, but not at seven days. The numbers of lymphoid cells, however, were significantly increased in the knockout animals at seven days. More specifically, there were increased numbers of granulocytes and activated macrophages in the Cryab-deficient mice than in the wild-type controls at two days. There were also marked increases in the numbers of T cells in the brains of Cryab knockouts than wild-type mice at seven days and, in particular, increased levels of IL-17-producing ??-TCR+ (??-T) cells. The overall data suggested that “a deficiency of Cryab might lead to a more vigorous inflammatory response to stroke,” the authors note.

    Because some research has previously suggested that Cryab expression is upregulated in neurons and astrocytes after cerebral ischemia, the researchers moved on to analyze levels of Cryab in the plasma of wild-type mice before stroke, and at various time points after the induction of stroke. This showed that Cryab levels were significantly increased at the 12 hour time point, and decreased gradually over the next seven days.

    When they analyzed the plasma concentrations of Cryab in human patients with ischemic stroke, they found increased levels of the protein in younger patients within four hours of stroke symptom onset, but surprisingly not in older patients. In younger patients only, lesion volume also correlated with plasma Cryab levels, “perhaps indicating that the body’s endogenous response to stroke is age dependent,” the team suggests.

    To test the notion that increased plasma Cryab after stroke is beneficial, Cryab-knockout mice were given intraperitoneal injections of recombinant Cryab protein, starting one hour before stroke onset and continuing at 12 hours, 24 hours, and then daily for seven days in total. Lesion sizes in the Cryab-treated knockout mice were significantly smaller than those of the knockout animals that weren’t given exogenous Cryab. Evaluation of splenocytes from PBS-treated wild-type mice, Cryab-deficient animals, and Cryab-treated Cryab-knockout animals showed that those of PBS-treated knockouts produced more proinflammatory IL-2, IL-17, and TNF than both PBS-treated wild-type mice and Cryab-treated Cryab-deficient mice. The animals receiving exogenous Cryab also produced more anti-inflammatory IL-10. “These data indicate that restoration of plasma Cryab by systemic treatment modulates the peripheral inflammatory response and is sufficient to decrease the lesion sizes in Cryab?/? mice to the levels of wild-type mice after stroke,” the researchers note.

    They progressed to evaluate whether Cryab therapy could benefit wild-type mice after stroke onset. When Cryab was administered one hour before and 12 hours after stroke onset, the lesion size at two days was not different between PBS- and Cryab-treated wild-type mice groups. In contrast, when it was administered 1 hour before, 12 hours and 24 hours after, and then daily for seven days, the lesion sizes were significantly reduced in the Cryab-treated group compared with the PBS-treated group. “Moreover, starting the initial treatment even 12 hours after the stroke onset—making the treatment highly relevant if translated into the clinic—conferred neuroprotection in the Cryab-treated group,” the team claims. Analysis of splenocytes cytokines seven days after stroke in wild-type mice again showed that the Cryab-treated animals produced less proinflammatory IL-2, IL-17, IFN-?, IL-12p40, and IL-6, and more anti-inflammatory IL-10, than the PBS-treated animals.

    “Our findings describe a therapeutic role for Cryab in stroke, and emphasize how it functions as an endogenous neuroprotectant by modulating the immune system,” the authors conclude. “Its presence as an endogenous protectant can be exploited by administering it in larger quantities as a therapeutic agent. Its benefit seen with starting the treatment 12 hours after stroke would represent a significant improvement over tPA if translated to the clinic.”

    Source: http://genengnews.com/gen-news-highlights/studies-show-natural-protein-may-provide-benefits-against-stroke-up-to-12-hours-after-onset/81245471/

Smelly socks tested in Tanzania as way to prevent malaria

In global public health, disease-fighting tools that are cheap, available and sustainable are the Holy Grail. It might be hard to top the one being tested in Tanzania as a way to prevent malaria: smelly socks.

Experiments in three villages where people get about 350 bites a year from malaria-infected mosquitoes are using dirty socks to lure the insects into traps, where they become contaminated with poisons and ultimately die.

Researchers hope that if the strategy works, it will eventually complement insecticide-treated bed nets as a low-tech way to prevent malaria, which kills nearly 900,000 people a year worldwide, most of them children.

“It’s a bold idea. Who would have thought there was a life-saving technology working in your laundry basket?” said Peter A. Singer, a physician who heads Grand Challenges Canada, a development agency of the Canadian government that is helping fund the research.

Previous lab studies have shown that smelly socks work well in attracting mosquitoes. Field experiments have shown that synthetic bait is more attractive than people, at least until the insects get close enough to realize there’s no blood waiting for them.

The new experiments, however, are the first head-to-head field tests of footwear vs. chemistry. The researchers hope the footwear wins.

“It is simply a cost issue and an expediency issue,” said Fredros O. Okumu, the Tanzanian entomologist leading the research. “Socks are more readily available, and you don’t have to mix any chemicals. It is the sort of thing that could be set up in a cottage factory.”

The traps are square boxes that look a little like commercial beehives. Some will contain the human-odor bait, which consists of simple chemicals (including lactic acid, ammonia and propionic acid) that are exuded by people, especially from the legs and feet. Some will contain socks worn for a day by adults. Others will contain cotton pads that schoolchildren will put inside their socks for a day and then deliver to researchers.

The researchers will compare the number of mosquitoes caught with each method.

Earlier work by Okumu and his colleagues at the Ifakara Health Institute in Tanzania showed that the chemical bait attracted four times as many mosquitoes as live people and that dirty socks worked just as well, at least in the lab. If the sock pads prove adequate, they will be the preferred bait.

The inside surfaces of some traps are coated with an organophosphate pesticide. Mosquitoes that land there will die within 24 hours. Other traps contain a fungus that infects the insects and kills them in five days — roughly half the time needed for the complicated cycle that enables a newly infected mosquito to transmit the malaria parasite to a person.

The bait-and-kill strategy is a new one in malaria prevention efforts.

Normally, attempts to prevent malaria by controlling mosquitoes, known as vector control, have aimed at driving the insects away from people or killing them once natural attraction has brought them into proximity.

Insecticide-treated bed nets, millions of which have been sold or given away in Africa in the past decade, have a long-acting repellant, permethrin. In many malaria-endemic areas, people spray the inside walls of dwellings with insecticide that kills mosquitoes when they land.

Bed nets have cut childhood deaths by about 20 percent in malaria-endemic areas. Modeling suggests that traps could reduce malaria transmission about as much as bed nets do in villages where half the households use them.

Despite its low-tech appearance, the strategy Okumu is testing is far more complicated, and potentially fraught with hazard, than it seems.

A key question is where to place traps. They need to be close enough to dwellings to attract mosquitoes, but not so close that they will increase people’s exposure to the disease-carrying insects. Okumu’s research suggests that the traps should be at least 100 feet from houses.

Another question is how many traps a village might need. Okumu has calculated the minimum number at 20 per 1,000 people, although in places where malaria transmission is especially intense and in certain village configurations, 130 traps per 1,000 people might be needed.

Despite these challenges, Singer said, projects such as these are what Grand Challenges Canada is looking to support. It is providing $388,000 for the research, and the Bill and Melinda Gates Foundation is providing a similar amount. The Gates Foundation gave Okumu $100,000 for preliminary studies, as well.

“We are inspired by people like Fredros,” Singer said. “We strongly believe that innovators in low-income countries are best situated to solve their own problems. He is an African researcher with an African innovation for an African problem.”

Okumu, who is a doctoral candidate at the London School of Hygiene and Tropical Medicine, said he is “working on the premise that this is a global problem — a global problem in a flat world.”

He said he doubted that there might be an application for his strategy — should it prove successful — in non-malarious places such as the United States. A pair of socks from a recent 10K run at the corner of a patio will only briefly divert mosquitoes. They’ll soon find the bare legs under the picnic table.

“Mosquitoes are still fairly clever animals,” he said. “What they are looking for is blood. They might be attracted to the socks, but they will not spend much time there.”

Source: http://www.washingtonpost.com/national/health-science/smelly-socks-tested-in-tanzania-as-way-to-prevent-malaria/2011/07/12/gIQAshifBI_story.html

Scientists Discover Gonorrhea Resistant to Antibiotics

(EndPlay Staff Reports) – A new untreatable strain of gonorrhea has been discovered in Japan and is causing concern in the United States.

Scientists reported that the strain, which is named H041, is resistant to all known forms of antibiotics. The researchers discussed the findings at a Monday meeting in Canada about three days after the CDC warned on July 8 that gonorrhea samples in the U.S. are also showing signs of drug resistance.

The concern is that the new strain of Neisseria gonorrhoeae is resistant to the cephalosporin family of antibiotics such as ceftriaxone, cefixime and cefpodoxime, which are widely used to treat the sexually transmitted disease in the United States. The CDC warned that this is a concern because it only leaves a few antibiotic options that are “simple, well-studied, and highly effective.”

The resistance to antibiotics, according to the CDC , was first documented in Asia before emerging in Hawaii and other western states then spreading elsewhere.

“This is a large public health problem and the era of untreatable gonorrhea may now have been initiated,” the team of researchers said at the Quebec City meeting of the International Society for Sexually Transmitted Disease Research, The Los Angeles Times reported.

The US Gonococcal Isolate Surveillance Project launched in 1986 has not discovered any U.S. cases in which treatment with cephalosporin antibiotics was a complete failure. The Times, though, reported there have been more cases that required unusually high doses of the antibiotic to cure them.

The majority of samples showing this trend were obtained from men having sex with men, the newspaper stated. The largest growth in cases noticed between 2000 and 2010 have been in Hawaii and California.

As a precaution, the CDC is suggesting dual treatment with another antibiotic such as azithromycin or doxycycline.

Gonorrhea, ABC News reported, is one of the most common STDs with about 700,000 new cases each year in the United States. It is spread through direct contact with the penis, vagina, mouth or anus and can also be transmitted from mother to baby during birth.

Only about half of infected women and less than five percent of infected men develop symptoms including a burning sensation and discharge. ABC News said it can spread to the skin, blood and other organs and cause pain, infertility and death if not treated.

Scientists are concerned that such a strain could spread quickly if new ways are not found to stop it. Dr. William Schaffner, chair of preventive medicine at Vanderbilt University Medical Center in Nashville, Tenn., told ABC News that this coincides with cutbacks in research as pharmaceutical companies invest less in the search for new antibiotics.

While the strain that did not respond at all to antibiotics was discovered in Kyoto, Japan, he warned, such bacteria “don’t need a passport” to spread.

Source: http://www.myfoxboston.com/dpps/health/scientists-discover-gonorrhea-resistant-to-antibiotics-dpgoha-20110712-fc_14088790

Who wants to live forever? Scientist sees aging cured

(Reuters) – If Aubrey de Grey’s predictions are right, the first person who will live to see their 150th birthday has already been born. And the first person to live for 1,000 years could be less than 20 years younger.

A biomedical gerontologist and chief scientist of a foundation dedicated to longevity research, de Grey reckons that within his own lifetime doctors could have all the tools they need to “cure” aging — banishing diseases that come with it and extending life indefinitely.

“I’d say we have a 50/50 chance of bringing aging under what I’d call a decisive level of medical control within the next 25 years or so,” de Grey said in an interview before delivering a lecture at Britain’s Royal Institution academy of science.

“And what I mean by decisive is the same sort of medical control that we have over most infectious diseases today.”

De Grey sees a time when people will go to their doctors for regular “maintenance,” which by then will include gene therapies, stem cell therapies, immune stimulation and a range of other advanced medical techniques to keep them in good shape.

De Grey lives near Cambridge University where he won his doctorate in 2000 and is chief scientific officer of the non-profit California-based SENS (Strategies for Engineered Negligible Senescence) Foundation, which he co-founded in 2009.

He describes aging as the lifelong accumulation of various types of molecular and cellular damage throughout the body.

“The idea is to engage in what you might call preventative geriatrics, where you go in to periodically repair that molecular and cellular damage before it gets to the level of abundance that is pathogenic,” he explained.

CHALLENGE

Exactly how far and how fast life expectancy will increase in the future is a subject of some debate, but the trend is clear. An average of three months is being added to life expectancy every year at the moment and experts estimate there could be a million centenarians across the world by 2030.

To date, the world’s longest-living person on record lived to 122 and in Japan alone there were more than 44,000 centenarians in 2010.

Some researchers say, however, that the trend toward longer lifespan may falter due to an epidemic of obesity now spilling over from rich nations into the developing world.

De Grey’s ideas may seem far-fetched, but $20,000 offered in 2005 by the Massachusetts Institute of Technology (MIT) Technology Review journal for any molecular biologist who showed that de Grey’s SENS theory was “so wrong that it was unworthy of learned debate” was never won.

The judges on that panel were prompted into action by an angry put-down of de Grey from a group of nine leading scientists who dismissed his work as “pseudo science.”

They concluded that this label was not fair, arguing instead that SENS “exists in a middle ground of yet-to-be-tested ideas that some people may find intriguing but which others are free to doubt.”

CELL THERAPY

For some, the prospect of living for hundreds of years is not particularly attractive, either, as it conjures up an image of generations of sick, weak old people and societies increasingly less able to cope.

But de Grey says that’s not what he’s working for. Keeping the killer diseases of old age at bay is the primary focus.

“This is absolutely not a matter of keeping people alive in a bad state of health,” he told Reuters. “This is about preventing people from getting sick as a result of old age. The particular therapies that we are working on will only deliver long life as a side effect of delivering better health.”

De Grey divides the damage caused by aging into seven main categories for which repair techniques need to be developed if his prediction for continual maintenance is to come true.

He notes that while for some categories, the science is still in its earliest stages, there are others where it’s already almost there.

“Stem cell therapy is a big part of this. It’s designed to reverse one type of damage, namely the loss of cells when cells die and are not automatically replaced, and it’s already in clinical trials (in humans),” he said.

Stem cell therapies are currently being trialed in people with spinal cord injuries, and de Grey and others say they may one day be used to find ways to repair disease-damaged brains and hearts.

NO AGE LIMIT

Cardiovascular diseases are the world’s biggest age-related killers and de Grey says there is a long way to go on these though researchers have figured out the path to follow.

Heart diseases that cause heart failure, heart attacks and strokes are brought about by the accumulation of certain types of what de Grey calls “molecular garbage” — byproducts of the body’s metabolic processes — which our bodies are not able to break down or excrete.

“The garbage accumulates inside the cell, and eventually it gets in the way of the cell’s workings,” he said.

De Grey is working with colleagues in the United States to identify enzymes in other species that can break down the garbage and clean out the cells — and the aim then is to devise genetic therapies to give this capability to humans.

“If we could do that in the case of certain modified forms of cholesterol which accumulate in cells of the artery wall, then we simply would not get cardiovascular disease,” he said.

De Grey is reluctant to make firm predictions about how long people will be able to live in future, but he does say that with each major advance in longevity, scientists will buy more time to make yet more scientific progress.

In his view, this means that the first person who will live to 1,000 is likely to be born less than 20 years after the first person to reach 150.

“I call it longevity escape velocity — where we have a sufficiently comprehensive panel of therapies to enable us to push back the ill health of old age faster than time is passing. And that way, we buy ourselves enough time to develop more therapies further as time goes on,” he said.

“What we can actually predict in terms of how long people will live is absolutely nothing, because it will be determined by the risk of death from other causes like accidents,” he said.

“But there really shouldn’t be any limit imposed by how long ago you were born. The whole point of maintenance is that it works indefinitely.”

Source: http://www.reuters.com/article/2011/07/04/us-ageing-cure-idUSTRE7632ID20110704

Hemophilia Is Target of Therapy on Genome

Researchers using a new technique for editing the genome of living cells have shown that they can cure hemophilia in mice, at least in principle, with a couple of injections that carry out the “cut” and “paste” operations needed to insert a corrective gene.

This is the first time this genome-editing technique has succeeded in a live animal. Along with other applications, like two AIDS treatments in preliminary stages, the new technique could be the decisive improvement that gives credibility to the long-struggling field of gene therapy.

“This may well revolutionize the field, but it won’t do so overnight,” said Dr. Katherine A. High of the Children’s Hospital of Philadelphia, the research team leader. “Any novel kind of therapeutic takes time to develop.”

The essence of the technique is the molecular scissors custom-designed to cut the genome at a unique site. This allows the corrective gene to be inserted at the right place in a chromosome.

In previous forms of gene therapy, corrective genes have been inserted into the genome at random sites, for lack of the ability to control where they go. This approach means they are not under their natural control systems and, worse, may be inserted in the middle of some other gene that they disrupt.

“There’s a huge interest in this,” said Dr. Mark A. Kay, a gene therapist at the Stanford University School of Medicine. The genome editing approach “could be game-changing in some applications,” he said.

The technique depends on natural agents called zinc finger proteins whose role is to bind to specific sites on the genome and control adjacent genes. By mixing and matching the DNA of different natural zinc finger proteins, researchers can create artificial zinc fingers for any chosen target site on the genome.

In their genome-editing role, the zinc fingers are attached to a DNA-cutting enzyme derived from a bacterium. When a pair of zinc finger proteins line up on opposing strands of DNA, their DNA cutters face each other and scissor the DNA apart.

The zinc finger technique has been developed by Sangamo BioSciences and by academic researchers who belong to the Zinc Finger Consortium. “We are fairly inundated with requests,” said Philip D. Gregory, Sangamo’s chief scientific officer.

Sangamo designed the zinc finger pairs for Dr. High’s hemophilia project. But the fingers are designed to cut the human Factor 9 gene, not the mouse version, which has a different sequence of DNA units. So Dr. High genetically engineered a strain of hemophiliac mice that carry a mutated version of the human Factor 9 gene in place of their own.

After the cut-and-paste operation, the mice possessed a good working copy of human Factor 9, producing enough to make their blood clot much faster, and well enough to prevent hemophilia, Dr. High and her colleagues report in the journal Nature. To show that the new gene was stably incorporated into cells, they then cut out part of the mice’s livers. The liver regenerated from existing cells, retaining their ability to produce good copies of Factor 9.

Dr. High said it was too soon to try the technique in people, given that an adequate treatment for hemophilia already exists. She plans to test it next in dogs, which are a standard model for new hemophilia treatments. One of the possible problems with the technique is that the zinc fingers sometimes cut at sites other than the intended target site.

Dr. High said that besides hemophilia, the zinc finger technique could address many other liver-based genetic diseases.

Zinc fingers are being used in a different way in a treatment for AIDS, at present in early clinical trials. The fingers are used to disrupt a gene called CCR5, which makes the receptor used by the AIDS virus to gain access to cells. People with no CCR5 receptor are naturally immune to AIDS.

The hope is that patients will acquire the same immunity after their T cells are treated with zinc fingers and returned to the body.

“We are very hopeful that zinc finger technologies will have a spectacular impact on gene therapy and genetic medicine in general,” Dr. Gregory said.

Source: http://www.nytimes.com/2011/06/27/us/27therapy.html