Archive for the ‘Discoveries, Innovations and Patents’ Category

New tests screen for gum disease, oral cancer

Last Updated on Wednesday, 10 August 2011 11:10 Written by admin Wednesday, 10 August 2011 11:10

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

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Genetic mutations cause schizophrenia

Last Updated on Monday, 8 August 2011 11:28 Written by admin Monday, 8 August 2011 11:28

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

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Urine Test May Help Detect, Stratify Prostate Cancer

Last Updated on Thursday, 4 August 2011 11:07 Written by admin Thursday, 4 August 2011 11:07

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

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Scientists Claim Leukemia Stem Cell Signature Independently Predicts Poor Survival in AML

Last Updated on Friday, 2 September 2011 11:39 Written by admin Tuesday, 2 August 2011 11:27

Research on samples from human acute myeloid leukemia (AML) patients has suggested that the a leukemia stem cell (LSC) gene expression profile can accurately be used to predict patient survival, even among AML patients with cytogenetically normal disease. An international team led by researchers at Ontario’s University Health Network and the University of Toronto’s Department of Molecular Genetics claim their findings support those from xenograft models suggesting that the disease is propagated by a population of rare LSCs.

Describing their findings in Nature Medicine, John E. Dick, M.D., Kolja Eppert, M.D., and colleagues report that the LSC gene signature is similar to that of hematopoietic stem cells (HSCs), and that both gene signatures were significant and independent predictors of patient survival. Moreover, the LSC gene signature could accurately predict poor survival in about 50% of AML patients with cytogenetically normal disease who would otherwise be classified as low risk on the basis of mutations in specific individual genes. Importantly, the LSC signature could be identified even in unsorted AML cell populations in which LSCs were very rare, suggesting that LSC-derived AML-blasts retain at least part of their progenitors’ expression profiles.

The researchers finally highlight the need to develop LSC biomarkers for use in patient evaluation, and claim that therapies targeting LSCs would improve survival outcomes. Their paper is titled “Stem cell gene expression programs influence clinical outcome in human leukemia.”

Xenograft studies indicate that some solid tumors and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSCs), the authors write. Although the clinical relevance of the CSC model in humans has, to date, remained uncertain, recent evidence from leukemia patients does support the notion that LSC properties may be prognostic: correlative studies have linked outcome with either the capacity for a sample to be xenografted or surface expression of LSC-linked markers.

Moreover, they continue, if CSCs are more prognostic than non-CSCs, the molecular machinery underpinning the properties of such stem cells is likely to likely to influence clinical outcome. “Indeed, LSCs have the core set of biological functions common to all stem cells, including self-renewal and the ability to produce differentiated, non-stem cell progeny.”

The University Health Network team set out to investigate the specific properties of CSCs in leukemia further by defining the gene expression signatures of both LSCs and hematopoietic stem cells (HSCs) from functionally validated, sorted fractions of primary human AML samples. Sixteen primary human AML samples were sorted into four cell populations on the basis of surface expression of the markers CD34 and CD38: previous studies have suggested LSCs are primarily CD34⁺CD38^-. Each cell fraction was then assayed using an optimized xenotransplantation assay to identify LSC-enriched and LSC-depleted populations.

As expected, LSCs were found in the CD34⁺CD38^? fraction in all but one of the informative cases. However, the cells were also found in at least one other fraction in the majority of AML samples, and in 50% of cases the majority of LSCs were found in the CD34⁺CD38⁺ fraction, “establishing heterogeneity between cell surface marker expression and LSC activity among individual samples,” the authors state. Overall, LSCs ranged in frequency from 1 in 1.6 × 10³ cells, to 1 in 1.1 × 10⁶, but were generally found at the highest frequency in the CD34⁺CD38^? fraction. Importantly, the researchers note, “LSC-containing fractions that initiated leukemia generated a xenograft that acquired the marker phenotype of non-LSC fractions, confirming earlier reports that AML is hierarchically organized.”

Each functionally validated fraction was then subjected to global gene expression analysis to identify LSC-related (LSC-R) gene profiles. Bioinformatics analyses compared global gene expression patterns of 25 LSC-enriched fractions to 29 fractions without LSCs. The results threw up an initial LSC-R signature including 42 genes, which was validated by RT-PCR. This same gene signature was identified in AML samples with a variety of karyotypic alterations and French-American-British subtype.

Then, because LSCs and HSCs both have canonical stem cell functions including self-renewal and the ability to make non-stem cell, mature progeny, the team also generated HSC gene-expression profiles to see whether human LSCs share molecular mechanisms and gene-expression programs with HSCs.

A comparison of the resulting 121-gene HSC-related (HSC-R) profile with the LSC-R gene profile identified 44 leading-edge genes, termed the core enriched HSC-LSC genes (CE-HSC-LSC), which appeared to represent HSC genes that are also differentially expressed in LSCs. Of these, 18 are implicated in stem cell regulation, oncogenesis, or both, the authors note. However, protein interaction network analyses highlighted the enrichment of multiple pathways distinct from the progenitor network, including Notch and Jak-STAT signaling, which are implicated in stem cell regulation, “thereby supporting the stem cell nature of the HSC- and LSC-related gene profiles.”

Significantly, when the researchers compared their data with previously generated gene datasets from stem, progenitor, and mature cell populations, and from embryonic stem cells, they found that LSC gene expression correlated positively with primitive cell gene sets and negatively with gene sets derived from more differentiated cells and from ES cells. “Collectively, our data establishes that an HSC expression program and not a common lineage-committed progenitor or ES cell-expression pattern is preferentially expressed in LSCs compared with more mature non-LSC leukemic cells,” they conclude.

To test the clinical relevance of LSCs, the team then looked for a link between LSC-R and HSC-R gene signatures and clinical outcomes, in three large clinically annotated gene expression datasets derived from unsorted AML cells. They found that the LSC-R and HSC-R profiles were very similar among a cohort of 285 AML samples, and that the profiles were either positively or negatively correlated with cluster gene sets characterized by molecular markers indicative of poor prognosis or good prognosis.

They then analyzed the LSC-R, HSC-R, and CE-HSC-LSC signatures in new gene expression data generated on about a third of the AML samples that had been stratified in terms of poor or good prognostic risk groups on the basis of cytogenetic alterations. In this case higher expression of all three signatures distinguished poor prognostic risk subjects. “These findings demonstrate that AML samples associated with worse prognosis express stem cell-related genes more highly than less aggressive AML samples,” they note.

As a final test of clinical relevance, the researchers looked at a cohort of 160 cytogenetically normal AML subjects for whom gene expression and survival data were available. For this analysis they used the LSC-R or HSC-R gene signature to divide the subjects into two equal groups, based on the median expression of the respective signatures in bulk AML bone marrow cells.

Both signatures negatively correlated with overall survival and event-free survival with a high degree of significance. Moreover, there was a significant negative correlation between the occurrence of complete remission and high expression of the LSC-R signature, and an almost significant negative correlation between complete remission occurrence and the HSC-R signature. “Our data demonstrate that high expression of stem cell expression signatures directly predicts patient survival in cytogenetically normal AML and, therefore, that variation in stem cell expression programs among subject samples is highly correlated with heterogeneity in disease outcome,” the team writes.

Of particular interest, multivariate analyses showed that the LSC-R and HSC-R signatures predicted overall and event-free survival independently of known molecular prognostic factors in cytogenetically normal patients, such as molecular risk status and CEBPA mutation. In fact, after subdividing the AML samples that were informative for molecular risk status, they found that each stem cell signature identified subsets of subjects with poor survival in both high molecular risk (HMR) group and low molecular risk (LMR) groups. “Thus, the LSC-R and HSC-R signatures can be used to separate patients currently identified as low risk into groups who respond well to standard therapy and those who may benefit from more intensive therapy, including stem cell transplant.”

The researchers state their studies provide evidence supporting the hierarchical organization of AML according to the CSC model, and support the notion that LSCs are not just artifacts of experimental xenograft models. Moreover, they suggest a similar investigative approach could be used to assess both the identity and clinical relevance of LSCs and CSCs from other leukemias and solid tumors.

“Our findings warrant validation in a large cohort and a clinical trial to test the LSC-R signature in the LMR subgroup,” they continue. “If our results are confirmed, poor-risk patients might benefit from more aggressive therapy such as allogeneic transplant or alternative therapy.”

The authors admit that they found it rather counterintuitive that a stem cell signature could be detected in unsorted samples containing a very small population of LSCs, and in which the vast majority of cells are differentiated non-LSC blasts. This, they remark, suggests that stem cell expression programs persist in these blasts at a population level, even though no individual blast retains the full repertoire or expression level of stem cell genes.

Source: http://genengnews.com/gen-news-highlights/scientists-claim-leukemia-stem-cell-signature-independently-predicts-poor-survival-in-aml/81245599/

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Women who eat lots of fiber have less breast cancer

Last Updated on Friday, 29 July 2011 11:35 Written by admin Friday, 29 July 2011 11:35

(Reuters Health) – A fresh look at the medical evidence shows women who eat more fiber are less likely to get breast cancer.

Chinese researchers found those who ate the most of the healthy plant components were 11 percent less likely to develop breast cancer than women who ate the least.

Their findings don’t prove fiber itself lowers cancer risk, however, because women who consume a lot of it might be healthier overall than those who don’t.

The results “can identify associations but cannot tell us what will happen if people change their behavior,” said John Pierce, a cancer research at the University of California, San Diego, who was not involved in the work.

While earlier research has yielded mixed conclusions on the link between cancer and fiber, it would make scientific sense: According to the Chinese researchers, people who eat high-fiber diets have lower levels of estrogen, which is a risk factor for breast tumors.

So to get more clarity, the researchers combined 10 earlier studies that looked at women’s diets and followed them over seven to 18 years to see who developed cancer.

Of more than 710,000 women, 2.4 percent ended up with breast cancer. And those in the top fifth of fiber intake were 11 percent less likely to do so than women in the bottom fifth.

That was after accounting for differences in risk factors like alcohol drinking, weight, hormone replacement therapy and family members with the disease.

Still, it’s impossible to rule out that big fiber eaters had healthier habits overall that would cut their risk, Jia-Yi Dong of Soochow University in Suzhou and his colleagues write in the American Journal of Clinical Nutrition.

And the potential effect was “very small,” Dr. Eleni Linos of Stanford University, who wasn’t involved in the research, told Reuters Health in an email.

About one in eight American women get breast cancer at some point, with less than a quarter of them dying from it.

Although the connection between breast cancer risk and fiber is a small one, fiber is “something that we know is healthy for you anyway,” said Christina Clarke, a research scientist at the Cancer Prevention Institute of California in Fremont.

Known benefits of a high-fiber diet include lower cholesterol and weight loss. If it turns out to cut cancer risk as well, that would be an extra bonus, Clarke said.

Fruits, vegetables, beans, and whole grains are all high in fiber.

According to the U.S. Department of Agriculture’s 2010 Dietary Guidelines, most Americans don’t get enough fiber. The guidelines recommend that women eat 25 grams of fiber per day and men eat 38 grams, while the average Americans gets just 15 grams a day.

“Increasing dietary fiber intake in the general public is of great public health significance,” the Chinese team concludes.

Source: http://www.reuters.com/article/2011/07/28/us-fiber-breast-cancer-idUSTRE76R6YM20110728

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‘Super antibody’ fights off flu

Last Updated on Friday, 29 July 2011 11:22 Written by admin Friday, 29 July 2011 11:22

The first antibody which can fight all types of the influenza A virus has been discovered, researchers claim.

Experiments on flu-infected mice, published in Science Express, showed the antibody could be used as an “emergency treatment”.

It is hoped the development will lead to a “universal vaccine” – currently a new jab has to be made for each winter as viruses change.

Virologists described the finding as a “good step forward”.

Many research groups around the world are trying to develop a universal vaccine. They need to attack something common to all influenza which does not change or mutate.

Human source

It has already been suggested that some people who had swine flu may develop ‘super immunity’ to other infections.

Scientists from the Medical Research Council’s National Institute for Medical Research at Mill Hill and colleagues in Switzerland looked at more than 100,000 samples of immune cells from patients who had flu or a flu vaccine.

They isolated an antibody – called FI6 – which targeted a protein found on the surface of all influenza A viruses called haemagglutinin.

Sir John Skehel, MRC scientist at Mill Hill, said: “We’ve tried every subtype of influenza A and it interacts with them all.

“We eventually hope it can be used as a therapy by injecting the antibody to stop the infection.”

Professor Antonio Lanzavecchia, director of the Institute for Research in Biomedicine, Switzerland, said: “As the first and only antibody which targets all known subtypes of the influenza A virus, FI6 represents an important new treatment option.”

When mice were given FI6, the antibody was “fully protective” against a later lethal doses of H1N1 virus.

Mice injected with the antibody up to two days after being given a lethal dose of the virus recovered and survived.

This is only the antibody, however, not the vaccine.

A vaccine would need to trigger the human body’s immune system to produce the antibody itself.

Sir John said the structure of the antibody and how it interacted with haemagglutinin had been worked out, which would help in the search for a vaccine, but that was “definitely years away”.

Professor John Oxford, a virologist at Queen Mary, University of London, said: “It’s pretty good if you’ve got one against the whole shebang, that’s a good step forward.”

Source: http://www.bbc.co.uk/news/health-14324901

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Proteus Syndrom Gene Variant Identified

Last Updated on Thursday, 28 July 2011 11:34 Written by admin Thursday, 28 July 2011 11:34

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

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

Last Updated on Wednesday, 27 July 2011 04:38 Written by admin Wednesday, 27 July 2011 04:38

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/

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Smelly socks tested in Tanzania as way to prevent malaria

Last Updated on Thursday, 14 July 2011 11:49 Written by admin Thursday, 14 July 2011 11:49

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

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Daily pill can prevent HIV infection

Last Updated on Thursday, 14 July 2011 11:36 Written by admin Thursday, 14 July 2011 11:36

The partners of people who have HIV can protect themselves from infection by taking a once-daily pill, two groundbreaking studies in Botswana, Kenya and Uganda have shown.

The discovery could bring work to combat Aids close to a “tipping point”, experts say. Attempts to promote condom use to protect against HIV in the hardest-hit parts of the world, and particularly Africa, have hit cultural barriers and had limited success.

But now it appears that men or women who know – or suspect – their partner has HIV could protect themselves, secretly if necessary. The larger study, involving 4,758 “discordant” couples (where one has HIV but the other has not) in Kenya and Uganda, led by the University of Washington’s International Clinical Research Centre, shows that those taking a single daily tablet of the Aids drug tenofovir had 62% fewer infections and those who took a pill combining tenofovir and emtricitabine had 73% fewer infections than those who took a placebo pill.

The drugs have few side-effects, which is important if they are to be given to healthy individuals. Both are made by Gilead, which has licensed their manufacture to generic companies in the developing world, allowing them to produce cheap copies – so this is a relatively inexpensive intervention.

“This study demonstrates that antiretrovirals are a highly potent and fundamental cornerstone for HIV prevention and should become an integral part of global efforts for HIV prevention,” said Dr Connie Celum, professor of global health and medicine at the university and principal investigator of the study, known as the Partners PrEP Study, which was funded by the Bill and Melinda Gates Foundation.

The second study in Botswana was conducted by the United States Centres for Disease Control. It followed 1,200 heterosexual men and women without HIV who received either a once-daily tenofovir/emtricitabine tablet or a placebo pill. The antiretroviral tablet reduced the risk of acquiring HIV infection by roughly 63% overall.

“This is a major scientific breakthrough which re-confirms the essential role that antiretroviral medicine has to play in the Aids response,” said Michel Sidibé, Executive Director of the Joint United Nations Programme on HIV/Aids (UNAids). “These studies could help us to reach the tipping point in the HIV epidemic.”

The news follows hard on the heels of another very significant finding – that people with HIV who are taking combinations of antiretroviral drugs not only stay healthy themselves but are unlikely to infect their partner.

The two pieces of research give a massive boost to the cause of rolling out more Aids drugs and treating people at the earliest stage of their illness.

“Effective new HIV prevention tools are urgently needed, and these studies could have enormous impact in preventing heterosexual transmission,” said Dr Margaret Chan, WHO’s director general. “WHO will be working with countries to use the new findings to protect more men and women from HIV infection.”

Source: http://www.guardian.co.uk/world/2011/jul/14/hiv-daily-pill-breakthrough

Posted under Antibiotics, Cell Analysis, Discoveries, Innovations and Patents, Drug Development, HIV Research, Medicinal Chemistry, New Drugs, New Products, Press Releases, R & D, Reports | Comments Off

A deadly new reason to avoid deer ticks

Last Updated on Monday, 11 July 2011 02:35 Written by admin Monday, 11 July 2011 02:35

Move over, Lyme disease: Another tick-borne illness is on the rise in various parts of the country, and this one can kill.

Known as babesiosis, the disease is caused by a microscopic parasite that attacks blood cells, causing flu-like symptoms that can make it difficult to accurately diagnose. Like Lyme disease, which is caused by bacteria, babesia microti parasites are carried by deer ticks.

First documented in Massachusetts in 1969, the once-obscure babesiosis has surfaced as a significant public health threat in parts of the Northeast and Upper Midwest over the last several years. A recent study in the journal Emerging Infectious Diseases, published by the U.S. Centers for Disease Control and Prevention, revealed that between 2001 and 2008 cases climbed from six to 119 in New York’s Lower Hudson Valley — a 20-fold regional increase.

And many cases may be escaping detection, experts say.

“I think it’s underreported. One of the reasons we’re seeing more about it is because people are becoming more aware,” said Dr. Peter Krause, a babesiosis researcher and senior research scientist at the Yale University School of Public Health. “The theory is that it’s spreading from east to west, as if you were dropping a pebble in a pond and it spread outward geographically.”

About 1,000 cases are reported annually in affected locales, Krause said, but many people with babesiosis have no symptoms and never know they’re harboring the parasite. For others, symptoms can include high fever, severe headache, fatigue, chills, and muscle aches and pains. It is treated with antimicrobial drugs, such as antibiotics.

People with compromised immune systems — including the elderly and those with cancer, HIV or no spleens — are especially at risk of potentially deadly complications such as organ failure. Between 10 percent and 20 percent of patients in those populations die as a result, Krause said.

The more prolific Lyme disease causes similar symptoms in early stage cases but is easier to diagnose by its telltale bullseye rash, said Dr. Barbara Herwaldt, a medical epidemiologist at the CDC who specializes in parasitic conditions.

Deer are pivotal to the life cycle of ticks carrying the babesia microti parasite by serving as a blood meal, shelter and a place to mate, Krause said. Ticks also feed on birds, who serve as carriers for Lyme disease, which affects the entire continental United States. Fortunately for humans, birds don’t carry babesia microti.

Krause noted that ticks need a moist climate to thrive, so dry states such as Arizona are not likely to see babesiosis cases caused by tick bites. But the disease can potentially spread to all states in an even sneakier way — through the blood supply.

Although a blood screening test is in trials, Krause said, donors are currently only asked if they have had babesiosis, and those who harbored it but never showed symptoms can pass it through their donated blood. And because most blood recipients are already physically compromised, babesiosis has about a 30 percent mortality rate in that group, he said.

“Getting babesiosis through the blood supply is a rare event and people shouldn’t panic,” he said. “I don’t think it will reach a crisis level, but it’s still a concern.”

To help prevent babesiosis, the CDC advises people with compromised immune systems or other vulnerabilities to avoid tick-infested wooded areas, particularly during warm months. The agency also recommends that everyone walk in the middle of trails and avoid bushy areas with lots of leaves or tall grasses and to use the repellent DEET and pre-treat clothes with an insect repellent containing permethrin before going outdoors.

The CDC also recommends doing full-body checks and showering within a few hours of being in the woods, as well as tossing used clothes in the dryer to kill any ticks that might be hiding there.

The authors of the study also advised clinicians to consider babesiosis in patients who have been exposed to ticks or received blood products and who show up for treatment with a fever and anemia resulting from the destruction of red blood cells.

Source: http://yourlife.usatoday.com/health/story/2011/07/A-deadly-new-reason-to-avoid-deer-ticks/49212700/1

Posted under Cell Analysis, Discoveries, Innovations and Patents, Medicinal Chemistry, North America, Press Releases, R & D, Reports, USA and Canada | Comments Off

Who wants to live forever? Scientist sees aging cured

Last Updated on Tuesday, 5 July 2011 11:56 Written by admin Tuesday, 5 July 2011 11:56

(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

Posted under Cell Analysis, Discoveries, Innovations and Patents, DNA Reasearch, Medicinal Chemistry, Research Projects, Stem Cell Research | Comments Off

The Second Disease To Ever Be Globally Eradicated: Rinderpest

Last Updated on Thursday, 30 June 2011 11:06 Written by admin Thursday, 30 June 2011 11:06

One of the greatest scourges of human history is no more. For only the second time, modern public health practices have managed to eradicate a pandemic illness of global reach. The first was smallpox. Now what? AIDS? TB? No. Today, the world’s cattle are safe from rinderpest.

If you’ve never heard of rinderpest, it’s likely because you live in America, where thanks to the quarantine of distance and history the disease never established itself. But in the old world, cattle have kept company with humans for some 8,000 years, often in settings of extraordinary intimacy. Farm families throughout Europe lived in crofts, homes that doubled as stables; pastorlists like the Nuer people of Sudan, who drink not only cows’ milk but their blood as well, rely on cattle to supply nearly all their needs.

Through the many generations of coexistence, humans and their domesticated herds have shared their illnesses; smallpox, the only other disease eradicated by modern public health practices, likely began among cattle (the first smallpox vaccines were made by scraping matter from lesions on cows). In rinderpest, we humans returned the favor–scientists now think that the disease, a relative of measles, evolved from the human pathogen as recently as a thousand years ago.

Although no human ever fell ill from rinderpest, its toll on our species has been considerable. With mortality rates among afflicted herds approaching 90 percent, rinderpest outbreaks quickly starved populations of cattle-dependent farmers. In East Africa, its introduction had much the same effect as human diseases did in the New World in the wake of first European contact, laying waste to entire societies and rendering them defenseless in the face of colonialism. It has been blamed for the stagnation of agricultural economies and the rise and fall of empires. Though the last case was seen in 2001, farmers can now rest easy knowing the disease is fully contained. The benefits of rinderpest-free herds to agrarian economies will only grow with time.

Rinderpest’s eradication depended on recent innovations in medical practice. It took a combination of technical advances, including a new form of vaccine that doesn’t need to be refrigerated; and culturally-sensitive public health protocols, relying on local veterinary assistants rather than pith-helmeted foreign specialists to manage the disease in its far-flung pastures. Its eradication is evidence of one of the curious insights of modern public health: that while disease is global, medicine often takes a village.

Source: http://www.fastcompany.com/1764227/the-eradication-of-rinderpest

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Coffee buzz protects brain from Alzheimer’s

Last Updated on Thursday, 30 June 2011 11:00 Written by admin Thursday, 30 June 2011 11:00

For years we’ve been told that caffeinated coffee was bad for us. It’s unhealthy and addictive, doctors warned. But as vindication for all who stuck by their energizing elixir, a new study shows that guzzling caffeinated coffee may actually be good for our brains. In fact, it may help keep Alzheimer’s at bay.

The study, which was published early online in the Journal of Alzheimer’s Disease, was in mice whose DNA had been tweaked to contain a human Alzheimer’s gene. Just like humans with familial Alzheimer’s, these mice become increasingly forgetful as they age.

Amazingly, the equivalent of four to five cups of caffeinated coffee every few days led to much improved memories in the Alzheimer’s mice, says study co-author Gary Arendash, a scientist at the Florida Alzheimer’s Disease Research Center in Tampa.

Earlier research by Arendash and his colleagues showed that caffeine could at least partially block the production of beta amyloid, the sticky protein that clogs the brains of Alzheimer’s patients. They also found that a substance called granulocyte-colony stimulating factor, or GCSF, sparked the production of new axons, the communication cables that link nerve cells together, as well as new nerve cells themselves.

What’s really interesting is that caffeinated coffee — but not decaf — boosted the production of GCSF.

For the new study, Arendash and his colleagues “treated” healthy mice and Alzheimer’s mice with either caffeinated or decaffeinated coffee. Then the researchers ran a test to see if either beverage led to better memories.

The test they used mimics one that is given to humans to diagnose Alzheimer’s. In that test, people are given a bag of objects to look through (we’ll call that Bag A). And then they’re shown another bag of objects (Bag B). Later on, they’re asked to remember what was in Bag A.

Studies have shown that people with Alzheimer’s have a tough time remembering what was in Bag A because the distraction of looking through the objects from Bag B gets in the way of storing the contents of A in their long term memories. That’s generally not a problem for people with healthy brains.

The two part mouse test involved water mazes. The mice has to find — and remember — the location of a submerged platform in a tub of water that is deep enough that they need to swim till they find the platform.

After they find the platform in one tub, they’re moved to another tub where they have to find yet another platform. Mice with Alzheimer’s generally have a tough time remembering the location of the first platform when they’re placed in the original tub. But in Arendash’s study, Alzheimer’s mice that got caffeinated coffee had memories that were just as good as those of normal mice.

Lest you dismiss this study because it’s just in rodents, Arendash says he’s got new data in humans. That data is still being analyzed, he says, but so far it looks like caffeinated coffee has the same impact in people as it does in mice.

Source: http://bodyodd.msnbc.msn.com/_news/2011/06/28/6968218-coffee-buzz-protects-brain-from-alzheimers

Posted under Alzheimer's disease, Cell Analysis, Discoveries, Innovations and Patents, North America, R & D, Reports, Research Projects, USA and Canada | Comments Off

Hemophilia Is Target of Therapy on Genome

Last Updated on Monday, 27 June 2011 11:13 Written by admin Monday, 27 June 2011 11:13

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

Posted under Cell Analysis, Discoveries, Innovations and Patents, DNA Reasearch, HIV Research, North America, Research Projects, USA and Canada | Comments Off

Experimental Type 1 diabetes vaccine fails during second step of trial

Last Updated on Monday, 27 June 2011 11:07 Written by admin Monday, 27 June 2011 11:07

The quest for a vaccine to stop Type 1 diabetes in its tracks has hit a roadblock.

An experimental drug failed in the second step of a three-phase trial on 145 American and Canadian patients who had just been diagnosed with the disease.

The vaccine is based on an enzyme that is targeted by a diabetes patient’s immune system.

Researchers hoped the vaccine would train the immune system to not attack the enzyme – a process that destroys the pancreas’ insulin-producing cells.

But according to a study published by the medical journal The Lancet on Monday, patients who got the vaccine experienced no difference in the progression of the disease.

The vaccine was aimed at Type 1 diabetes, which used to be known as juvenile diabetes and affects less than 10% of people with the disease.

Most sufferers have what’s known as adult-onset or Type 2 diabetes.

New research shows vitamin D may ward off those at risk for Type 2 from actually developing the disease.

A study released over the weekend revealed that patients with the high levels of the vitamin were 25% less likely than those with the lowest amounts to get diabetes.

Scientists theorize that vitamin D may help the body produce more insulin or increase the body’s sensitivity to insulin.

Source: http://www.nydailynews.com/lifestyle/health/2011/06/27/2011-06-27_experimental_type_1_diabetes_vaccine_fails_during_second_step_of_trial.html?r=news/national

Posted under Clinical Trials, Discoveries, Innovations and Patents, Drug Development, New Products, North America, R & D, Reports, USA and Canada | Comments Off

New Drug Effectively Treats Hepatitis C

Last Updated on Thursday, 23 June 2011 04:36 Written by admin Thursday, 23 June 2011 04:36

WEDNESDAY, June 22 (HealthDay News) — The recently approved drug Incivek, combined with two standard drugs, is highly effective at treating hepatitis C, a notoriously difficult-to-manage liver disease, two new studies show.

The drug works not only in patients just starting treatment, but in those who failed earlier treatment, the research found.

The hepatitis C virus can lurk in the body for years, causing liver damage, cirrhosis and even liver failure.

“This is a significant advance in the treatment of hepatitis C,” said Dr. David Bernstein, chief of the division of gastroenterology, hepatology and nutrition at North Shore University Hospital in Manhasset, N.Y., who was not involved in either study.

“We know that if we can get rid of the hepatitis C, we can prevent the progression of [liver] disease,” he said. “This means we can prevent the progression of cirrhosis, we can prevent the development of cancer and also prevent the need for liver transplantation in a large number of people.”

Incivek (telaprevir) was approved by the U.S. Food and Drug Administration in May and is the second drug in a class of drugs called protease inhibitors to be approved to fight hepatitis C. The other drug, called Victrelis (boceprevir), was also approved in May.

The standard treatment for hepatitis C has been a combination of two drugs, pegylated-interferon and ribavirin, which are given for a year. If protease inhibitors such as Incivek are added to the mix, the “viral cure” rate improves and the treatment time is reduced to six months, researchers found.

Both reports were published in the June 23 online edition of the New England Journal of Medicine.

In one study, a Phase 3 trial known as ADVANCE, patients were randomly assigned to either a placebo or the treatment in a double-blind study, which means that neither the patients nor the researchers know who’s getting the drug and who’s getting a sham treatment. This type of study is considered the gold standard for clinical research.

In the ADVANCE trial, 1,088 patients with hepatitis C who had never been treated for the condition were randomly assigned to standard therapy for 48 weeks, or telaprevir combined with standard therapy for eight or for 12 weeks, followed by standard therapy alone for a total treatment time of either 24 or 48 weeks.

The researchers found that 79 percent of those receiving Incivek for the longest period (24 weeks) had a “sustained response,” which basically means their hepatitis C was contained. Among those receiving standard care, 44 percent had a sustained response, the researchers noted.

“We have entered a new era of therapy for hepatitis C, which enables us to cure many more patients than we could before,” said lead researcher Dr. Ira M. Jacobson, from Weill Cornell Medical College in New York City.

Incivek needs to be given along with pegylated-interferon and ribavirin, Jacobson said. The researchers learned early on that Incivek alone reduces the level of the virus, but later the virus can become resistant to the drug, he said.

For the second study, called the REALIZE trial, 663 patients with hepatitis C who had failed standard therapy were divided into three groups. One group received Incivek plus standard therapy, another group was started on pegylated-interferon and ribavirin and then had Incivek added. The third group received standard therapy alone.

Here, the researchers found up to an 88 percent sustained response in patients receiving Incivek, compared with a 24 percent sustained response in the standard treatment group.

“These drugs represent a real milestone in the treatment of this disease,” said lead researcher Dr. Stefan Zeuzem, a professor of medicine at J.W. Goethe University Hospital in Frankfurt, Germany.

“There were very limited treatment options in the past, but now many patients have excellent chances to be cured, even if they already have advanced disease,” he said.

Bernstein noted that in the past, these patients could only be treated with more of the standard therapy for a longer period and the “cure” rate was only 10 percent. “Now you can treat these patients for six months with cure rates approaching 90 percent,” he said. “You are really offering hope to a large number of patients.”

The side effects of the medications include skin rashes, anemia, fatigue, itching, nausea, diarrhea, vomiting and taste changes. Some side effects were serious enough to cause a few participants to drop out, according to the study.

Incivek, made by Vertex Pharmaceuticals Inc., is sold to wholesalers for $49,200 for a four-week course of treatment, said Vertex spokeswomen Nikki Levy.

While both Incivek and Victrelis are important breakthroughs in the treatment of hepatitis C, new drugs with even fewer side effects and perhaps shorter treatment times are in clinical trials, Bernstein said.

Hepatitis C affects almost 4 million Americans, most of whom don’t know they’re infected. Often there are no symptoms, but it is the leading cause of liver transplantation in the United States and is linked to as many as 12,000 deaths a year, the researchers say.

Source: http://health.usnews.com/health-news/family-health/digestive-disorders/articles/2011/06/23/new-drug-effectively-treats-hepatitis-c?PageNr=1

Posted under Discoveries, Innovations and Patents, Drug Development, FDA News, Hepatitis Research, Medicinal Chemistry, New Drugs, New Products, R & D | Comments Off

Protein ‘helps predict Alzheimer’s risk’

Last Updated on Thursday, 23 June 2011 12:53 Written by admin Thursday, 23 June 2011 12:53

A protein in spinal fluid could be used to predict the risk of developing Alzheimer’s disease, according to German researchers.

Patients with high levels of the chemical – soluble amyloid precursor protein beta – were more likely to develop the disease, they found.

Doctors said in the journal Neurology this was more precise than other tests.

Alzheimer’s Research UK said early diagnosis was a key goal, and the study represented a potential new lead.

Doctors analysed samples of spinal fluid from 58 patients with mild cognitive impairment, a memory-loss condition which can lead to Alzheimer’s.

The patients were followed for three years. Around a third developed Alzheimer’s.

Those who developed the illness had, on average, 1,200 nanograms/ml of the protein in the spinal fluid at the start of the study.

Those who did not started with just 932 nanograms/ml.

Beta amyloid proteins have already been implicated in Alzheimer’s itself, but not as a “predictor” of the disease.

The researchers said that a combination of soluble amyloid precursor protein beta, defective tau proteins, which are involved in the structure of brain cells, and a patient’s age was 80% accurate in predicting the onset of the disease.

Early diagnosis crucial

There is no cure for Alzheimer’s disease. If a treatment is developed, it is thought that it would need to be delivered early, before any permanent damage was done.

Dr Robert Perneczky, from the Technical University Munich, said: “Being able to identify who will develop Alzheimer’s disease very early in the process will be crucial in the future.

“Once we have treatments that could prevent Alzheimer’s disease, we could begin to treat very early and hopefully prevent the loss of memory and thinking skills that occurs with this devastating disease.”

More than 800,000 people have dementia in the UK, and that figure is expected to rise as populations get older.

Rebecca Wood, chief executive of Alzheimer’s Research UK, said: “The ability to diagnose Alzheimer’s early is a key goal for doctors and researchers. This small study provides a potential new lead to follow up.

“We will need to see larger trials before we can know how accurate this method could be as a diagnostic test. It will also be important to see how measurements of these proteins compare to those found in healthy people.”

Source: http://www.bbc.co.uk/news/health-13875984

Posted under Alzheimer's disease, Discoveries, Innovations and Patents, Europe, Europe, Medicinal Chemistry, R & D, Reports | Comments Off

Genome Maps Solve Medical Mystery For Calif. Twins

Last Updated on Thursday, 16 June 2011 10:51 Written by admin Thursday, 16 June 2011 10:51

Ever since scientists began to sequence the entire genomes of individuals —beginning with those of Nobelist James Watson and scientific entrepreneur J. Craig Venter in 2007 — skeptics have wondered just how useful this elegant and expensive trick would become.

A pair of 14-year-old twins, Alexis and Noah Beery, now provide a compelling answer, even if it’s not yet clear how generalizable their case is to others with genetic disorders.

Whole-genome sequencing has enabled doctors to provide the Beery twins with a simple, highly effective treatment for a rare condition called DRD, or dopa-responsive dystonia. The tale of their cure appears in this week’s issue of the journal Science Translational Medicine.

The twins were diagnosed with cerebral palsy at age two. But their mother, Retta Beery, didn’t think that was correct. For one thing, Alexis’s contorted posture and jerky movements always seemed to be better in the morning and increased as the day went on.

Turns out DRD is known for these diurnal variations, as Retta found out through dogged research. That led to a diagnosis of DRD when the twins were five. Since DRD was thought to be a deficiency of the neurotransmitter dopamine, low doses of a drug called L-dopa (also used for Parkinson’s disease) rather miraculously made the twins’ “cerebral palsy” go away within days.

But other symptoms persisted and worsened. At age 14, Noah had hand tremors, awkwardness and attentional problems. More alarmingly, Alexis had breathing problems due to spasms in her larynx. But when doctors probed for an explanation of these symptoms, the twins tested negative for known mutations of two genes known to be involved in DRD.

As it happens, the twins’ father, Joe Beery, works for a California biotech company that makes DNA sequencing machines. So the parents wondered if a deep dive into their twins’ DNA might explain the nature of their particular genetic defect.

Scientists at Baylor College of Medicine, a pioneer in whole-genome sequencing of individuals, thought it was worth a go. They sequenced the genomes of the twins, their older brother, their parents and their grandparents.

Comparing the results, the researchers found that the twins both inherited a gene variant from each parent that, together, led them to have low levels of not just dopamine but two other neurotransmitters, serotonin and noradrenalin.

The twins’ neurologist, Jennifer Friedman of Rady Children’s Hospital in San Diego, suggested giving the teenagers a supplement called 5-HTP that’s a precursor for serotonin.

Together with the L-dopa, the additional supplement has improved Alexis’s breathing point to the point that she’s now running track again. Noah’s handwriting and athletic performance have improved, and he’s better able to focus in school.

And there’s an intriguing bonus. Scientists think the gene mutation that the Beery twins inherited from their mother may be responsible for a pattern of a neuromuscular disease called fibromyalgia in her family. Fibromyalgia sometimes responds to anti-depressants called SSRIs that raise serotonin levels.

If that hypothesis pans out, it would suggest that rare genetic disorders such as DRD are just the most dramatic manifestation – in people who inherit a double dose of certain gene variants – of much more common disorders such as fibromyalgia among people who have a single copy of the mutation.

Study authors say the Beerys’ case shows how genomics will ultimately revolutionize medicine by making diagnosis more precise and pointing toward life-changing treatments. Other cases are beginning to pop up, such as a Wisconsin boy whose rare disease was diagnosed by whole-genome sequencing and subsequently treated with a bone marrow transplant. (His story appeared in a Pulitzer Prize-winning series by the Milwaukee Journal-Sentinel.)

Cost is still a big obstacle. At the time the Beery family’s genomes were sequenced, it cost around $100,000 per person. Dr. Richard Gibbs of Baylor says now, less than two years later, it would cost about half as much – less than $10,000 for the actual sequencing, plus the cost of computer processing of the results and validation.

The skeptics also point out that not all genetic insights from sequencing will lead to such cheap, simple and effective treatments as the Beery twins got.

Source: http://www.npr.org/blogs/health/2011/06/16/137204964/genome-maps-solve-medical-mystery-for-calif-twins

Posted under Cell Analysis, Discoveries, Innovations and Patents, DNA Reasearch, Genetics & Pharmacogenetics, Medicinal Chemistry, North America, Research Projects, USA and Canada | Comments Off

Premature aging seen as issue for AIDS survivors

Last Updated on Tuesday, 14 June 2011 03:19 Written by admin Tuesday, 14 June 2011 03:19

SAN FRANCISCO (AP) — Having survived the first and worst years of the AIDS epidemic, when he was losing three friends to the disease in a day and undergoing every primitive, toxic treatment that then existed, Peter Greene is grateful to be alive.

But a quarter-century after his own diagnosis, the former Mr. Gay Colorado, now 56, wrestles with vision impairment, bone density loss and other debilitating health problems he once assumed he wouldn’t grow old enough to see.

“I survived all the big things, but now there is a new host of things. Liver problems. Kidney disease. It’s like you are a 50-year-old in an 80-year-old body,” Greene, a San Francisco travel agent, said. “I’m just afraid that this is not, regardless of what my non-HIV positive friends say, the typical aging process.”

Even when AIDS still was almost always fatal, researchers predicted that people infected with HIV would be more prone to the cancers, neurological disorders and heart conditions that typically afflict the elderly. Thirty years after the first diagnoses, doctors are seeing these and other unanticipated signs of premature or “accelerated” aging in some long-term survivors.

Government-funded scientists are working to tease apart whether the memory loss, arthritis, renal failure and high blood pressure showing up in patients in their 40s and 50s are consequences of HIV, the drugs used to treat it or a cruel combination of both. With people over 50 expected to make up a majority of U.S. residents infected with the virus by 2015, there’s some urgency to unraveling the “complex treatment challenges” HIV poses to older Americans, according to the National Institutes of Health.

“In those with long-term HIV infection, the persistent activation of immune cells by the virus likely increases the susceptibility of these individuals to inflammation-induced diseases and diminishes their capacity to fight certain diseases,” the federal health agency’s chiefs of infectious diseases, aging and AIDS research wrote, summing up the current state of knowledge on last September’s National HIV/AIDS and Aging Awareness Day. “Coupled with the aging process, the extended exposure of these adults to both HIV and antiretroviral drugs appears to increase their risk of illness and death from cardiovascular, bone, kidney, liver and lung disease, as well as many cancers not associated directly with HIV infection.”

In San Francisco, where already more than half of the 9,734 AIDS cases are in people 50 and over, University of California, San Francisco AIDS specialists are collaborating with geriatricians, pharmacists and nutritionists to develop treatment guidelines designed to help veterans of the disease cope with getting frail a decade or two ahead of schedule and to remain independent for as long as possible.

“Wouldn’t it be helpful to be able to say, are you at high risk, low risk or moderate risk for progressing to dependency in the next five, the next 10 years, being less mobile, less able to be functional in the workplace. Are you going to be safe in your home, are you going to remember to take all those medications? How are they going to interact?” explained Dr. Malcolm John, who directs UCSF’s HIV clinic. “All those questions need to be brought into the HIV field at a younger age.”

Research so far suggests that HIV is not directly causing conditions that mimic old age, but hastens patients toward ailments to which they may have been genetically or environmentally predisposed. Plus, their immune systems are being weakened over time even when they are being successfully treated for AIDS, John said.

“That’s probably true for a lot of these things. We aren’t saying HIV’s starting the problem, but it’s added fuel on top,” he said.

Stokes, a patient of John’s who goes by only his last name, is a prime example. At 53, HIV-positive since 1985 and in substance abuse recovery for the last 11 years, he says he is happier than he ever has been. Yet the number of ailments for which he is being treated would be more commonly found in someone 30 years his senior: a condition called Ramsay Hunt syndrome that causes facial paralysis, a rare cartilage disorder for which he has undergone four ear surgeries, bone death in the hip and shoulder, deterioration of his heart muscle, osteoporosis and memory loss.

A specialist recently diagnosed a Kaposi’s sarcoma spot on Stokes’ ankle. Although the cancer is not life-threatening, the sight of young men disfigured by KS lesions was a harbinger of the early AIDS crisis, and its presence on his own body is unsettling.

At his therapy group for men with HIV, aging “comes up frequently,” he said. “I say, ‘Just think what we have come through to have a life today.’” At the same time, he acknowledges sometimes feeling self-conscious about his physical appearance and worries if “people are not attracted to me and unwilling to go the length of what it means to be with me, no matter how brilliant my mind or my zest for life.”

Loneliness, financial worries and concerns about who will care for them and where can weigh on long-term AIDS survivors in the same way as all adults living in a society that values youth, Charles Emlet, a social work professor at the University of Washington, Tacoma, said.

As they get older and sicker, many feel “doubly stigmatized,” he said. Some people who have lived with the virus for a long time have been getting by on private disability benefits that will run out when they turn 65, forcing them to move to less expensive locations or to consider turning to estranged family members. Like soldiers from a distant war, many lost partners and their closest friends to AIDS.

Such emotional side effects, combined with the physical toll of managing chronic health problems, put older AIDS patients at risk for depression. At the same time, Emlet has uncovered evidence that a majority of long-term survivors also share another trait that typically comes with advanced age: that is, the ability to draw strength from their difficult experiences.

“The older adults I’ve interviewed, many of them talk about how much it means to them to give back, to do something positive with the years they never expected to have,” he said.

Peter Greene can relate to that. At times, like the days he is so exhausted he can’t get out of bed or the pain from his multiple maladies is too intense, he asks himself “the Carrie Bradshaw question–are we really lucky to still be alive?”

As frightening and uncertain as this phase of AIDS is, he thinks he knows the answer.

“I’ve tried to make the time I have count, and really, now that I have the body of an 80-year-old, I probably have the wisdom of an 80-year-old as well, which counts for a lot,” Greene said. “Everything becomes clear at the end of your life and in some ways, thinking you’ve been dying all these years, you get moments of clarity that I don’t think everyone gets.”

Source: http://www.google.com/hostednews/ap/article/ALeqM5jSFCmOu9Y714ci26I_SOCRQvDDSQ?docId=ad4d0382cdcf430c8e325be4dd84d540

Posted under Discoveries, Innovations and Patents, HIV Research, Reports | Comments Off

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