Geron Corporation (Nasdaq: GERN) has reported its scientists and collaborators have demonstrated that human embryonic stem cell (hESC)-derived cardiomyocytes improve heart function when transplanted after myocardial infarction.
Published online in Nature Biotechnology, the landmark study is the first to document the potential clinical utility of regenerating damaged heart muscle by injecting hESC-derived cardiomyocytes directly into the site of the infarct. In addition, the research confirms the effectiveness of a scalable production system that enables Geron to manufacture the cardiomyocytes for use in ongoing large animal studies and, ultimately, testing in humans.
The study describes the feeder- and serum-free, scalable production of hESC-derived cardiomyocytes, their survival in the infarct zone of rats when transplanted four days after infarction, and echocardiographic and MRI evidence of significant improvement in cardiac structure and contractile function. Geron's scientists conducted the study in collaboration with Charles Murry, M.D., Ph.D., and Michael Laflamme, M.D., Ph.D., at the University of Washington.
"This is one of the most important publications on hESCs for Geron to date," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "Our cardiomyocytes are the first human cardiac cells shown to survive after injection into an infarcted ventricle and to produce significant improvement in heart function. hESCs are the only cell type shown definitively to form cardiomyocytes."
Approximately 5.2 million people in the United States suffer from heart failure, and approximately 865,000 people experience myocardial infarction each year. About 36% of this population progresses to heart failure within five years of a first infarction. More than one-third of all heart failure patients die within two years of diagnosis.
"We're developing our cardiomyocyte product, GRNCM1, to address the large unmet need in heart failure," Dr. Okarma added. "We expect GRNCM1 to be our second hESC-derived cell type to enter clinical development."
Production and Characterization of hESC-derived Cardiomyocytes
In the study, researchers produced human cardiomyocytes from hESCs using a sequential, directed differentiation protocol that did not rely on serum or feeder cells. The procedure was scalable and efficient, with each hESC producing approximately three human cardiomyocytes. After final enrichment, greater than 80% of the cells were cardiomyocytes. The hESC-derived cardiomyocytes displayed surface and intracellular markers, as well as electrophysiologic and pharmacologic properties consistent with human cardiomyocytes, the majority of which represented ventricular cardiomyocytes.
Engraftment Following Transplantation
To enable survival in the heart, the hESC-derived cardiomyocytes were suspended in a cocktail of survival factors that had been experimentally determined to dramatically enhance cell survival after injection into the infarcted ventricular wall. Four weeks later, tissue sections from the infarcted hearts were examined for the presence of the human cells. The vast majority of human cardiomyocytes were localized in the central region of the infarct, suggesting that the cells were capable of engraftment in the hostile environment of the infarct zone. Moreover, a portion of the cardiomyocytes was mitotic after injection, possibly enhancing their regenerative efficiency. The grafts also induced a brisk, host-derived angiogenic response: all the implants contained numerous capillaries lined with rat endothelial cells.
Safety
No teratomas, tumor masses, or aberrant structures were seen in any of the hearts receiving hESC-derived cardiomyocytes. A highly sensitive PCR assay was used to determine whether any hESC-derived cells had migrated to other non-cardiac organs. None were detected in brain, kidney, liver, lung or spleen, indicating the absence of migration of the injected cells from the heart.
Impact of Transplanted hESC-derived Cardiomyocytes on Cardiac Structure and Function
To assess the impact of injected cells on cardiac structure and function, all animals received echocardiography at baseline (two days after infarction but two days prior to cell injection) and at four weeks post cardiomyocyte implantation. All animals exhibited significant cardiac dysfunction two days post infarct. On average, left-ventricular end diastolic and systolic diameters increased by 10% and 42%, respectively, and fractional shortening decreased by 40% compared to uninfarcted controls.
Four days after infarction, animals were injected with 10 million hESC-derived cardiomyocytes suspended in the survival cocktail. Animals injected with either the survival cocktail alone, serum-free media without cells, or equivalent numbers of non-cardiac hESC-derived cells suspended in the survival cocktail served as control groups.
Echocardiography performed four weeks after cell implantation showed attenuation of left-ventricular end-diastolic and end-systolic diameters in animals receiving cardiomyocytes versus all three control groups. In addition, fractional shortening was significantly improved (0.01) in animals that received cardiomyocytes compared to all three control groups. MRI analysis showed improved left-ventricular ejection fraction (p=0.05) in the cardiomyocyte-treated rats compared to controls, as well as a 2.5-fold increase in systolic wall thickening in the infarct zone relative to controls (0.01).
Significance
This study is the first to document the potential clinical utility of regenerating damaged heart muscle by injecting hESC-derived cardiomyocytes directly into the infarct zone of the heart. The survival cocktail administered with the cells enables their long-term survival in the infarcted muscle. The injected cells stimulate endogenous blood vessel formation, possibly contributing to both cell survival and improved contractile function. The scalable production system allows for production runs at sufficient scale for large animal studies (ongoing) as well as for ultimate testing in humans.
Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure, diabetes and HIV/AIDS. The company is advancing an anti-cancer drug and a cancer vaccine that target the enzyme telomerase through multiple clinical trials. Geron is also the world leader in the development of human embryonic stem cell-based therapeutics, with its spinal cord injury treatment anticipated to be the first product to enter clinical development. For more information, visit geron/.
This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding potential applications of Geron's human embryonic stem cell technology constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Geron's periodic reports, including the quarterly report on Form 10-Q for the quarter ended June 30, 2007.
Contacts:
Investors: Matthew Haines, Russo Partners, LLC
At Geron: David L. Greenwood, Chief Financial Officer
Source: Sion Rogers
Russo Partners, LLC
четверг, 26 мая 2011 г.
Rules-Based Medicine, Inc. Announces Commercial Release Of Veripsych™, Diagnostic Aid For Recent Onset Schizophrenia
Rules-Based Medicine, Inc. (RBM), announced the widespread commercial availability of VeriPsych™, the first and only blood-based diagnostic test to aid in confirming the diagnosis of recent onset schizophrenia, a potentially devastating and costly mental illness that affects about 24 million people worldwide. VeriPsych is an innovative molecular diagnostic tool designed to complement the healthcare provider's clinical impression.
VeriPsych, based on the simultaneous measurement of 51 different protein and hormone biomarkers with an associated mathematical decision rule, compares the biomarker profile of a patient with suspected schizophrenia to that of patients with a confirmed diagnosis of schizophrenia. VeriPsych was developed by RBM to aid in the confirmation of the diagnosis of recent-onset schizophrenia, as reported in a study published in the May 2010 edition of Biomarker Insights.
"Schizophrenia is commonly associated with an inevitable disabling decline in mental and overall health, but we are understanding more and more that early therapeutic intervention can alter that prognosis," said Prof. Sabine Bahn, (Sa-bee-neh Baa hn) Director of the Cambridge Center for Neuropsychiatric Research in the United Kingdom and an RBM collaborator. "Ultimately, clearer and earlier diagnosis may lead to reduced disability, more effective treatment, improved patient outcomes and enhanced quality of life for patients."
Each year 1.3 million patients in the United States and 2 million patients in Europe present with early signs that could be schizophrenia. Signs of schizophrenia, which include hallucinations, confusion, delusions and cognitive deficits, are often indistinguishable from those of other mental health or central nervous system disorders, presenting frequent diagnostic challenges.
Diagnosis of schizophrenia is typically accomplished through the clinician's evaluation of symptoms. If left untreated or improperly treated, schizophrenia can lead to worsening patient conditions and ultimately poor outcomes. Neuropsychiatric conditions, including schizophrenia, are a leading cause of disability, accounting for approximately one third of years lost to disability among people aged 15 years and over.
"VeriPsych was developed through targeted research combining RBM's proprietary multiplexing technology and unique biomarker discovery capabilities, specifically in the area of mental illness," said RBM Chief Executive Officer Craig Benson. "We believe this test will be useful to mental healthcare providers seeking to confirm diagnostic decisions that can help patients and families living with mental illness. We are pleased to make this announcement during Mental Illness Awareness Week. VeriPsych is an important step in RBM's ongoing efforts to develop and provide quantitative diagnostic tools for healthcare providers treating patients with neuropsychiatric disorders."
About VeriPsych
VeriPsych is an objective blood-based molecular diagnostic tool that utilizes a proprietary set of 51 biomarker immunoassays. These biomarkers are associated with specific biochemical pathways, including inflammation, metabolism, and cell-to-cell signaling.
VeriPsych is a Laboratory Developed Test (LDT) that uses a decision rule to evaluate the similarity of a patient's biomarker pattern to that of patients with a medically confirmed diagnosis of schizophrenia. Its intended use is as an aid in the confirmation of the diagnosis of schizophrenia in patients with recent onset of symptoms and without co-morbidities such as diabetes, severe inflammation or autoimmune disease. It is not intended to provide a definitive diagnosis of schizophrenia.
VeriPsych was developed and its performance characteristics were determined by RBM. The test is performed by RBM in compliance with CLIA (Clinical Laboratory Improvement Amendments) regulations.
Source: Rules-Based Medicine, Inc
VeriPsych, based on the simultaneous measurement of 51 different protein and hormone biomarkers with an associated mathematical decision rule, compares the biomarker profile of a patient with suspected schizophrenia to that of patients with a confirmed diagnosis of schizophrenia. VeriPsych was developed by RBM to aid in the confirmation of the diagnosis of recent-onset schizophrenia, as reported in a study published in the May 2010 edition of Biomarker Insights.
"Schizophrenia is commonly associated with an inevitable disabling decline in mental and overall health, but we are understanding more and more that early therapeutic intervention can alter that prognosis," said Prof. Sabine Bahn, (Sa-bee-neh Baa hn) Director of the Cambridge Center for Neuropsychiatric Research in the United Kingdom and an RBM collaborator. "Ultimately, clearer and earlier diagnosis may lead to reduced disability, more effective treatment, improved patient outcomes and enhanced quality of life for patients."
Each year 1.3 million patients in the United States and 2 million patients in Europe present with early signs that could be schizophrenia. Signs of schizophrenia, which include hallucinations, confusion, delusions and cognitive deficits, are often indistinguishable from those of other mental health or central nervous system disorders, presenting frequent diagnostic challenges.
Diagnosis of schizophrenia is typically accomplished through the clinician's evaluation of symptoms. If left untreated or improperly treated, schizophrenia can lead to worsening patient conditions and ultimately poor outcomes. Neuropsychiatric conditions, including schizophrenia, are a leading cause of disability, accounting for approximately one third of years lost to disability among people aged 15 years and over.
"VeriPsych was developed through targeted research combining RBM's proprietary multiplexing technology and unique biomarker discovery capabilities, specifically in the area of mental illness," said RBM Chief Executive Officer Craig Benson. "We believe this test will be useful to mental healthcare providers seeking to confirm diagnostic decisions that can help patients and families living with mental illness. We are pleased to make this announcement during Mental Illness Awareness Week. VeriPsych is an important step in RBM's ongoing efforts to develop and provide quantitative diagnostic tools for healthcare providers treating patients with neuropsychiatric disorders."
About VeriPsych
VeriPsych is an objective blood-based molecular diagnostic tool that utilizes a proprietary set of 51 biomarker immunoassays. These biomarkers are associated with specific biochemical pathways, including inflammation, metabolism, and cell-to-cell signaling.
VeriPsych is a Laboratory Developed Test (LDT) that uses a decision rule to evaluate the similarity of a patient's biomarker pattern to that of patients with a medically confirmed diagnosis of schizophrenia. Its intended use is as an aid in the confirmation of the diagnosis of schizophrenia in patients with recent onset of symptoms and without co-morbidities such as diabetes, severe inflammation or autoimmune disease. It is not intended to provide a definitive diagnosis of schizophrenia.
VeriPsych was developed and its performance characteristics were determined by RBM. The test is performed by RBM in compliance with CLIA (Clinical Laboratory Improvement Amendments) regulations.
Source: Rules-Based Medicine, Inc
New findings in innate immunity may lead to treatments for atherosclerosis
Scientists are one step closer to deciphering the molecular signaling process controlling innate immunity with the
discovery that a molecule called IRAK1 regulates the expression of the anti-inflammatory cytokine IL-10. Because
atherosclerosis patients often have elevated IL-10 levels, IRAK1 may be a viable target for developing therapeutics for
atherosclerosis.
The research appears as the "Paper of the Week" in the December 3 issue of the Journal of Biological Chemistry, an American
Society for Biochemistry and Molecular Biology journal.
Innate immunity is the body's first response to infection, and it plays a major role in regulating infection, inflammation,
cell growth, and apoptosis. During an innate immune reaction, macrophages, dendritic cells, and epithelial cells use a set of
transmembrane receptors called Toll-like receptors (TLRs) to initiate signaling cascades.
"TLRs can sense diverse environmental cues and send signals downstream to a family of interleukin-1 receptor associated
kinases (IRAKs). These IRAKs then activate and/or regulate specific cytokine gene expression," explains Dr. Liwu Li of the
Wake Forest University School of Medicine.
However, the specificity of the TLR signaling process is not clearly understood. "In the past," says Dr. Li, "it was thought
that all IRAKs may play a somewhat redundant role in regulating the nuclear transcription factor NFкB and the expression of
pro-inflammatory cytokines such as IL-1beta and TNFalpha." However, mice that lack IRAK1 can still activate NFкB, suggesting
that IRAK1 may be involved in other activities.
Dr. Li and his colleagues discovered that IRAK1 actually activates a molecule called Signal Transducer and Activator of
Transcription 3, or Stat3, which in turn activates expression of the anti-inflammatory cytokine IL-10. The scientists also
found that IRAK1 can translocate into the nucleus and regulate the nuclear transcription of proteins. "Our finding sets IRAK1
apart from other IRAKs and elucidates a novel pathway in innate immunity regulation," says Dr. Li.
Because atherosclerosis patients usually have elevated serum IL-10 levels, the scientists also looked at IRAK1 levels in
blood from atherosclerosis patients. They found that IRAK1 is modified and localized to the nucleus in these patients,
indicating a possible link between IRAK1 regulation and the pathogenesis of atherosclerosis.
"Inflammation and infection have been increasingly shown to play a significant role in the pathogenesis and/or resolution of
atherosclerosis," explains Dr. Li. "Anti- inflammatory cytokines such as IL-10 may serve as a self protective mechanism to
prevent excessive inflammation and contribute to plaque stability. Indeed, patients with higher IL-10 serum levels have a
better chance of recovery. Therefore, elevated IRAK1 modification and IL-10 levels observed in atherosclerosis patients may
be a compensatory and self-protective mechanism."
Manipulating innate immunity may eventually be a therapeutic strategy for treating atherosclerosis. "Our study, as well as
others, indicates that innate immunity alteration plays a critical role in either the pathogenesis or resolution of
atherosclerosis. IRAK1 may provide a viable target for developing therapeutic interventions for atherosclerosis. Compounds or
strategies directed at preventing or enhancing IRAK1 modification and nuclear entry may hold great promise in treating
atherosclerosis," concludes Dr. Li.
Besides atherosclerosis, alterations in innate immunity can cause diabetes, cancer, and numerous other inflammatory
disorders. Further understanding of the innate immunity process may lead to development of therapies for these diseases as
well.
The Journal of Biological Chemistry's Papers of the Week is an online feature which highlights the top one percent of papers
received by the journal. Brief summaries of the papers and explanations of why they were selected for this honor can be
accessed directly from the home page of the Journal of Biological Chemistry online at jbc.
The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization
with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and
universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for
Experimental Biology. The Society's primary purpose is to advance the sciences of biochemistry and molecular biology through
its publications, the Journal of Biological Chemistry, The Journal of Lipid Research, Molecular and Cellular Proteomics, and
Biochemistry and Molecular Biology Education, and the holding of scientific meetings.
For more information about ASBMB, see the Society's website at asbmb.
Contact: Nicole Kresge
nkresgeasbmb
301-634-7415
American Society for Biochemistry and Molecular Biology
discovery that a molecule called IRAK1 regulates the expression of the anti-inflammatory cytokine IL-10. Because
atherosclerosis patients often have elevated IL-10 levels, IRAK1 may be a viable target for developing therapeutics for
atherosclerosis.
The research appears as the "Paper of the Week" in the December 3 issue of the Journal of Biological Chemistry, an American
Society for Biochemistry and Molecular Biology journal.
Innate immunity is the body's first response to infection, and it plays a major role in regulating infection, inflammation,
cell growth, and apoptosis. During an innate immune reaction, macrophages, dendritic cells, and epithelial cells use a set of
transmembrane receptors called Toll-like receptors (TLRs) to initiate signaling cascades.
"TLRs can sense diverse environmental cues and send signals downstream to a family of interleukin-1 receptor associated
kinases (IRAKs). These IRAKs then activate and/or regulate specific cytokine gene expression," explains Dr. Liwu Li of the
Wake Forest University School of Medicine.
However, the specificity of the TLR signaling process is not clearly understood. "In the past," says Dr. Li, "it was thought
that all IRAKs may play a somewhat redundant role in regulating the nuclear transcription factor NFкB and the expression of
pro-inflammatory cytokines such as IL-1beta and TNFalpha." However, mice that lack IRAK1 can still activate NFкB, suggesting
that IRAK1 may be involved in other activities.
Dr. Li and his colleagues discovered that IRAK1 actually activates a molecule called Signal Transducer and Activator of
Transcription 3, or Stat3, which in turn activates expression of the anti-inflammatory cytokine IL-10. The scientists also
found that IRAK1 can translocate into the nucleus and regulate the nuclear transcription of proteins. "Our finding sets IRAK1
apart from other IRAKs and elucidates a novel pathway in innate immunity regulation," says Dr. Li.
Because atherosclerosis patients usually have elevated serum IL-10 levels, the scientists also looked at IRAK1 levels in
blood from atherosclerosis patients. They found that IRAK1 is modified and localized to the nucleus in these patients,
indicating a possible link between IRAK1 regulation and the pathogenesis of atherosclerosis.
"Inflammation and infection have been increasingly shown to play a significant role in the pathogenesis and/or resolution of
atherosclerosis," explains Dr. Li. "Anti- inflammatory cytokines such as IL-10 may serve as a self protective mechanism to
prevent excessive inflammation and contribute to plaque stability. Indeed, patients with higher IL-10 serum levels have a
better chance of recovery. Therefore, elevated IRAK1 modification and IL-10 levels observed in atherosclerosis patients may
be a compensatory and self-protective mechanism."
Manipulating innate immunity may eventually be a therapeutic strategy for treating atherosclerosis. "Our study, as well as
others, indicates that innate immunity alteration plays a critical role in either the pathogenesis or resolution of
atherosclerosis. IRAK1 may provide a viable target for developing therapeutic interventions for atherosclerosis. Compounds or
strategies directed at preventing or enhancing IRAK1 modification and nuclear entry may hold great promise in treating
atherosclerosis," concludes Dr. Li.
Besides atherosclerosis, alterations in innate immunity can cause diabetes, cancer, and numerous other inflammatory
disorders. Further understanding of the innate immunity process may lead to development of therapies for these diseases as
well.
The Journal of Biological Chemistry's Papers of the Week is an online feature which highlights the top one percent of papers
received by the journal. Brief summaries of the papers and explanations of why they were selected for this honor can be
accessed directly from the home page of the Journal of Biological Chemistry online at jbc.
The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization
with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and
universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for
Experimental Biology. The Society's primary purpose is to advance the sciences of biochemistry and molecular biology through
its publications, the Journal of Biological Chemistry, The Journal of Lipid Research, Molecular and Cellular Proteomics, and
Biochemistry and Molecular Biology Education, and the holding of scientific meetings.
For more information about ASBMB, see the Society's website at asbmb.
Contact: Nicole Kresge
nkresgeasbmb
301-634-7415
American Society for Biochemistry and Molecular Biology
Blueprint Develops ProteoGlyphs: a Visual Language to Describe Biomolecular Structure
Every day, humans use symbols to communicate
complex information. In a written language, curved lines form letters,
which can be combined into constructs that represent spoken sounds.
Similarly, in modern biology, ontology and structure initiatives have
converted lengthy descriptions of biomolecular function and form into
information-dense whorls and lines that can be strung together to
describe the complexity of a cell.
Leading this charge, The Blueprint Initiative Asia Pte. Ltd. today
released a new biomolecular language-ProteoGlyphs-that describes
conserved protein domains and provides researchers with visual clues to
the structure of proteins involved in myriad metabolic pathways. Because
structure plays such a vital role in protein function, the new tool
offers scientists a better understanding of how these pathways work.
This knowledge is critical to understanding human disease and how to
treat it.
Randall C Willis
Tel: 416-596-6266
e-Mail: rwillisblueprint
blueprint
complex information. In a written language, curved lines form letters,
which can be combined into constructs that represent spoken sounds.
Similarly, in modern biology, ontology and structure initiatives have
converted lengthy descriptions of biomolecular function and form into
information-dense whorls and lines that can be strung together to
describe the complexity of a cell.
Leading this charge, The Blueprint Initiative Asia Pte. Ltd. today
released a new biomolecular language-ProteoGlyphs-that describes
conserved protein domains and provides researchers with visual clues to
the structure of proteins involved in myriad metabolic pathways. Because
structure plays such a vital role in protein function, the new tool
offers scientists a better understanding of how these pathways work.
This knowledge is critical to understanding human disease and how to
treat it.
Randall C Willis
Tel: 416-596-6266
e-Mail: rwillisblueprint
blueprint
Leading Health Organizations Launch New Accreditation Process For Laboratories Across Africa
Government health officials from 13 African countries today launched the first-ever push for accreditation of the continent's medical laboratories, starting a process that the World Health Organization (WHO) and the U.S. Government believe will be an historic step to strengthen health systems and lead to better care for patients.
Just a handful of Africa's laboratories are now accredited, in part because the existing international accreditation process is so time-consuming. Many laboratories lack equipment, proper funding, adequate training for lab workers, and systematic management of work. This new effort will operate under the guidance of the WHO Regional Office for Africa (WHO/AFRO) and the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), implemented through the U.S. Department of Health and Human Services/Centers for Disease Control and Prevention (HHS/CDC). The American Society for Clinical Pathology (ASCP) will assign dozens of volunteer American lab professionals and the Clinton HIV/AIDS Initiative will help implement action-oriented training programs to boost and standardize the quality of African laboratories.
WHO-AFRO has established a five-step accreditation process structured around its core standards for laboratories, which will allow labs to gradually receive credit for improvement - and eventually attain accreditation. For many laboratories that employ top-notch workers, this extra help is seen as critical to reach a consistent high standard of work.
"It's time for Africa to go in this direction - accreditation is the only way to be sure a laboratory is a good laboratory," said Agnes Binagwaho, Rwanda's Permanent Secretary in the Ministry of Health. "We cannot provide high quality care - no matter what type of disease we're fighting - without strong laboratories. This will greatly strengthen our health systems in the short term and long term. This is all about building sustainable health systems."
Laboratories form the backbone of health systems around the world, providing doctors and other health care workers with results of a battery of tests for deadly diseases. Sub-Saharan Africa carries a huge burden of disease - it is estimated that the continent has more than 2 million deaths annually from AIDS, nearly 2 million deaths from tuberculosis, and roughly 1 million deaths from malaria - and yet its laboratories are among the most ill-equipped and poorly resourced facilities anywhere.
If laboratories function properly, doctors and nurses will not only get correct diagnoses of diseases and an indication of when and how to begin treatment, but they will also know when drugs fail and when people develop resistance to medications. This is a critical component of monitoring patients infected with HIV, tuberculosis, and malaria, as well as a host of other diseases. In addition, an efficient laboratory can dramatically reduce waiting time to get results - allowing patients in parts of Africa who often travel a day or more for testing to receive the laboratory results sooner. Studies have shown that when patients need to return for a second visit to a hospital or clinic for test results, significant percentages fail to do so.
The work to improve laboratories began to gain momentum nearly a decade ago; the intensified fight against HIV/AIDS represented by PEPFAR and others provided funding and demand to improve laboratory services. Two of the integral partners in this process have been the WHO-AFRO and PEPFAR through HHS/CDC.
"Supporting governments' efforts to strengthen national health care systems, including laboratory quality management, is essential to ensuring sustainability of country-driven HIV/AIDS interventions," said Ambassador Eric Goosby, U.S. Global AIDS Coordinator. "Efforts like this new lab accreditation process are essential to equipping countries and communities with the tools necessary for progress on health."
El-hadj Belabbes, HIV Lab Officer for the WHO Inter-country Support Team, Central Africa, said the outcome is the result of efforts initiated by WHO-AFRO and HHS/CDC eight years ago, leading to meetings with partners in Zimbabwe, Ghana, South Africa, Ethiopia, and Senegal.
"Following these meetings, WHO-AFRO, in collaboration with its partners, has initiated the first phase of laboratory accreditation but also has started the implementation of comprehensive Quality Management Systems and laboratory management training," Belabbes said.
At the Kigali meeting, which runs from July 27 to 29, participants include 120 experts and policymakers from Rwanda, Botswana, Cameroon, Cote d'Ivoire, Ethiopia, Kenya, Malawi, Nigeria, Senegal, Tanzania, Ghana, Uganda, and Zambia. The meeting will have three goals: unveil a blueprint toward the path of accreditation; obtain key stakeholders' support for accreditation; and showcase a task-based training program in support of laboratory improvement required for accreditation.
"This is a tremendous leap forward for diagnostic laboratory services in Africa," said Dr. Lee H. Hilborne, past president of the American Society for Clinical Pathology, which helped design the training program and will send volunteers from U.S. laboratories to assist the training. "The commitment of laboratories, Ministries of Health, and international partners, including ASCP, speaks to the realization that investments in infrastructure to date have matured to the point where it is now possible to explicitly commit to having Africa's laboratories aspire to and achieve compliance with international standards. The people of Africa and the world will benefit from this essential step forward."
"Every patient deserves "access to accurate and reliable diagnostics that meaningfully inform the care and treatment they receive. The laboratory accreditation process is an important means to encourage, evaluate and recognize competence, quality and reliability in medical laboratory testing. We consider laboratories to be a gateway to the management and treatment of priority diseases," said Philip Rotz, Training Coordinator of the Laboratory Services Team for the Clinton HIV/AIDS Initiative.
Connie Wilkins, a hospital laboratory director in Joplin, Missouri, in the United States and one of ASCP's volunteers, said that the process will be critically important in helping laboratories run more efficiently. Much of the effort will be focused on training laboratory managers and other administrative staff to improve the management of the facilities. After the laboratories go through the five-stage process for WHO-AFRO, they will be closer to applying for international accreditation as well.
"Anything we can do in education, including in improving laboratories is not just about saving a life but about improving quality of life," Wilkins said. "We're improving healthcare starting with being able to deliver to doctors a more accurate diagnosis of the problem and by allowing doctors to see how well treatments are working through periodic testing. It's just a huge deal."
Source:
Preeti Singh
Burness Communications
Just a handful of Africa's laboratories are now accredited, in part because the existing international accreditation process is so time-consuming. Many laboratories lack equipment, proper funding, adequate training for lab workers, and systematic management of work. This new effort will operate under the guidance of the WHO Regional Office for Africa (WHO/AFRO) and the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), implemented through the U.S. Department of Health and Human Services/Centers for Disease Control and Prevention (HHS/CDC). The American Society for Clinical Pathology (ASCP) will assign dozens of volunteer American lab professionals and the Clinton HIV/AIDS Initiative will help implement action-oriented training programs to boost and standardize the quality of African laboratories.
WHO-AFRO has established a five-step accreditation process structured around its core standards for laboratories, which will allow labs to gradually receive credit for improvement - and eventually attain accreditation. For many laboratories that employ top-notch workers, this extra help is seen as critical to reach a consistent high standard of work.
"It's time for Africa to go in this direction - accreditation is the only way to be sure a laboratory is a good laboratory," said Agnes Binagwaho, Rwanda's Permanent Secretary in the Ministry of Health. "We cannot provide high quality care - no matter what type of disease we're fighting - without strong laboratories. This will greatly strengthen our health systems in the short term and long term. This is all about building sustainable health systems."
Laboratories form the backbone of health systems around the world, providing doctors and other health care workers with results of a battery of tests for deadly diseases. Sub-Saharan Africa carries a huge burden of disease - it is estimated that the continent has more than 2 million deaths annually from AIDS, nearly 2 million deaths from tuberculosis, and roughly 1 million deaths from malaria - and yet its laboratories are among the most ill-equipped and poorly resourced facilities anywhere.
If laboratories function properly, doctors and nurses will not only get correct diagnoses of diseases and an indication of when and how to begin treatment, but they will also know when drugs fail and when people develop resistance to medications. This is a critical component of monitoring patients infected with HIV, tuberculosis, and malaria, as well as a host of other diseases. In addition, an efficient laboratory can dramatically reduce waiting time to get results - allowing patients in parts of Africa who often travel a day or more for testing to receive the laboratory results sooner. Studies have shown that when patients need to return for a second visit to a hospital or clinic for test results, significant percentages fail to do so.
The work to improve laboratories began to gain momentum nearly a decade ago; the intensified fight against HIV/AIDS represented by PEPFAR and others provided funding and demand to improve laboratory services. Two of the integral partners in this process have been the WHO-AFRO and PEPFAR through HHS/CDC.
"Supporting governments' efforts to strengthen national health care systems, including laboratory quality management, is essential to ensuring sustainability of country-driven HIV/AIDS interventions," said Ambassador Eric Goosby, U.S. Global AIDS Coordinator. "Efforts like this new lab accreditation process are essential to equipping countries and communities with the tools necessary for progress on health."
El-hadj Belabbes, HIV Lab Officer for the WHO Inter-country Support Team, Central Africa, said the outcome is the result of efforts initiated by WHO-AFRO and HHS/CDC eight years ago, leading to meetings with partners in Zimbabwe, Ghana, South Africa, Ethiopia, and Senegal.
"Following these meetings, WHO-AFRO, in collaboration with its partners, has initiated the first phase of laboratory accreditation but also has started the implementation of comprehensive Quality Management Systems and laboratory management training," Belabbes said.
At the Kigali meeting, which runs from July 27 to 29, participants include 120 experts and policymakers from Rwanda, Botswana, Cameroon, Cote d'Ivoire, Ethiopia, Kenya, Malawi, Nigeria, Senegal, Tanzania, Ghana, Uganda, and Zambia. The meeting will have three goals: unveil a blueprint toward the path of accreditation; obtain key stakeholders' support for accreditation; and showcase a task-based training program in support of laboratory improvement required for accreditation.
"This is a tremendous leap forward for diagnostic laboratory services in Africa," said Dr. Lee H. Hilborne, past president of the American Society for Clinical Pathology, which helped design the training program and will send volunteers from U.S. laboratories to assist the training. "The commitment of laboratories, Ministries of Health, and international partners, including ASCP, speaks to the realization that investments in infrastructure to date have matured to the point where it is now possible to explicitly commit to having Africa's laboratories aspire to and achieve compliance with international standards. The people of Africa and the world will benefit from this essential step forward."
"Every patient deserves "access to accurate and reliable diagnostics that meaningfully inform the care and treatment they receive. The laboratory accreditation process is an important means to encourage, evaluate and recognize competence, quality and reliability in medical laboratory testing. We consider laboratories to be a gateway to the management and treatment of priority diseases," said Philip Rotz, Training Coordinator of the Laboratory Services Team for the Clinton HIV/AIDS Initiative.
Connie Wilkins, a hospital laboratory director in Joplin, Missouri, in the United States and one of ASCP's volunteers, said that the process will be critically important in helping laboratories run more efficiently. Much of the effort will be focused on training laboratory managers and other administrative staff to improve the management of the facilities. After the laboratories go through the five-stage process for WHO-AFRO, they will be closer to applying for international accreditation as well.
"Anything we can do in education, including in improving laboratories is not just about saving a life but about improving quality of life," Wilkins said. "We're improving healthcare starting with being able to deliver to doctors a more accurate diagnosis of the problem and by allowing doctors to see how well treatments are working through periodic testing. It's just a huge deal."
Source:
Preeti Singh
Burness Communications
Researchers Make New Finding About How Memory Is Stored
Researchers at Wake Forest University School of Medicine are the first to show that the location of protein-destroying "machines" in nerve cells in the brain may play an important role in how memories are formed a finding with potential implications for treating Alzheimer's and other brain diseases. The research is published in the current issue of Learning & Memory.
"We hope to exploit this finding to manipulate memory and find ways to make it better," said Ashok Hegde, Ph.D., associate professor of neurolobiology and anatomy. "Our goal is to develop a new strategy for treating memory loss."
In mice, the researchers studied nerve cells in the hippocampus, a region of the brain associated with memory coding and storing of memory. Scientists know that the synapses, or connections between nerve cells, play an important role in memory. Each nerve cell in the brain connects with at least a thousand other nerve cells.
"When humans or animals learn and store what is learned in their memory, these connections between cells become stronger or weaker," said Hegde. "For example, if we learn to do something better, such as playing softball, the synapses that control our hand-eye coordination will become stronger. If we learn to ignore something, such as the barking of a neighbor's dog, then the synapses that control paying attention will become weaker."
In mice, scientists are able to determine the strength of these connections, and they studied how protein degradation affects connection strength. It is known that the degradation of proteins, which are made by cells to control cell functions, plays an important role in memory function.
Levels of proteins are controlled by cylinder-shaped protein-destroying machines known as proteasomes that are located throughout all cell types. The Wake Forest researchers are the first to show that the proteasomes in different parts of nerve cells plays different roles in controlling synapse strength and presumably in memory. They made this discovery by studying connection strength with and without a chemical that blocks activity of the proteasomes.
They found that proteasomes located in the dendrites, the branched projections of a neuron that act to conduct the electrical stimulation, limit the strength of the connections between cells. Proteasomes in the nucleus, the part of the cell that contains genetic material, help maintain synapse strength for long periods of time.
Their next goal is to learn to block proteasome activity specifically in the dendrites to increase the strength of synapses and of memory. They are currently conducting studies in mice to block proteasome activity in the dendrites, using mazes to test memory.
"If we see a memory enhancement when we block the proteasome in dendrites, we can use this strategy to treat memory loss," said Hegde.
He said the research is important because it has implications for treating human diseases that affect memory.
"Protein degradation is abnormal in many brain diseases, including Alzheimer's," said Hegde. "Having a thorough knowledge of how protein degradation works to changes synapses is a first step to finding a cure for memory loss."
The research was funded by the National Institutes of Health.
Co-researchers were Chenghai Dong, M.D., Ph.D., Sudarshan Upadhya, Ph.D., Lan Ding, Ph.D., and Thuy Smith, M.S., all with Wake Forest.
Wake Forest University Baptist Medical Center (wfubmc) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Wake Forest University Baptist Medical Center
Medical Center Blvd.
Winston-Salem, NC 27157-1015
United States
www1.wfubmc
"We hope to exploit this finding to manipulate memory and find ways to make it better," said Ashok Hegde, Ph.D., associate professor of neurolobiology and anatomy. "Our goal is to develop a new strategy for treating memory loss."
In mice, the researchers studied nerve cells in the hippocampus, a region of the brain associated with memory coding and storing of memory. Scientists know that the synapses, or connections between nerve cells, play an important role in memory. Each nerve cell in the brain connects with at least a thousand other nerve cells.
"When humans or animals learn and store what is learned in their memory, these connections between cells become stronger or weaker," said Hegde. "For example, if we learn to do something better, such as playing softball, the synapses that control our hand-eye coordination will become stronger. If we learn to ignore something, such as the barking of a neighbor's dog, then the synapses that control paying attention will become weaker."
In mice, scientists are able to determine the strength of these connections, and they studied how protein degradation affects connection strength. It is known that the degradation of proteins, which are made by cells to control cell functions, plays an important role in memory function.
Levels of proteins are controlled by cylinder-shaped protein-destroying machines known as proteasomes that are located throughout all cell types. The Wake Forest researchers are the first to show that the proteasomes in different parts of nerve cells plays different roles in controlling synapse strength and presumably in memory. They made this discovery by studying connection strength with and without a chemical that blocks activity of the proteasomes.
They found that proteasomes located in the dendrites, the branched projections of a neuron that act to conduct the electrical stimulation, limit the strength of the connections between cells. Proteasomes in the nucleus, the part of the cell that contains genetic material, help maintain synapse strength for long periods of time.
Their next goal is to learn to block proteasome activity specifically in the dendrites to increase the strength of synapses and of memory. They are currently conducting studies in mice to block proteasome activity in the dendrites, using mazes to test memory.
"If we see a memory enhancement when we block the proteasome in dendrites, we can use this strategy to treat memory loss," said Hegde.
He said the research is important because it has implications for treating human diseases that affect memory.
"Protein degradation is abnormal in many brain diseases, including Alzheimer's," said Hegde. "Having a thorough knowledge of how protein degradation works to changes synapses is a first step to finding a cure for memory loss."
The research was funded by the National Institutes of Health.
Co-researchers were Chenghai Dong, M.D., Ph.D., Sudarshan Upadhya, Ph.D., Lan Ding, Ph.D., and Thuy Smith, M.S., all with Wake Forest.
Wake Forest University Baptist Medical Center (wfubmc) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Wake Forest University Baptist Medical Center
Medical Center Blvd.
Winston-Salem, NC 27157-1015
United States
www1.wfubmc
Avian Flu 'Supermap' Yields New Info On Source/spread
Scientists here have designed a new, interactive map of the spread of the avian flu virus (H5N1) that for the first time incorporates genetic, geographic and evolutionary information that may help predict where the next outbreak of the virus is likely to occur.
In the process, they also tested hypotheses about the nature of specific strains of the virus that appear to be heading westward and have the ability to infect humans.
A team of biomedical experts, led by Daniel Janies, an assistant professor in the department of biomedical informatics, used special software to create an evolutionary tree of the virus's mutations. They used Keyhole Markup Language in Google Earth to project the tree onto the globe and then chose colors and symbols to indicate different hosts that carry the virus and where they live. TimeSpan, another function in Google Earth, allowed them to animate the spread of the virus over the past decade.
The map is chock-full of additional information. Clicking on a specific viral subtype generates a popup window revealing diagnostic mutations that distinguish one strain of the virus from another, and all of the data is linked to the National Institute of Health's GenBank.
"The map gives us a whole new way of seeing the virus in action and understanding what it is - and isn't - doing," says Janies. "It's enabled us to compare findings about viruses in the real world against pre-existing hypotheses about the spread of H5N1 that come from laboratory studies."
The study appears online in Systematic Biology.
The avian flu virus was first recognized in wild aquatic birds in Guangdong, China in 1996. It then spread to chickens and humans in Hong Kong the following year. From 1997 until 2005, it emerged in several Southeast Asian countries and spread via multiple hosts throughout central and southern China, Russia, the Middle East and India. To date, additional outbreaks have been reported as far west as Europe and Africa and as far east as Japan, Korea and Indonesia.
In creating the supermap, researchers studied genetic data from 351 isolates of the virus. They were especially interested in discovering if certain hosts were carrying specific forms of the virus and which viruses carried specific mutations enabling transmission to humans.
"We found the visualization of multiple layers of information very helpful in generating hypotheses we could test through statistical analysis of the mutation data we organized in the evolutionary tree," says Janies. "The findings helped us understand whether mutations that appear to be associated with certain hosts or geographic regions appeared by chance, or whether they were true adaptations of the virus as it spread."
Flu viruses are classified according to several criteria: whether they come from animals or humans, and the activity of two key proteins that sit on the surface of the virus, hemaglutinin (HA), and neuraminidase (NA). HA helps the virus "stick" to a host cell and infect it; NA helps the virus escape from the cell and spread to other cells and hosts. In the past, scientists hypothesized that if a strain of the virus emerged that enabled human-to-human transmission, it would probably involve mutations in these two proteins.
Janies and his colleagues did not find any genotypes associated with mutations in these two surface proteins that were significantly associated with any specific type of host. They did, however, find a strong association between a specific genotype (Lysine-627 in the polymerase basic protein of the virus) and mammalian hosts in the field.
"While this genotype is not exclusive to mammals, we think it is important to track how this particular mutation is spreading because it appears to be so infective and deadly in mice," says Janies.
For now, it appears that the H5N1 virus is not highly communicable to humans or between humans. But that could change quickly. Scientists say emerging, unpredictable mutations could equip the virus with just what it needs to jump more nimbly between species, and experts say a pandemic would be disastrous. The Centers for Disease Control and Prevention estimates that 15 to 35 percent of the human population in the United States could become infected at a cost ranging from $71 billion to $166 billion.
According to the World Health Organization, which is charged with tracing H5N1 data, there have been 291 cases of the disease in humans since the initial outbreak, and 172 deaths.
Janies says the supermap is universally applicable in tracking the spread of infectious agents, adding that his group is already working on mapping other diseases, such as SARS. He notes that despite recent efforts to stimulate collaboration and publication of all data regarding the H5N1 virus, a significant amount of genomic information remains in private hands. That, alone, means the current map is incomplete, at best. He also notes that while there is good data in a number of public databases, those genetic sequences are not well-annotated with information about host species - whether they are wild or domestic, for example.
Still, the supermap may offer investigators a novel way to share information about new outbreaks and predict where public health officials need to act quickly to begin countermeasures. "There was an interesting case in 2004, where some infected eagles were illegally smuggled from Thailand to Belgium," says Janies. "While the birds were quickly confined and the virus didn't spread at that point, those cases did show up as a clear anomaly in our map, reflecting an instance where illegal trade allowed the virus to make a huge geographic leap."
The project involved a highly trained mix of experts in physics, biology, geography and information systems to manage the complexity of the data involved. Co-authors include Habib Farhat, from OSU's department of physics; Andrew Hill and Robert Guralnick, from the University of Colorado; and Eric Waltari and Ward Wheeler, from the American Museum of Natural History.
Funding for the project came from the National Institutes of Health and the Defense Advanced Research Projects Agency.
Contact: Michelle Gailiun
Ohio State University
In the process, they also tested hypotheses about the nature of specific strains of the virus that appear to be heading westward and have the ability to infect humans.
A team of biomedical experts, led by Daniel Janies, an assistant professor in the department of biomedical informatics, used special software to create an evolutionary tree of the virus's mutations. They used Keyhole Markup Language in Google Earth to project the tree onto the globe and then chose colors and symbols to indicate different hosts that carry the virus and where they live. TimeSpan, another function in Google Earth, allowed them to animate the spread of the virus over the past decade.
The map is chock-full of additional information. Clicking on a specific viral subtype generates a popup window revealing diagnostic mutations that distinguish one strain of the virus from another, and all of the data is linked to the National Institute of Health's GenBank.
"The map gives us a whole new way of seeing the virus in action and understanding what it is - and isn't - doing," says Janies. "It's enabled us to compare findings about viruses in the real world against pre-existing hypotheses about the spread of H5N1 that come from laboratory studies."
The study appears online in Systematic Biology.
The avian flu virus was first recognized in wild aquatic birds in Guangdong, China in 1996. It then spread to chickens and humans in Hong Kong the following year. From 1997 until 2005, it emerged in several Southeast Asian countries and spread via multiple hosts throughout central and southern China, Russia, the Middle East and India. To date, additional outbreaks have been reported as far west as Europe and Africa and as far east as Japan, Korea and Indonesia.
In creating the supermap, researchers studied genetic data from 351 isolates of the virus. They were especially interested in discovering if certain hosts were carrying specific forms of the virus and which viruses carried specific mutations enabling transmission to humans.
"We found the visualization of multiple layers of information very helpful in generating hypotheses we could test through statistical analysis of the mutation data we organized in the evolutionary tree," says Janies. "The findings helped us understand whether mutations that appear to be associated with certain hosts or geographic regions appeared by chance, or whether they were true adaptations of the virus as it spread."
Flu viruses are classified according to several criteria: whether they come from animals or humans, and the activity of two key proteins that sit on the surface of the virus, hemaglutinin (HA), and neuraminidase (NA). HA helps the virus "stick" to a host cell and infect it; NA helps the virus escape from the cell and spread to other cells and hosts. In the past, scientists hypothesized that if a strain of the virus emerged that enabled human-to-human transmission, it would probably involve mutations in these two proteins.
Janies and his colleagues did not find any genotypes associated with mutations in these two surface proteins that were significantly associated with any specific type of host. They did, however, find a strong association between a specific genotype (Lysine-627 in the polymerase basic protein of the virus) and mammalian hosts in the field.
"While this genotype is not exclusive to mammals, we think it is important to track how this particular mutation is spreading because it appears to be so infective and deadly in mice," says Janies.
For now, it appears that the H5N1 virus is not highly communicable to humans or between humans. But that could change quickly. Scientists say emerging, unpredictable mutations could equip the virus with just what it needs to jump more nimbly between species, and experts say a pandemic would be disastrous. The Centers for Disease Control and Prevention estimates that 15 to 35 percent of the human population in the United States could become infected at a cost ranging from $71 billion to $166 billion.
According to the World Health Organization, which is charged with tracing H5N1 data, there have been 291 cases of the disease in humans since the initial outbreak, and 172 deaths.
Janies says the supermap is universally applicable in tracking the spread of infectious agents, adding that his group is already working on mapping other diseases, such as SARS. He notes that despite recent efforts to stimulate collaboration and publication of all data regarding the H5N1 virus, a significant amount of genomic information remains in private hands. That, alone, means the current map is incomplete, at best. He also notes that while there is good data in a number of public databases, those genetic sequences are not well-annotated with information about host species - whether they are wild or domestic, for example.
Still, the supermap may offer investigators a novel way to share information about new outbreaks and predict where public health officials need to act quickly to begin countermeasures. "There was an interesting case in 2004, where some infected eagles were illegally smuggled from Thailand to Belgium," says Janies. "While the birds were quickly confined and the virus didn't spread at that point, those cases did show up as a clear anomaly in our map, reflecting an instance where illegal trade allowed the virus to make a huge geographic leap."
The project involved a highly trained mix of experts in physics, biology, geography and information systems to manage the complexity of the data involved. Co-authors include Habib Farhat, from OSU's department of physics; Andrew Hill and Robert Guralnick, from the University of Colorado; and Eric Waltari and Ward Wheeler, from the American Museum of Natural History.
Funding for the project came from the National Institutes of Health and the Defense Advanced Research Projects Agency.
Contact: Michelle Gailiun
Ohio State University
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