EU Grants 2.5 Million Euros For Research On Childhood Gut Infections In Latin America

Diarrhoea due to gut infections is a world-wide problem causing about 12,500 deaths/day in children less than 5 years old. Our knowledge about bacterial and parasitic infections causing diarrhoea is limited. Tools for diagnosis and surveillance of many gut infections are inadequate. Leading experts from four European countries and five Latin American countries have teamed up to investigate the effects of gut infections on growth and development in young children. The four year project called “CONTENT” starting on October 1st 2006 is supported by a 2.5 Million Euro research grant from the European Commission’s Framework 6 International Cooperation programme.

One of the first infections acquired in infancy is the stomach bacterium Helicobacter pylori. This infection, which is generally life-long, is a risk factor for developing gastric cancer in adults. Initial infection with H. pylori reduces the amount of acid in the stomach. Acid secretion in the stomach is an important defence mechanism against multiple gut infections which cause diarrhoeal diseases. The CONTENT consortium is investigating the effects of H. pylori on the incidence of diarrhoeal disease, childhood growth and iron deficiency anaemia in Latin American children. The team is also developing new diagnostic tests for gut infections. Latin American partners from Argentina, Brazil, Chile, Mexico and Peru are involved in the project. European partners are based in Holland, Ireland, Portugal and the United Kingdom.

The project is being co-ordinated by partners at the University of Leeds in the United Kingdom and Trinity College Dublin in Ireland. The knowledge acquired by the CONTENT consortium will help develop new prevention methods and diagnostic tools for gut infections. The CONTENT consortium will collaborate with public health organisations throughout Latin America to spread information arising from the project and to raise awareness and education on childhood gut infections and diarrhoeal diseases.

For further information on CONTENT project contact Dr. J. Crabtree

Contact: Hannah Love

University of Leeds

UNICEF Responds To Millions Affected By Floods In India And Nepal With Life-Saving Supplies

Severe floods have destroyed almost a quarter of a million homes affecting at least 1.4 million people in northern part of the state of Bihar in India. More than 70,000 people have been displaced in Nepal. Children are the most vulnerable to disease and the distress of displacement, says UNICEF.

UNICEF is responding to the worst floods in 50 years in Bihar with clean water, shelter and medicines as families crowd into relief camps in one of India’s poorest states.

The flooding started after the Kosi River broke a dam in Nepal and breached mud embankments in the Bihar state in India a week ago. The displaced families will not be able to return to their homes for another couple of months until the embankment is repaired.

“At a time like this, it matters little how the floods started or who or what is at fault. What is critical is urgent help to those in need. These are the some of the worst floods in generations and they present a huge challenge for governments and humanitarian organisations,” said UNICEF’s Regional Director for South Asia, Daniel Toole. “UNICEF’s priority is to deliver life-saving supplies and to ensure that children and women – the most vulnerable to disease and distress — receive medicines, clean drinking water, access to sanitation and, with governments and partners, enough food. Even at the best of times, South Asia has many of the poorest people in the world. These massive floods can wash away even the most basic hope that families have.”


Over 1,000 villages in 13 districts of north Bihar have been affected, causing large-scale displacement. The government in India expects that up to two million people will be affected. The official death toll is 55, although this figure is rising.

The floods have caused extensive damage and disruption to roads, water, and electricity supplies in the affected areas. Essential commodities, including food, are now being transported by boat.

UNICEF is concerned that the floods will severely impact women and children already vulnerable in one of India’s poorest states. A major concern is that as the number of displaced people in relief camps increases, so does the risk of communicable diseases. Hygiene conditions in the camps are poor: there is an insufficient amount of hand pumps for clean drinking water and of toilets, resulting in open defecation, an extremely dangerous practice as it facilitates the spread of disease.

Displaced children, pregnant and lactating women, as well as the elderly face additional challenges due to the extremely hot weather. The heat, combined with limited supplies of safe drinking water and poor hygiene conditions, poses a great risk of water and vector-borne diseases. Cases of fever and diarrhoea have already been reported.


In south eastern Nepal, the flooding has caused significant damages and human suffering in Sunsari and Saptari district, displacing at least 70,000 people. In addition, over 5,000 people from Bihar have crossed into Nepal to seek relief from the floods. Many of the displaced are sheltering in schools, and around 30 per cent of those are children.

The immediate needs of the affected populations are water supply and hygiene materials, food – including special foods for babies as well as pregnant and lactating women – and shelter.

UNICEF response

In India, UNICEF has conducted a rapid assessment of the situation in three of the worst affected districts, and has provided essential supplies to some 8,000 families. Working with local government and partners, UNICEF has provided tarpaulin sheets, jerry cans, hygiene kits, water purification tablets, 60 life-jackets, 400,000 halogen tablets, 25,000 kilograms of bleaching powder and 30,000 oral rehydration salt packets. UNICEF continues to work with local government and NGO partners to meet the needs of the most vulnerable children and women affected by the floods.

In Nepal, UNICEF has already provided relief items to over 10,000 people in temporary settlements and is seeking to reach 55,000 affected people in total. So far, UNICEF has delivered in collaboration with other humanitarian actors and government agencies: 500 blankets, 100 plastic sheets, 2,112 tarpaulins, 13,200 sachets of oral rehydration salt, 8,000 insecticide bed nets, 4,869 sets of hygiene kits, 20 first aid kits, 325 kitchen utensils, 90 sets of school kits. UNICEF has also distributed 312,000 water purifying tablets, 5,500 buckets, 3,700 mugs, and 585 bottles of water purification solution. UNICEF is collaborating with other organizations to install 20 hand pumps, 760 latrines, 60 garbage pits, and 320 bathing spaces, especially for women and adolescent girls, and will provide support to install temporary latrines in all shelter sites.


Tuberculosis Still A Serious Public Health Threat, Say Indiana State Health Officials

Tuberculosis (TB) is one of the most common and deadliest diseases, killing millions worldwide. Tuesday, March 24 is World TB Day, and state health officials are taking the opportunity to remind the public TB is still a serious health threat.

“While the overall number of new TB cases in Indiana has dropped in the last year, certain counties are seeing significant numbers of new cases,” says Loren Robertson, assistant commissioner, Public Health and Preparedness Commission at the Indiana State Department of Health. “It is a reminder we must continue our efforts and dedication to eliminating the threat of TB for all Hoosiers.”

In 2008, there were 118 active cases and nine TB-related deaths in Indiana, with 50 percent of the state’s cases in the three most populated counties: Allen, Lake and Marion. In 2007 there were 129 active TB cases in the state.

On March 24, 1882, German physician Robert Koch discovered the bacteria causing TB. More than 100 years later, state health officials say TB is not a disease of the past, nor does it only affect impoverished countries.

“TB remains one of the leading causes of death among infectious diseases worldwide, even though it is readily treatable and preventable,” says Robertson. “Counties, states, and nations need to work together to eliminate TB. That is why the theme of this year’s World TB Day is ‘Partnerships for TB Elimination.’”

TB is spread through the air from person to person when someone with the disease coughs or sneezes. People nearby may breathe in these bacteria and become infected. Antibiotics are available that can cure TB disease and prevent latent TB infection from developing into an active disease. Health officials say ensuring patients with the active TB disease complete treatment is a vital aspect of TB control.

An estimated two billion people worldwide are infected with the bacteria that cause TB, although most people with latent TB infection never develop the disease. In these people, the TB bacteria can remain dormant for a lifetime without causing problems. However in others, especially those with weak immune systems, the bacteria can become active and cause TB anywhere in the body.

“Although evidence suggests the nation is progressing towards elimination, many challenges remain, particularly the increasing impact of the global TB epidemic on the United States, the continued threat of multi-drug resistant TB, and the interaction between HIV infection and TB,” says Robertson.

Indiana Dept of Health

NIAMS Funds New Centers Of Research Translation

NIAMS Funds New Centers of Research Translation Bridging the gap between bench and bedside is the goal of four new Centers of Research Translation (CORTs) funded by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health (NIH). CORTs are designed to bring together basic and clinical research in a way that helps translate basic discoveries into new drugs, treatments and diagnostics.

The four new centers are:

Center for Translating Molecular Signal Pathways to Orthopaedic Trauma Care, headed by Randy Rosier, M.D., Ph.D., chair of orthopaedics at the University of Rochester, N.Y. This center will study the biological basis of fracture healing and the efficacy of a potential new treatment, teriparatide, an injectable form of human parathyroid hormone that stimulates new bone formation.

Center for Lupus Research, headed by M. Virginia Pascual, M.D., at the Baylor Research Institute in Dallas, Texas. This CORT will study the role of different cell types in the origin and development of lupus, will develop markers of disease activity and severity, and will look for new targets for treatment. Lupus is an autoimmune disease that can affect many parts of the body, including the joints, skin, kidneys, lungs, heart and/or brain.

Center for X-Linked Hypophosphatemic Rickets Research, led by Thomas O. Carpenter, M.D., at Yale University in New Haven, Conn. This center will study the various molecular contributors to this genetic form of rickets and work toward developing new treatments.

Center for Research Translation in Scleroderma, headed by Frank Arnett, M.D., professor of internal medicine in the Division of Rheumatology at the University of Texas Medical School at Houston. This center will study the molecular basis of scleroderma to understand its underlying causes using functional genomics and gene networks. Studies will involve a multiethnic cohort of scleroderma patients, as well as two mouse models of fibrosis recently developed at this center. Scleroderma involves the abnormal growth of connective tissue, which supports the skin and internal organs.

CORT grants are a new funding mechanism for NIAMS, and require centers to encompass at least three projects, including one clinical and one basic research study.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, visit the NIAMS Web site at niams.nih/.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.

Contact: Ray Fleming

NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

GlaxoSmithKline And Theravance Announce Start Of Large Phase 2B ICS And LABA Studies For Asthma In The Horizon Programme

GlaxoSmithKline Plc (GSK) and Theravance, Inc. (NASDAQ: THRX) announced the start of large Phase 2b asthma dose-optimisation studies with both the lead inhaled corticosteroid (ICS) GW685698 (’698) and the lead long-acting beta agonist (LABA) GW642444 (’444) assets in the ‘Horizon’ programme to develop a next-generation combination product.

GSK began enrolling patients with mild to severe asthma in the ’698 Phase 2b clinical programme on 21st December 2007and began enrolling patients with persistent asthma in the ’444 Phase 2b clinical programme on 29th December 2007. These clinical programmes will determine the most effective doses to be taken into Phase 3 combination studies. The Phase 2b COPD programme with ’444 is also on schedule to commence in 1H 2008.

Darrell Baker, SVP GSK Respiratory Medicines Development Centre said, “The programme is progressing well and we are delighted to have two very strong assets to progress into our large Phase 2b studies.” He continued, “We have seen encouraging results in previous studies and have confidence in our ongoing programme. Both asthma and COPD are serious, debilitating diseases where there remains a considerable unmet need. We believe through this programme we will introduce a meaningful option for the treatment of patients with these conditions.”

“We are very pleased to have met the important milestone of initiating the larger Phase 2b studies with the lead compound ’444 and with the progress of ’698,” said Rick E Winningham, Chief Executive Officer at Theravance. “Based upon recent clinical and preclinical results, the collaboration’s confidence in the overall profile of ’444 has increased and we are focusing our resources on this compound to move it forward as quickly as possible. This important step brings us closer to our joint goal of bringing a new treatment option to patients in this important therapeutic area.”

These studies will enrol in excess of 2,400 patients recruited globally. The ’444 LABA Phase 2b dose-optimisation study will enrol approximately 600 patients with persistent asthma who are receiving inhaled steroids. The ’698 ICS Phase 2b studies will be undertaken in three separate studies in mild, moderate and severe asthma patients with a total enrolment of 1,800 patients. All studies will be carried out using a new inhaler device. In parallel, enabling studies involving ’444 and ’698 given in combination will be undertaken prior to commencing large-scale Phase 3 combination studies.

In a recently-completed Phase 2 study, ’698 demonstrated once-a-day efficacy in patients with moderate asthma, with significant improvements in lung function in excess of 200mL seen within the first two weeks of dosing and maintained throughout the remainder of the 8 week treatment period, without any adverse effect on adrenal function (a marker of systemic steroid effect).

Darrell Baker concluded, “Our goal will be to offer patients the benefit of a once-daily medication to address a significant unmet patient need. As a leader in respiratory medicine, GSK is leveraging years of experience in the development of combination products with the goal of providing physicians and patients with an effective and innovative medicine.”

About GSK

GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit gsk.

About Theravance

Theravance is a biopharmaceutical company with a pipeline of internally discovered product candidates. Theravance is focused on the discovery, development and commercialization of small molecule medicines across a number of therapeutic areas including respiratory disease, bacterial infections and gastrointestinal motility dysfunction. Of the six programs in development, four are in late stage its telavancin program focusing on treating serious Gram-positive bacterial infections with Astellas Pharma Inc., the Gastrointestinal Motility Dysfunction program, the Horizon program (Beyond Advair collaboration) with GlaxoSmithKline plc, and TD-1792 for the treatment of serious Gram-positive bacterial infections. By leveraging its proprietary insight of multivalency toward drug discovery focused on validated targets, Theravance is pursuing a next generation strategy designed to discover superior medicines in areas of significant unmet medical need. For more information, please visit the company’s web site at theravance. THERAVANCE®, the Theravance logo, and MEDICINES THAT MAKE A DIFFERENCE® are registered trademarks of Theravance, Inc.

GlaxoSmithKline forward-looking statements

Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group’s operations are described under ‘Risk Factors’ in the Business and Prospects in the company’s Annual Report on Form 20-F for 2006.

Theravance forward-looking statements

This press release contains certain “forward-looking” statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives and future events. Theravance intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Exchange Act and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to the goals, timing and expected results of clinical and preclinical studies, statements regarding the potential benefits and mechanisms of action of drug candidates, statements concerning the goals and timing of seeking regulatory approval of our product candidates, the enabling capabilities of Theravance’s approach to drug discovery and its proprietary insights, statements concerning expectations for product candidates through development and commercialization and projections of revenue and other financial items. These statements are based on the current estimates and assumptions of the management of Theravance as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance to be materially different from those reflected in its forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, the potential that results of clinical or preclinical studies indicate product candidates are unsafe, ineffective, inferior or not superior, and delays or failure to achieve regulatory approvals and risks of collaborating with third parties to develop and commercialize products. These and other risks are described in greater detail under the heading “Risk Factors” contained in Item 1A of Theravance’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 7, 2007 and the risks discussed in our other filings with the SEC. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance assumes no obligation to update its forward-looking statements.

European Respiratory Journal Publishes Results Of Computed Tomography Analysis From Pilot Study Of Spiration’s Novel Emphysema Treatment

Spiration, Inc., a developer of novel medical devices designed to benefit patients with severe and chronic conditions of the lung, announced today that the results of a Computed Tomography (CT) study were published in the December issue of the European Respiratory Journal, a peer-reviewed scientific publication from the European Respiratory Society.

The article, titled “The computed tomography assessment of lung volume changes after bronchial valve treatment,” reported results from a pilot study of the Spiration IBV® Valve, which is intended for use as a minimally invasive treatment for severe emphysema. The valve is designed to redirect airflow from diseased portions of the lung to healthier areas to achieve improvement in disease-related health status.

High resolution computed tomography scan data from 57 patients with severe emphysema were obtained from nine North American clinical trial sites.

“The data show the association of the significant health status improvements reported by patients following bilateral bronchial valve treatment with the regional lung volume changes measured using CT,” said Harvey O. Coxson, Ph.D., of Vancouver General Hospital in Canada, lead author of the study.

The advanced CT scan analysis technology used in the study combines modern high-resolution imaging with regional volumetric analyses enabled by new software. By applying this technology to images before and after the valve procedures, researchers are able to accurately pinpoint the changes in inspired air volumes and understand the redirection of air from the diseased portions of the lung to the less-affected areas.

Steven C. Springmeyer, M.D., Spiration medical director and senior author of the study, summarized the importance of this data: “We were fortunate to merge multidetector CT and analytic software – two rapidly advancing technologies – to obtain objective data showing how the IBV Valve works in most patients. This has been of great value to us because while many patients and their doctors were seeing improvement, the classic ways to test lung function were not able to measure changes in regional lung volume.”

About the IBV Valve System

The IBV Valve System is a minimally invasive treatment that has diverse applications in both acute and chronic conditions of the lung. During the minimally invasive procedure, a catheter is passed through a bronchoscope (a flexible tube passed into the bronchial tubes through the mouth or nose) to deploy the small umbrella-shaped valves into the airways of the lungs. The valves are designed to be easily removed via a similar bronchoscopic procedure.

The IBV Valve System is currently under investigation in the U.S. as a new treatment option for the many people with severe emphysema who do not respond well to current medical therapies or are not eligible for or elect not to undergo invasive surgery such as lung volume reduction or lung transplantation. The device has received Humanitarian Device Exemption (HDE) approval from the U.S. Food and Drug Administration (FDA) to control prolonged air leaks of the lung, or significant air leaks that are likely to become prolonged, following lobectomy, segmentectomy, or lung volume reduction surgery. The IBV Valve System is marketed and distributed by Olympus in Europe, where the system has received market clearance through the CE Mark for the treatment of diseased and damaged lung, an indication that includes the treatment of emphysema and the resolution of prolonged air leaks. Olympus also has development and distribution rights for the IBV Valve System in Japan.

About Spiration, Inc.

Spiration, Inc. is committed to improving quality of life for patients with acute and chronic conditions of the lung through the development of novel therapies. Founded in 1999 in Redmond, Wash., the privately held company is backed by prominent investors including Three Arch Partners, New Enterprise Associates, Versant Ventures, New Leaf Ventures (Sprout Group), InterWest Partners, Investor Growth Capital, Saints Capital and Olympus Medical Systems Corp. For more information, visit the company’s website at spiration.

Information about the U.S. pivotal study of Spiration’s IBV Valve System may be found at emphysematrial.

Spiration, Inc.

Most U.S. States Poorly Prepared To Respond To Major Radiation Emergency Event

A survey of state health departments finds substantial gaps in preparedness for response to a major radiation emergency event, according to a report posted online today by Disaster Medicine and Public Health Preparedness, a journal published by the American Medical Association. This article as well as all of the articles in the special issue, Nuclear Preparedness, is open access and can be viewed at Disaster Medicine and Public Health Preparedness journal’s website

“Attention on public health preparedness has increased since the September 11, 2001, terrorist attacks on New York City’s World Trade Center and other sites, ” according to background information in the article. “In recent years, preparedness planning has expanded to an all-hazards approach that includes readiness to respond not only to terrorism but also to releases from unintentional technological incidents, natural disasters, and outbreaks of human diseases.” Emergency preparedness guidance related to radiation release incidents (both intentional and unintentional) has come from a collaborative group of state, county, municipal and federal organizations called the National Alliance for Radiation Readiness (NARR). As part of the NARR activities, the Council of State and Territorial Epidemiologists (CSTE) reassessed the status of radiation preparedness planning and response capabilities at the state health department level in 2010 through a survey. An original assessment was conducted in 2003.

“Thirty-eight (76 percent) state health departments responded to the survey, including 26 or the 31 states with nuclear power plants. Specific strengths noted at the state level included that the majority of states had a written radiation response plan and most plans include a detailed section for communication issues during a radiation emergency,” the authors report. Most states had completed little to no planning for public health surveillance to assess potential human health impacts of a radiation event. “Few reported having sufficient resources to do public health surveillance, radiation exposure assessment, laboratory functions and other capabilities.”

“The results of this assessment indicate that in many measures of public health capacity and capability, the nation remains poorly prepared to respond adequately to a major radiation emergency incident,” the authors write. “The most fundamental step of preparedness, development of response plans (outside of response plans for nuclear power plant emergencies), was not reported as occurring in 45 percent of states. Without a comprehensive plan, states in which a radiation emergency occurs are likely to mount inefficient, ineffective, inappropriate, or tardy responses that could result in (preventable) loss of life. With nearly half of the responding states not having a response plan, a large portion of the U.S. population is at increased risk should a radiological event occur within the country’s borders.”

In conclusion the authors suggest several steps for better preparation including additional training and resources at the state and federal levels to ensure adequate levels of preparedness for response to a possible major radiation emergency event.

Disaster Med Public Health Preparedness. 2011;5:S134-S142.

Ongoing Phase II Study Explores Potential For Detection Of Amyloid Plaque Prior To Onset Of Alzheimer’s Disease

Avid Radiopharmaceuticals presented clinical results on the development of a novel 18F-labeled PET amyloid imaging agent, 18F-AV-45, that may eventually provide a practical approach for routine brain imaging of people at risk for the development of Alzheimer’s disease. At the ICAD meeting in Chicago, Avid presented results of the exploratory IND clinical studies of three novel amyloid plaque imaging agents. The study results demonstrated that 18F-AV-45 (AV-45) was the best of the compounds studied, and allowed for rapid (?‰¤ 1 hour) imaging of amyloid plaque in Alzheimer’s Disease (AD). Brain amyloid plaques are comprised of ??-amyloid aggregates, one of the primary pathological markers of Alzheimer’s disease and a key target for new therapeutic treatments under development.

AV-45, now in Phase II clinical studies, is the first F-18 PET amyloid imaging compound to enter multi-center clinical research studies in the U.S. for the detection of amyloid plaque in patients with varying degrees of dementia. The use of the F-18 radiolabel on AV-45 allows for high quality PET imaging of amyloid plaque to be done for the first time in a community hospital or imaging clinic setting.

“The entire Alzheimer’s community dreams of a day when Alzheimer’s becomes a preventable disease. The only way to achieve this is through early detection and early treatment,” said Daniel Skovronsky, M.D., Ph.D., CEO and President of Avid. “At Avid, we are working to make this vision a reality, and believe that AV-45 PET imaging may have the potential to detect amyloid plaque pathology in the brain prior to the development of dementia. With this in mind, we have embarked on a Phase II clinical study of AV-45 in people with mild cognitive impairment, a form of memory impairment that may eventually lead to Alzheimer’s disease,” added Skovronsky.

In this study reported at the ICAD meeting, AV-45 permitted the visualization of amyloid plaque – the major pathological component of AD – within as little as 50 minutes from administration and with 10 minutes of imaging time, resulting in minimal inconvenience or delay for the patient or the imaging center. These rapid imaging characteristics of AV-45 make it very convenient for brain PET imaging at both major academic research centers as well as in the community imaging center. In addition, stable levels of AV-45 were maintained in amyloid plaque for up to 90 minutes post injection, permitting high quality PET images to be obtained over an extended period of time.

About Avid Radiopharmaceuticals Inc.

Based in Philadelphia, PA, Avid Radiopharmaceuticals Inc. is a leader in the development of products with the potential for earlier and more effective detection, diagnosis and monitoring of brain disorders. The company is a pioneer in the development of molecular imaging agents for Alzheimer’s disease that could lead to earlier diagnosis and better evaluation of drugs designed to prevent or reverse amyloid plaque build-up in the brain. Avid is currently enrolling patients in clinical studies of 18F-PET agents for imaging amyloid plaques in Alzheimer’s disease and for imaging the vesicular monoamine transporter (VMAT2) in diseases involving dopaminergic degeneration such as Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB).

Avid Radiopharmaceuticals Inc.

Anesthesia Increases Risk Of Developing Alzheimer’s Disease In Patients With Genetic Predisposition

Dr. Mar?­a Angeles Mena, Researcher at Centro de Investigaci??n Biom?©dica en Red de Enfermedades Neurodegenerativas (CIBERNED) and Director of the Neuropharmacology Laboratory at Hospital Ram??n y Cajal (Madrid, Spain), coordinated the study performed by predoctoral student Juan Perucho and others.

The study “Anesthesia with isoflurane increases long lasting behavioral changes and amyloid pathology of Alzheimer’s disease in mice” confirms that anesthesia is safe for normal mice but potentially harmful for mice with genetic risk factors for Alzheimer’s disease (AD).

Over several months, investigations have focused on analyzing the effects of the anesthesia in normal mice and in mice with mutations that produce AD.

The use of repetitive anesthesia with isoflurane (one of the most common anesthetics by inhalation) increases the risk of developing changes similar to those observed in AD brains in mice with mutations of the amyloid precursor protein (APP). This is the main conclusion of Spanish researchers coordinated by Doctors Maria Angeles Mena and Justo Garc?­a de Y?©benes, from CIBERNED (Centro de Investigaci??n Biom?©dica en Red de Enfermedades Neurodegenerativas). The work has been published in the Journal of Alzheimer’s Disease. Other participants in the study are Juan Perucho, Isabel Rubio, Mar?­a J. Casarejos, Ana G??mez, Jos?© A. Rodr?­guez-Navarro, Rosa M. Solano, from the Neurobiology and Neurology Departments at Hospital Ram??n y Cajal in Madrid.

The findings suggest a possible mechanism of developing Alzheimer. Some epidemiological studies have shown an increased prevalence of AD in patients undergoing anesthesia and surgery. Doctor Justo Garc?­a de Y?©benes states that “before surgery requiring anesthesia, it may be ideal to know the genetic background of the patients so that the drugs used and the pattern of anesthesia may be personalized accordingly.”

The linkage between the repetitive use of isoflurane anesthesia and the development of AD changes in mice with mutations indicates the advisability of testing for genetic risk factors for AD in patients prior to surgery. Until recently, the most important genetic risk factor for AD was the presence of the allele E4 of the apolipoprotein E, but recently other genetic polymorphisms of risks have been identified. Once these polymorphisms of risks are identified and their relative impact on the pathogenesis of AD are known, a simple, automatic test for risk of AD should be performed in patients, namely the elderly, undergoing surgery under general anesthesia and the anesthetic procedure should be modified accordingly. A personalized clinical model that would enable the reduction of the patient’s potential risk for AD would reduce the risk of anesthesia.

Study conclusions:

The study “Anesthesia with isoflurane increases long lasting behavioral changes and amyloid pathology of Alzheimer’s disease in mice”, confirms that anesthesia is safe for normal mice but risky for asymptomatic carriers of mutations wich produce AD.

The research has been based on the application of anesthesia twice a week during three months in normal mice and in mice with mutations (7-10 months old) that produce AD (known as APPswe ). The results show alterations produced in the brain of mice with mutations very similar to those observed in patients that have already developed Alzheimer’s disease.

Study highlights:

–Application of repetitive anesthesia in genetically altered mice increased their death rate.

– Mutant mice showed less reactivity after anesthesia was over. Their time for recovery after anesthesia was also increased.

– Repetitive anesthesia produced persistent disorders affecting behavior of mutant mice.

– Neuronal death increased in brain areas critical for cognition.

– Increased inflammatory response and deposition of beta-amyloid peptides.

– Isoflurane anesthesia of mutant mice altered the levels of chaperones (proteins which regulate the processing of abnormal proteins)

AD usually is the main cause of dementia for people over 65

Currently, over 5 million people in the first world suffer from AD, a neurodegenerative pathology that lacks a specific diagnostic test. The prevalence of this disease is also increasing in developing countries. Currently, there is no therapy that stops or reverses the progression of AD, although there are several treatments that partially improve symptoms. Researchers predict that Spain will experience a 75% increase of AD patients in 25 years.

Memory loss, language problems, incapacity for decision making and discernment are some of the main traits of this disease.

Source: IOS Press BV

New Biotechnology Discovered – Should Help Solve The Puzzles Of Cancer, Alzheimer’s, Atherosclerosis And Infectious Diseases

Researchers at UC Santa Barbara have developed a new biotechnology that enables scientists to identify and engineer protease substrates, giving them the means of crafting pharmaceuticals to outsmart disease. Their work, authored by Patrick Daugherty, an assistant professor of Chemical Engineering, and Kevin Boulware, a PhD candidate, are published online today in the Proceedings of the National Academy of Sciences.

Proteases (or peptidases) are encoded by about two percent of genes in the human genome and play key roles in nearly all diseases. They act as “molecular scissors” by attaching to specific sequences contained within other proteins, called substrates, and cutting them in specific locations. For example, proteases are responsible for digesting food, for determining the proper time for cells to die, and for removing damaged proteins from the body.

But the substrates for most proteases are unknown, and this has limited researchers’ ability to facilitate or thwart protease action. By identifying substrates, scientists gain the ability to regulate protein function, creating the capacity to speed up, slow down or eliminate particular protease actions. Daugherty’s approach also makes it easier to measure protease action and thus develop pharmaceuticals that control protease activity.

Daugherty and Boulware developed a general combinatorial approach to identify optimal substrates of proteases, using quantitative kinetic screening of cellular libraries of peptide substrates (CLiPS). The results suggest that CLiPS will be broadly useful for characterizing proteases and developing optimal substrates for therapeutic applications.

Of the roughly 1,000 proteases in the human genome, only about ten percent of the targets have been identified, but Daugherty believes that scientists will identify nearly all of them in the next five to ten years. “This technology will give us a scalable tool that will allow us to effectively tackle this challenge,” he says.

Contact: Barbara B. Gray
University of California – Santa Barbara