Menstrual Cycle Changes May Lead To New Therapies That Encourage Blood Vessel Formation For Patients With Advanced Lung Diseases

Researchers at Cleveland Clinic Lerner Research Institute have discovered that microscopic blood vessels in the lungs increase and decrease in the same rhythm as a woman’s uterine lining changes. These changes may lead to new treatments for patients with advanced lung diseases who need improved oxygen absorption.

The study, led by Serpil Erzurum, M.D., Chair, Pathobiology, Cleveland Clinic Lerner Research Institute, monitored and tested 10 healthy, non-smoking women in their early 30s during their menstrual cycles. The team found that microscopic blood vessels in the lungs increase and decrease in the same rhythm as a woman’s uterine lining changes. These blood vessels are critical to the exchange of oxygen for carbon dioxide that occurs in the lungs during breathing. The lung diffusing capacity in women increased by 10 percent when the blood vessel formation was at its peak during the menstrual cycle, demonstrating improved in gas transfer.

The results of the study, which also looked at blood vessels in mice receiving estrogen or a placebo, were published in the November issue of Journal of Applied Physiology.

The research team found that mice that received estrogen had a greater number of microvessels, and more and smaller alveoli (small air sacs in the lungs that are the work horses during gas transfer). Together the smaller alveoli and the rich networks of new micro blood vessels increase the surface area available for transferring gases.

“It’s clear that the same factors that cause blood vessel development in the uterus and ovaries during a menstrual cycle are critical factors to how well lungs transfer gases,” said Dr. Erzurum. “Our understanding of what governs gas transfer in the lung may one day lead to therapies that encourage blood vessel formation in the lungs of patients with advanced lung diseases. Improving or augmenting oxygen intake for this patient population will represent a step forward in their care.”

The research may lead to a better understanding of airflow obstruction that occurs in some asthmatic women around the time of their menstrual cycle. It may also have implications in other lung diseases that have a predilection for women such as pulmonary hypertension, or high blood pressure within the arteries in the lungs.

About Cleveland Clinic’s Lerner Research Institute

The Lerner Research Institute is home to all laboratory-based research at the Cleveland Clinic. Its mission is to understand the causes of human diseases and to develop new treatments and cures. The Lerner Research Institute is ranked among the top 10 in NIH funding among all U.S. research institutes for 2006. More than 1,100 people work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious disease. The Institute also is an integral part of the new Cleveland Clinic Lerner College of Medicine of Case Western Reserve University – training the next generation of physician-scientists.

About Cleveland Clinic

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Approximately 1,800 full-time salaried physicians and researchers at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2006, there were 3.1 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were more than 53,000 hospital admissions to Cleveland Clinic in 2006.

Cleveland Clinic

Alzheimer’s Association Statement On Florbetapir PET Amyloid Imaging

The U.S. Food and Drug Administration (FDA) Peripheral and Central Nervous System Drugs Advisory Committee did not recommend approval of florbetapir (Amyvid, Lilly/Avid) injection for imaging amyloid plaques based on the currently available data. At the same time, the committee did vote to recommend approval of florbetapir conditional on development and implementation by the company of a training program for users on how to accurately and consistently read the scans. They must train readers in a consistent technique and then re-evaluate florbetapir scans from both a recent phase III and a previous phase II clinical trial.

The committee said florbetapir appears to help detect brain plaques associated with Alzheimer’s but that more data is needed to show (1) that the scans can be properly read and interpreted, and (2) that the scans are accurate and beneficial in the population of patients who would be most likely to get the scan (and not just those specially chosen to be in a clinical trial).

Florbetapir is a radioactive dye proposed for use in Positron Emission Tomography (PET) imaging of beta-amyloid plaque deposits to help rule out Alzheimer’s disease.

The Alzheimer’s Association supports an FDA advisory committee recommendation of approval of florbetapir, once its current questions are thoroughly answered, but we acknowledge that it is a double-edged sword.

On one hand, FDA approval of this product will expand the clinical and research opportunities for amyloid imaging by making this brain imaging tool more widely available to the field. On the other hand, the fact that all of the potential uses of this product are not crystal clear tempers our enthusiasm. Further research is needed to understand the appropriate use of florbetapir-PET imaging – or any other imaging technology – in Alzheimer diagnosis.

In the doctor’s office, having a negative scan using this tool (meaning no detectable amyloid buildup in the brain) may be helpful to clinicians in ruling out Alzheimer’s disease as the cause of the memory and thinking changes that the person being tested is experiencing. However, a positive scan (showing that there is amyloid buildup in the brain) has limited utility at this point. Having amyloid buildup in your brain does not mean for certain that you have Alzheimer’s disease.

Important note of clarification: While a negative scan with this brain imaging tool may be able to help rule out Alzheimer’s as a cause of the memory and behavior changes the person is experiencing, it should not be interpreted to mean that the person is well. It most likely means that another cause, other than Alzheimer’s disease – such as vascular dementia caused by small strokes, or the interaction of multiple drugs the person is taking, or complications of alcoholism, or any one of a number of possible causes for dementia – still has to be found for the problems
he or she is experiencing. Nonetheless, Alzheimer’s disease is the most common cause of dementia in older adults.

Despite the concerns and complications, we believe it is valuable to the Alzheimer field – to the pursuit of better Alzheimer diagnostics, treatments and preventions – to have this product more widely available.

Because so many unanswered questions remain about Alzheimer diagnosis and treatment, next steps for Alzheimer research are very important. Most importantly, we need to correct the chronic underfunding of Alzheimer’s disease research by the U.S. federal government. As the leading care, research and advocacy organization for Alzheimer’s disease, the Alzheimer’s Association plans to work closely with the Administration, the Secretary of Health and Human Services and members of Congress to ensure swift, aggressive implementation of the recently-passed National Alzheimer’s Project Act.

In the biomarkers area, the Alzheimer’s Association is proud to be a sponsor of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and a major sponsor of World Wide ADNI (WW-ADNI) as part of our global research strategy to defeat Alzheimer’s. ADNI’s mission is to develop biomarkers of Alzheimer’s in elderly subjects. A major goal of the study has been to establish and validate MRI and PET images, cerebral spinal fluid, and blood biomarkers as predictors of the disease. WW-ADNI unites leading international investigators in a common effort to:

– Help predict and monitor the onset and progression of Alzheimer’s disease.

– Establish globally recognized standards to identify and diagnose Alzheimer’s disease.

– Document cognitive changes linked to physical changes.

– Share data across the international research community.

Alzheimer’s is the sixth-leading cause of death in U.S. adults. Distressingly, of the 10 leading causes of death, Alzheimer’s is by far the fastest growing – increasing more than 50 percent from 2000 to 2007. Alzheimer’s disease kills more Americans than breast cancer and prostate cancer combined. And, Alzheimer’s is the only one of the top 10 causes of death where we have no method to prevent it, cure it, or slow its progression.

Source:

Alzheimer’s Association

Innovative Respiratory Stress Test Can Quickly Detect Significant Coronary Artery Disease In A Noninvasive Setting

Newly published data shows using a Respiratory Modulation Response (RMR) is a novel, non-invasive measure to quickly and accurately detect the presence of significant coronary artery disease (sCAD). Patients in the study with sCAD had a lower RMR compared to patients without, regardless of their risk factors or clinical history of angina, previous myocardial infarction (MI), or angioplasty. These data, published in the current issue of Euro Intervention Journal, demonstrate that RMR was lower in patients with significant CAD compared to those with non-significant CAD (P

Novel Gene Therapy Shows That Clearing Toxic Proteins Inside Brain Cells Prevents Plaque Formation Outside Neurons

Gene therapy that boosts the ability of brain cells to gobble up toxic proteins prevents development of Alzheimer’s disease in mice that are predestined to develop it, report researchers at Georgetown University Medical Center. They say the treatment – which is given just once – could potentially do the same in people at the beginning stages of the disease.

The study, published online in Human Molecular Genetics, demonstrates that giving brain cells extra parkin genes promotes efficient and effective removal of amyloid particles believed to be destroying the neurons from the inside. This revved up protein disposal process prevents the cells from dying and spewing amyloid proteins into the brain, where they stick together and clump into plaque, they say.

“At its core, this is a simple garbage in-garbage out therapy, and we are the first to show that this gene attacks amyloid beta inside brain cells for degradation,” says the study’s lead investigator, neuroscientist Charbel E-H Moussa, M.B., Ph.D.

He adds that the strategy may work for other brain disorders. “Many neurodegenerative diseases are characterized by a toxic build-up of one protein or another, and this approach is designed to prevent that process early-on,” he says.

The novelty of Moussa’s work is that he believes diseases like Alzheimer’s starts when neurons are unable to get rid of toxic amyloid beta that begins to build up inside neurons – an idea that he says remains controversial, but is rapidly gaining acceptance among neuroscientists.

Moussa has documented a connection between Alzheimer’s, Parkinsonism (such as Dementia with Lewy Bodies, or DLB), and Down’s syndrome, finding that what these disorders have in common is a build-up of amyloid beta. In Parkinsonism, or secondary Parkinson’s disease, the toxic protein may be found in Lewy bodies, which are clumps of protein that clogs the brain of people with DLB, and in some people with Parkinson’s disease. People with Down’s syndrome produce too much amyloid protein because they have three copies of the chromosome (21) that generates amyloid. “They have dementia because they have too much amyloid in their brains,” Moussa says.

He and his colleagues developed a unique model system that mimics the early stages of these diseases. They used a lentivirus, a modified, inert form of HIV, to deliver amyloid beta into the motor cortex of rats, and showed that this produced a buildup of amyloid beta inside neurons, but not an accumulation outside of the cells. They hypothesize that once the stockpile of amyloid beta inside the cell reaches a critical level, neurons burst, and the amyloid beta proteins begin to stick together in the space between brain cells, forming plaque.

Additionally, tau pathology is triggered by amyloid beta inside neurons, causing tau malfunctions, and the whole process results in increased brain inflammation.

So what Moussa and his team tested was removal of the amyloid beta buildup inside neurons. In earlier studies, they used the same model gene delivery system to express extra parkin in the brain of rats at the same time they received amyloid beta. Parkin is part of the ubiquitin ligase complex of proteins that helps target other proteins for degradation inside of the cell, and mutations in parkin are known to cause an early onset familial form of Parkinson’s disease. In the earlier studies, the researchers found that in rats that had received amyloid beta, parkin effectively cleared the protein away.

In this study, they used triple transgenic mice that are often used as a model of human Alzheimer’s disease. They develop intracellular amyloid beta at six months of age and extracellular amyloid beta plaque about 3-6 months later.

The researchers injected parkin in one side of the brain of young mice, and left the other side untouched, as a control to compare effects of the treatment.

They found that providing brain cells with about 50 percent more parkin protein activates two parallel garbage-removal processes within the brain. One is ubiquitination, in which errant proteins are targeted for destruction and recycling within the cell. The other process is autophagy, in which membranes form around damaged mitochondria (the cell’s power plants) and these membranes fuse with lysosomes that destroys the contents. This is particularly important, Moussa says, because damaged mitochondria have been found to clog the insides of neurons affected by Alzheimer’s disease, and the extra parkin seems to help clear them. That allows the cells to produce new and healthy mitochondria.

“With a normal amount of parkin, the cells are overwhelmed and cannot remove molecular debris. Extra parkin cleans everything,” Moussa says.

In a second experiment, the research team found that mice given parkin genes through the lentiviral vector had 75 percent less amyloid beta plaque in their brains, compared to mice that were not treated, and that neuronal cell death was also reduced by that amount. They also showed that parkin cleared away so much amyloid beta inside cells that the function of normal glutamate neurotransmission in the hippocampus was restored. This is especially important, the authors say, because glutamate is key to memory formation, retention and retrieval. “Hypothetically, these damaged cells could restart memory formation,” Moussa says.

Moussa says the research team has done all the animal work necessary for an application to begin studying the treatment in humans, starting with an analysis of safety.

He adds that if these experiments are successful, the goal will be to use the treatment as early as possible in the course of a neurodegenerative disease. “Our hope is to stop the whole process early on, but if it is later, perhaps we can halt progression,” he says.

Notes:

Co-authors of the study include Preeti Khandelwa, PhD, Alexander Herman, MS, William Rebeck, PhD, Hyang-Sook Hoe, PhD.

The study was supported by the National Institutes of Health. The authors report having no personal financial interests related to the study.

Source:
Karen Mallet
Georgetown University Medical Center

UK top of asthma league in Europe

Asthma in the EU (% of population)
UK: 13.8
Finland: 11.0
Ireland: 10.5
Netherlands: 8.7
AVERAGE: 7.2
France: 6.9
Germany: 4.7
The UK has by far the highest rates of asthma in Europe, according to a survey carried out by the European Commission.

Rates of asthma in the UK are currently almost double the EU average, 13.8% of the population compared with 7.2%.

In Germany, only 4.7% of the population has been diagnosed with the disease, which can prove fatal in the most severe cases.

Here, asthma kills 1,500 people a year and costs the NHS an estimated ?850 million to treat.

No-one is sure why the UK has such high rates of reported asthma.

Possible causes

Some scientists believe that diet, exposure to pollution and perhaps even far cleaner living conditions may be somehow to blame.

Even double glazing (windows with double layer of glass) and central heating have been suggested as a contributory factor, with some claiming that ‘sealed’ living conditions create a perfect environment for the development of allergic illnesses.

The rate among young people is six times higher than it was 25 years ago, and is accompanied by soaring rates of other allergic conditions such as eczema and hayfever.

A survey carried out in the UK revealed that almost a quarter of those diagnosed with asthma had ‘significant restrictions’ on their daily lives.

Treatment

Despite the high rate of diagnosed asthma, only 9% of UK people are receiving active long-term treatment for the condition.

And the overall rate of allergies is not the highest in Europe, at 19.1%, with rates into to mid-20s reported in Sweden, Finland and Denmark.

A spokesman for the National Asthma Campaign said that the causes of the illness were hard to pin down.

She said: ‘It’s true that we have some of the highest rates of asthma – the rates of wheeze among 13 to 14-year-olds may be the highest in the world.’

The EU report also showed the UK’s rates of other chronic illnesses compared with our European neighbours.

Levels of diabetes and high blood pressure in the UK are fairly low compared with most other EU states, although the UK is close to the top of the EU league table for rheumatism and arthritis.

Overall, though, the Portuguese, Finns and Danes ahve the highest incidence of chronic disease in Europe.

New York State Approves Quest Diagnostics’ Fragile X Syndrome Test

An accurate, faster testing option to identify female carriers and other patients with genetic abnormalities that cause Fragile X Syndrome is now available to physicians in all fifty states with the recent approval in New York. Fragile X is the leading cause of inherited mental retardation and the most common known single gene cause of autism.

XSense®, Fragile X with Reflex, from Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading diagnostic company, has been approved by New York State’s Department of Health. XSense is the first test for Fragile X Syndrome to be approved by New York to employ a new laboratory analysis technique that bypasses the need to perform the Southern Blot DNA analysis method in 99 percent of cases. The use of Southern Blot, which can take several days to weeks to perform, has hampered the lab industry’s ability to widely provide Fragile X testing. XSense results are reported in about a week for the vast majority of patients.

With the approval, Quest Diagnostics can offer the test to physicians in New York as well as in all other U.S. states. New York is the only U.S. state with an independent regulatory review process for laboratory developed tests, which are also regulated at the federal level.

“New York’s approval is significant because it means a new, highly innovative genetic analysis technique for Fragile X has fulfilled state-required quality standards that are widely regarded in the lab industry as highly rigorous,” said Charles Strom, M.D., Ph.D., medical director, Genetic Testing Center, Quest Diagnostics Nichols Institute. “Fragile X can be a devastating diagnosis, given the severe disability it causes many patients. While it is highly prevalent, Fragile X is not widely tested for, due in part to technical limitations with conventional tests that our XSense technique largely surmounts.”

Physicians can use XSense to aid their identification of women who, as carriers, may be unaffected or slightly affected by Fragile X syndrome, but are at risk of passing it to offspring, regardless of the father’s genetics. It may also aid in the diagnosis of male and female patients using blood and other specimen types. An estimated one in 260 women are genetic carriers of Fragile X Syndrome, according to the National Fragile X Foundation, although recent research by scientists at Quest Diagnostics and other organizations suggest carrier prevalence may be even higher.

“XSense is a step forward to the day when the medical community can seriously consider the option to provide population-wide quality testing for Fragile X in much the same way we now offer population screening for other hereditary disorders,” said Dr. Strom.

A couple is statistically more likely to pass Fragile X to their offspring than two common hereditary disorders, cystic fibrosis or Tay-Sachs Disease, which guidelines support for wide population screening. In most states, newborns are routinely tested for cystic fibrosis. While medical guidelines recommend Fragile X testing for some patients, such as women seeking reproductive counseling with a personal or family history of mental retardation, they do not support population-based carrier or newborn testing, in part due to technical lab-testing hurdles.

A study performed and funded by Quest Diagnostics and published in the March 2010 issue of Genetics in Medicine, the official publication of the American College of Medical Genetics (ACMG), found that the XSense technique showed 100% agreement with the standard widely used lab-testing method, which requires a DNA analysis technique called Southern Blot in about 20 percent of cases. Southern Blot can take several days to weeks to perform, making it generally unsuitable for high-volume testing applications. In the study, the XSense technique bypassed the need for Southern Blot in more than 99 percent of cases.

The investigators concluded that the XSense test is highly accurate, and may be suitable for high-volume population screening and diagnostic testing on a range of patients, including women and newborns.

Earlier this month, Genetics in Medicine published a report that found there is adequate research data to support population screening of women of childbearing age for Fragile X syndrome. The report was based on a review and analysis of eleven prior studies of Fragile X screening in women of reproductive age.

About XSense®, Fragile X with Reflex

XSense, Fragile X with Reflex, test identifies abnormalities of the fragile X mental retardation 1 (FMR1) gene residing on the X chromosome. The number of times a certain pattern of DNA, called CGG, occurs determines whether a person has a premutation and is a carrier or has a full mutation and has the disorder. XSense employs a technique called triplet-primed polymerase chain reaction by capillary electrolysis (triplet-primed PCR-CE) to assess the number of CGG repeats without Southern Blot in about 99 percent of cases. Quest Diagnostics is the first U.S. company to publish peer reviewed data on this new Fragile X syndrome test technique and bring it to market. Quest Diagnostics offers XSense in alignment with current guidelines for Fragile X Syndrome testing.

About the New York State Department of Health Clinical Laboratory Evaluation Program

New York approves laboratory-developed tests that are not FDA cleared before allowing them to be performed on patients in the state. In order to gain approval, labs must validate that a test performs as it is intended, based on validation data collected according to the U.S. Center for Disease Control and Prevention’s Clinical Laboratory Improvement Amendments and New York State requirements. New York is the only state that independently approves laboratory-developed tests.

Source: Quest Diagnostics

Alzheimer’s, Parkinson’s Diseases Could Be Halted By Protecting Neurons

Researchers at Southern Methodist University (SMU) and The University of Texas at Dallas (UTD) have identified a group of chemical compounds that slow the degeneration of neurons, a condition behind old-age diseases like Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS).

Their findings are featured in the November 2008 edition of Experimental Biology and Medicine. SMU Chemistry Professor Edward R. Biehl and UTD Biology Professor Santosh D’Mello teamed to test 45 chemical compounds. Four were found to be the most potent protectors of neurons, the cells that are core components of the human brain, spinal cord and peripheral nerves.

The most common cause of neurodegenerative disease is aging. Current medications only alleviate the symptoms but do not affect the underlying cause – degeneration of neurons. The identification of compounds that inhibit neuronal death is of urgent and critical importance.

The synthesized chemicals identified by Biehl and D’Mello, called “3-substituted indolin-2-one compounds” are derivatives of another compound called GW5074 which was shown to prevent neurodegeneration in a past report published by the D’Mello lab. While effective at protecting neurons from decay or death, GW5074 is toxic to cells at slightly elevated doses, which makes it unsuitable for clinical testing in patients.

The newly identified, second generation compounds maintain the protective feature of GW5074 but are not toxic – even at very high doses – and hold promise in halting the steady march of neurodegenerative diseases like Alzheimer’s and Parkinson’s.

“Sadly, neurodegenerative diseases are a challenge for our elderly population,” D’Mello said. “People are living longer and are more impacted by diseases like Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis (ALS) than ever before – which means we need to aggressively look for drugs that treat diseases. But most exciting now are our efforts to stop the effects of brain disease right in its tracks. Although the newly discovered compounds have only been tested in cultured neurons and mice, they do offer hope.”

Source: Kim Cobb

Southern Methodist University

CIGNA Offers Free Nine-Month Autism Education Series Starting In September

Starting in September, CIGNA will offer a series of free monthly telephone seminars to help people better understand the physical, mental, and emotional challenges in children who may display the symptoms of developmental disorders like autism and Asperger syndrome. These one-hour seminars are open to any parent or caregiver who is interested in learning more about autism and autism spectrum disorders.

Registration isn’t required and people can choose to listen to the entire series or any individual session that interests them. Each session will feature an expert guest presenter who will speak for about 40 to 45 minutes, followed by a question and answer session. Playback of each session will be available for people who are unable to listen to the live sessions.

Each program in the series will begin at 1 p.m. Eastern time so that it’s convenient for people in all time zones to listen and participate. To listen to a seminar, call toll-free 1-800-214-0745 and enter passcode 121391 when prompted.

Information about the first three programs in the series is listed below. Click here for a schedule of the entire series.

– September 9: “Educating First Responders About Autism and What Families Can Do to Prepare for Emergency Situations.” Guest presenter: Marianne Toedtman, R.N. M.N., Assistant National Director of Outreach and Resources, Autism Speaks.

– October 14: “Tips for School Success.” Guest presenter: Cathy Pratt, Ph.D., Director of the Indiana Resource Center for Autism, Indiana Institute.

– November 11: “The Role of Adaptive Behavior in Autism Spectrum Disorders: Implications for Functional Outcome.” Guest presenter: Celine Saulnier, Ph.D., Training Director, Autism Program, Yale Child Study Center.

“Sometimes it can be challenging for families to access helpful, reliable and practical information about autism spectrum disorders,” said Neal Cohen, LMHC, LPC, vice president of behavioral operations at CIGNA. “We’re pleased to offer this informative educational series, which is a collaboration between CIGNA and the many organizations that provide support, advocacy, and education for families in the autism community.”

CIGNA’s autism education series is intended to provide general information to the public. People who have specific questions and have CIGNA behavioral health care benefits should contact their health advocate.

Source:

CIGNA

Experts At Anavex Offer A Primer On Promising ‘Oxidative Stress’ Theory

As trials on anti-amyloid vaccines continue to fail in the search for a viable Alzheimer’s drug, a new approach – oxidative stress – is starting to emerge as a contender.

Anavex Life Sciences (AVXL.OB) is leading this promising avenue of research. It has developed an Alzheimer’s drug candidate based on the theory that oxidative stress, not amyloid-beta plaques, is the cause of the disease. Oxidative stress is a type of damage to the body’s tissues caused by the destructive action of certain forms of oxygen.

To help people better understand the science behind oxidative stress, Anavex offers this helpful primer:

What is Oxidative stress?

We are all familiar with processes like the rusting of iron, oil and butter turning rancid and fruits turning brown after prolonged exposure to air. All these phenomena are caused by exposure to oxygen in a process known as oxidation. Similar effects are known to happen inside our bodies in the molecular and cellular level, all because of the destructive action of a form of oxygen known as Reactive Oxygen Species (ROS). This destructive nature of oxygen comes in contrast to its unconditional necessity for the survival of all living aerobic organisms.

The term oxidative stress is used to describe a state in which the equilibrium between the production of ROS and the body’s protective mechanisms (antioxidants and repair mechanisms) has been compromised, resulting in the oxidative damage of cells, tissues and organs. Moreover, ROS in the state of oxidative stress can impair several cellular signaling pathways that may result in the onset of age related diseases.

The Oxidative Stress And Alzheimer’s Disease

A growing number of publications have supported the idea that oxidative stress may be the real cause of Alzheimer’s. For example, in “Involvement of Oxidative Stress in Alzheimer’s Disease,” published in the Journal of Neuropathology and Experimental Neurology in 2006, study leader Dr. Akihiko Nunomura pointed to extensive evidence of mechanistic and chronological links between oxidative stress and a number of key characteristics of the disease.

Interestingly, this research also suggests that amyloid beta, which can act as an anti-oxidant, could in fact be initially produced by the body as it tries to combat the disease, only later turning toxic as the substance accumulates in large amounts. In other words, amyloid-beta could be the body’s early protective reaction to the disease – suggesting that its removal from the brain during the early stages of Alzheimer’s could in fact do more harm than good.

This theory is consistent with a number of factors for which the amyloid-beta hypothesis has been unable to account. There are reports, for instance, of individuals with amyloid-beta loads equivalent to Alzheimer’s patients who do not suffer from the disease, as noted by R. J. Castellani et al in a 2006 article in the American Journal of Alzheimer’s Disease and Other Dementias.

In addition, scientists have found a weak correlation between the amount of amyloid beta present in the brains of Alzheimer’s sufferers and the severity of the illness. Furthermore, even though some test drugs reduce the amount of amyloid-beta in the brain, this is not correlated with substantial improvements in cognitive functioning.

Promising Pre-clinical Studies

Meanwhile, Anavex’s alternative approach is showing great promise in early-stage testing. Anavex’s drug candidate, known as ANAVEX 1-41, uses sigma receptors, a unique class of receptor molecules, to guard against oxidative stress and repair cells compromised by its effects. In advanced pre-clinical studies, ANAVEX 1-41 appeared to provide neurons with potent protection from oxidative stress. It also prevented amyloid beta from becoming toxic and causing any follow-on damage. Moreover, ANAVEX 1-41 reduced memory deficits in animal test subjects – a particularly notable finding, given the quest for a drug that can actively reverse the effects of the disease.

A program of further work is currently underway to further assess the compound, including ongoing pre-clinical studies being carried out in collaboration with the Universit?© Montpellier in France. The company is moving forward aggressively with this work, which is designed to pave the way for a rapid move towards human testing, expected to commence in late 2008 or early 2009.

While much still needs to be done, Anavex is enormously pleased with its progress to date on this promising new approach to combating one of the world’s most complex and devastating diseases.

About Anavex Life Sciences Corp.

Anavex Life Sciences Corp. is an emerging biopharmaceutical company engaged in the discovery and development of novel drug targets for the treatment of cancer and neurological diseases such as Alzheimer’s and depression. The company’s proprietary SIGMACEPTOR™ Discovery Platform involves the rational design of drug compounds that fulfill specific criteria based on unmet market needs and new scientific advances. Selected drug candidates demonstrate high, non-exclusive affinity for sigma receptors, which are involved in the modulation of multiple cellular biochemical signaling pathways. anavex

ANAVEX’s SIGMACEPTOR™-N program involves the development of novel and original drug candidates that target neurological and neurodegenerative diseases (Alzheimer’s disease, epilepsy, depression, etc.) The company’s lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for anti-amnesic, neuroprotective, anti-apoptotic, anti-oxidative, anti-inflammatory, anti-convulsive, anti-depressant and anxiolytic properties. The company believes that oxidative stress, not amyloid-beta, is the cause of Alzheimer’s. ANAVEX 1-41, uses sigma receptors, a unique class of receptor molecules, to guard against oxidative stress and repair cells compromised by its effects. So far, through the advanced pre-clinical phase of development, the compound has performed extremely well in well-recognized animal models of Alzheimer’s disease, underscoring the promise of this alternative approach to the disease.

ANAVEX SIGMACEPTOR™-C program involves the development of novel and original drug candidates targeting cancer. The company’s lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for selective pro-apoptotic, anti-metastatic and low toxicity properties in various types of solid cancers such as colon, prostate, breast and lung. ANAVEX 7-1037 has already demonstrated its ability to significantly delay the growth of cancerous tumors in patient-derived xenografts during advanced pre-clinical studies.

Theravance Announces FDA Acceptance Of Telavancin NDA For The Treatment Of Hospital-Acquired Pneumonia

Theravance, Inc. (NASDAQ: THRX) announced that the U.S. Food & Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for telavancin, a novel, bactericidal, once-daily injectable investigational antibiotic, for the treatment of nosocomial pneumonia (also known as hospital-acquired pneumonia, or HAP) caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). The FDA has established a goal of a standard 10-month review of the telavancin NDA, resulting in a Prescription Drug User Fee Act (PDUFA) date of November 26, 2009. The NDA filing triggers a milestone payment of $10 million from Theravance’s partner, Astellas Pharma Inc. This is the second telavancin NDA filed with the FDA, which is currently reviewing telavancin for the treatment of complicated skin and skin structure infections (cSSSI).

“We are very pleased with the FDA’s acceptance of our NDA submission,” said Rick E Winningham, Theravance’s Chief Executive Officer. “This is an important potential additional indication for telavancin due to the significant unmet medical need in HAP. Today, there are limited options for physicians treating patients with these serious infections. We look forward to collaborating with the FDA on its review of our NDA.”

About Telavancin

Telavancin is a bactericidal, once-daily injectable investigational antibiotic with a multifunctional mechanism of action. Telavancin was discovered by Theravance in a research program dedicated to finding new antibiotics for serious infections due to Staphylococcus aureus, including MRSA, and other Gram-positive bacteria. Telavancin inhibits the formation of the bacterial cell wall and disrupts bacterial cell membrane function. Theravance believes the additive mechanisms of action seen with telavancin speed bacterial killing while also reducing the risks of inducing resistance to telavancin or cross-resistance with other antibiotics. Telavancin has been studied in two Phase 3 programs, one in cSSSI and one in HAP, both of which demonstrated non-inferiority in the all-treated (AT) and clinically evaluable (CE) patient populations versus vancomycin. Theravance believes these clinical programs comprise the largest global studies ever conducted in patients with confirmed MRSA infections. In addition to the HAP NDA, the FDA is currently reviewing Theravance’s telavancin NDA for the treatment of cSSSI.

About ATTAIN 1 and ATTAIN 2 Clinical Studies

The telavancin NDA is based on data from two large, multi-center, multinational, double-blind, randomized Phase 3 clinical studies, ATTAIN 1 and ATTAIN 2, in which 1,503 patients were enrolled and treated, 464 of whom were infected with MRSA. Patients with HAP suspected or proven to be caused by Gram-positive bacteria were randomized (1:1) to receive either telavancin 10 mg/kg IV once daily or vancomycin 1 g IV every 12hr (the protocols allowed vancomycin dosage to be modified per site-specific guidelines). For patients with suspected or proven polymicrobial infections involving Gram-negative and/or anaerobic bacteria in addition to the Gram-positive organisms for which study medication therapy was used, aztreonam, piperacillin-tazobactam, and/or metronidazole was allowed. The objective of each study was non-inferiority of telavancin versus vancomycin in clinical cure rate at the test-of-cure visit. Determination of clinical cure was based upon physician-judged resolution of clinical signs and symptoms of HAP.

In both studies, telavancin achieved the objective of non-inferiority in the all-treated (AT) and clinically evaluable (CE) patient populations. In the ATTAIN studies, 82% of telavancin-treated patients and 81% of those who received vancomycin experienced one or more treatment-emergent adverse events. The most common adverse events were diarrhea, constipation, anemia and renal adverse events. With regard to changes in the QTc interval, there were similar proportions of patients in each group who experienced a post-baseline maximum value of greater than 500 milliseconds or a maximum change from baseline of greater than 60 milliseconds.

About the Telavancin Collaboration

In November 2005, Theravance entered into a collaboration arrangement with Astellas Pharma Inc. for the development and commercialization of telavancin worldwide except Japan. In July 2006, Theravance and Astellas expanded the collaboration to include Japan. Under the terms of the collaboration, Theravance will lead the development of and U.S. regulatory activities for telavancin for the treatment of cSSSI and HAP, and will collaborate substantially with Astellas in marketing in the United States for the first three years. Astellas will lead all other development, regulatory, manufacturing, sales and marketing activities.

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. The company’s key programs include: telavancin for the treatment of serious Gram-positive bacterial infections with Astellas Pharma Inc. and the Horizon program and Bifunctional Muscarinic Antagonist-Beta2 Agonist (MABA) program with GlaxoSmithKline plc. By leveraging its proprietary insight of multivalency toward drug discovery focused primarily 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.

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 regarding the potential benefits and mechanisms of action of drug candidates, statements concerning the timing of seeking regulatory approval of our product candidates (including with respect to telavancin statements regarding any expectation that regulatory authorities will approve telavancin on the basis of existing preclinical and clinical data or at all) and the enabling capabilities of Theravance’s approach to drug discovery and its proprietary insights. 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, risks related to the potential that results of clinical or preclinical studies indicate product candidates are unsafe or ineffective, delays or failure to achieve regulatory approvals for, or to successfully launch, product candidates, risks of relying on third-party manufacturers for the supply of our product candidates 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 Theravance’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 26, 2009 and the risks discussed in our other periodic 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.

Source
Theravance