The U.S. Food and Drug Administration approved Actemra (tocilizumab) on Friday to treat adults with moderate to severe rheumatoid arthritis who have not adequately responded to or cannot tolerate other approved drug classes for rheumatoid arthritis.
Actemra recommended use is limited to patients who have failed other approved therapies because of serious safety concerns that were noted in clinical studies. These safety concerns include elevated liver enzymes, elevated Low-density lipoprotein (LDL) or bad cholesterol, hypertension, and gastrointestinal perforations.
"Physicians and patients need to be aware of the risk of serious adverse effects of Actemra and make informed decisions regarding its benefits and risks in the treatment of individual patients," said Bob Rappaport, M.D., director of the Division of Analgesics, Anesthetics and Rheumatology Products in the FDA's Center for Drug Evaluation and Research.
The FDA is requiring the sponsor to conduct a post-marketing clinical trial to further evaluate the long-term safety of Actemra. Specifically, the FDA wants to evaluate the impact of elevated LDL cholesterol and blood pressure seen in some patients in shorter-term trials on the cardiovascular health of patients treated with Actemra.
In addition, a Risk Evaluation and Mitigation Strategy (REMS) will require the drug sponsor to implement a Communication Plan for physicians informing them how to appropriately monitor their patients for liver and/or gastrointestinal side effects. The REMS will include a Medication Guide to ensure that patients are informed of the benefits and risks of Actemra.
Actemra works by blocking the action of interleukin-6, an immune system protein that is overabundant in people with rheumatoid arthritis.
The effectiveness and safety of Actemra was determined in five clinical trials in adult patients with active rheumatoid arthritis. In all of the trials, patients treated with Actemra experienced greater improvement in their tender or swollen joints than patients treated with a placebo.
The most common adverse reactions in clinical trials were upper respiratory tract infections, headache, inflammation of the nose or nasal passage, high blood pressure and increased liver enzymes. Elevations in the LDL or bad cholesterol were also seen in some patients, some of whom required the addition of lipid lowering agents.
Patients treated with Actemra are at increased risk for developing serious infections. Most patients who developed these infections in clinical trials were also taking other drugs that suppress the immune system such as methotrexate or corticosteroids.
Actemra is marketed by San Francisco-based Genentech Inc., a subsidiary of the Roche Group.
Source
U.S. Food and Drug Administration
View drug information on Actemra.
понедельник, 30 мая 2011 г.
Rheumatology Specialist Nurses: ??100 Million "added Value" To NHS Per Year, Wales
Every rheumatology specialist nurse increases efficiency in the NHS by a quarter of a million pounds each year according to new research published by the Royal College of Nursing at its annual Congress in Bournemouth.
By managing the bulk of the outpatient workload, rheumatology specialist nurses free up hundreds of appointments for new patients to be seen by a consultant - this represents a saving of ??175,168 per nurse each year through increased efficiency. Additionally, as a result of the telephone support specialist nurses provide, many GP appointments can be freed up for other patients, equating to a further ??73,588 saving per nurse.
The UK-wide study - Clinical nurse specialists: adding value to care - monitored the working pattern of rheumatology specialist nurses over a year using a software based modelling tool to determine how their time is spent.
The research published today also found that providing administrative support for rheumatology specialist nurses would free up more than six hours of their working week, meaning they could devote even more time to patient care, resulting in further savings to the NHS.
This latest study adds further weight to the College's recent warning that cutting specialist nurse services for people with long term conditions would be a false economy. The RCN is now calling for the methodology to be rolled out to cover all specialist nurses to identify the true extent of savings that could be made.
Specialist nurse posts save millions of pounds from health budgets through reduced complications, fewer hospital re-admissions and the expert long term management of conditions. They also provide many patients and families with a lifeline which no other service can offer.
In spite of this, a recent RCN survey of 60 leading health organisations representing thousands of people with a long-term condition found that only a third (36%) of respondents felt that everyone who needed specialist nursing currently received it. The survey also found:
- More than a third (37%) of respondents had seen cuts in services over the last 12 months
- More than half (57%) were concerned that posts will be threatened in the near future
- Almost all (95%) of the respondents who had seen cuts in services say it is the NHS, rather than other joint-funders, who have cut or reduced funding for specialist nurses
Tina Donnelly, Director of the Royal College of Nursing in Wales, said: "Specialist Nurses work in a defined area of practice - they may work at advanced levels in a specialist role or simply focus their practice in one particular area. The role is often about patient communication, teaching and support of self management of disease and illness, reviewing medication, and organising the patient pathway and access to other services. Patients with long term conditions frequently identify the specialist nurse as one of the most important healthcare professionals."
"This study looks at the value of specialist nursing in rheumatology; however, we know that similar findings could be found in other areas. Advanced and Specialist Nurses make a difference to patients lives and have a beneficial impact on the health service they work in. The roles bring many benefits to patients including continuity of care, access to expertise, improved clinical outcomes, and an excellent relationship between patient and healthcare professional. Another area of benefit is the accessibility and completeness of the services provided."
In its election manifesto, the RCN is calling for every patient with a long-term condition to have guaranteed access to specialist nursing care.
Notes
The study findings will be presented at the RCN Annual Congress 2010 fringe event "Capturing the essence and demonstrating the value of clinical nurse specialists" at 5:45pm on Monday 26th April 2010.
The study used Pandora, a software-based modelling tool, to record the complex activity of clinical specialist nurses working in the field of rheumatology between March 2009 and March 2010. It recorded the work of 99 rheumatology specialist nurses spread across the four countries of the UK.
Specialist nurses are dedicated clinical experts who are able to spend time with patients with a particular condition, and help them with everything from drug treatments to exercise plans, and help to ensure that patients have the highest possible quality of life.
Source
Royal College of Nursing (RCN)
By managing the bulk of the outpatient workload, rheumatology specialist nurses free up hundreds of appointments for new patients to be seen by a consultant - this represents a saving of ??175,168 per nurse each year through increased efficiency. Additionally, as a result of the telephone support specialist nurses provide, many GP appointments can be freed up for other patients, equating to a further ??73,588 saving per nurse.
The UK-wide study - Clinical nurse specialists: adding value to care - monitored the working pattern of rheumatology specialist nurses over a year using a software based modelling tool to determine how their time is spent.
The research published today also found that providing administrative support for rheumatology specialist nurses would free up more than six hours of their working week, meaning they could devote even more time to patient care, resulting in further savings to the NHS.
This latest study adds further weight to the College's recent warning that cutting specialist nurse services for people with long term conditions would be a false economy. The RCN is now calling for the methodology to be rolled out to cover all specialist nurses to identify the true extent of savings that could be made.
Specialist nurse posts save millions of pounds from health budgets through reduced complications, fewer hospital re-admissions and the expert long term management of conditions. They also provide many patients and families with a lifeline which no other service can offer.
In spite of this, a recent RCN survey of 60 leading health organisations representing thousands of people with a long-term condition found that only a third (36%) of respondents felt that everyone who needed specialist nursing currently received it. The survey also found:
- More than a third (37%) of respondents had seen cuts in services over the last 12 months
- More than half (57%) were concerned that posts will be threatened in the near future
- Almost all (95%) of the respondents who had seen cuts in services say it is the NHS, rather than other joint-funders, who have cut or reduced funding for specialist nurses
Tina Donnelly, Director of the Royal College of Nursing in Wales, said: "Specialist Nurses work in a defined area of practice - they may work at advanced levels in a specialist role or simply focus their practice in one particular area. The role is often about patient communication, teaching and support of self management of disease and illness, reviewing medication, and organising the patient pathway and access to other services. Patients with long term conditions frequently identify the specialist nurse as one of the most important healthcare professionals."
"This study looks at the value of specialist nursing in rheumatology; however, we know that similar findings could be found in other areas. Advanced and Specialist Nurses make a difference to patients lives and have a beneficial impact on the health service they work in. The roles bring many benefits to patients including continuity of care, access to expertise, improved clinical outcomes, and an excellent relationship between patient and healthcare professional. Another area of benefit is the accessibility and completeness of the services provided."
In its election manifesto, the RCN is calling for every patient with a long-term condition to have guaranteed access to specialist nursing care.
Notes
The study findings will be presented at the RCN Annual Congress 2010 fringe event "Capturing the essence and demonstrating the value of clinical nurse specialists" at 5:45pm on Monday 26th April 2010.
The study used Pandora, a software-based modelling tool, to record the complex activity of clinical specialist nurses working in the field of rheumatology between March 2009 and March 2010. It recorded the work of 99 rheumatology specialist nurses spread across the four countries of the UK.
Specialist nurses are dedicated clinical experts who are able to spend time with patients with a particular condition, and help them with everything from drug treatments to exercise plans, and help to ensure that patients have the highest possible quality of life.
Source
Royal College of Nursing (RCN)
Method To Dampen Immune Response Holds Promise For Treatment Of Cancer, Autoimmune Diseases, Transplant Rejection
National Jewish Health has been issued a US patent claiming a method to desensitize B cells by inactivating antigen receptors on their surfaces. The method, discovered by John Cambier, PhD, Chairman of the Integrated Department of Immunology at National Jewish Health, holds promise for treatment of B-cell mediated diseases, such as lymphoma and leukemia, rheumatoid arthritis, lupus and rejection of organ transplants. This therapeutic approach has the potential advantage of inactivating B cells instead of killing them as current treatments do. Therefore, this potential therapy could be more rapidly adjusted in response to the changing needs of patients.
B cells are a crucial part of the adaptive immune response, responsible for making antibodies that can neutralize and destroy pathogens. Several diseases, however, are associated with malfunction of B cells. For example, B cells can turn cancerous in diseases such as lymphoma and leukemia. In autoimmune diseases, such as rheumatoid arthritis or lupus, B cells turn against their own bodies and attack their tissues. B cells can also attack transplanted organs, which they recognize as foreign and potentially harmful.
The recently issued patent describes a method to inactivate B cells by disassembling their B-cell receptors. B cells begin producing antibodies after their B-cell receptors encounter foreign protein fragments, known as antigens. The B-cell receptor contains two distinct subunits; a receptor, which engages antigens, and a transducer, which transmits an activating signal to the interior of the cell.
About a decade ago, Dr. Cambier's laboratory, discovered that the two subunits could be separated, which disables the B cell's ability to recognize antigens and produce antibodies. In 2003, National Jewish Health received a patent (#6,503,509) for this method of B -cell desensitization. The most recent patent (#7,825,224) related to this technology claims the use of antibodies that bind to the transducer subunit of the receptor to inactivate the B cell.
Dr. Cambier's laboratory has recently developed several antibodies against one of the transducer elements, CD79, that have already yielded promising results.
"In contrast to current therapies for B-cell diseases, this method does not kill B cells, it merely inactivates them," said Dr. Cambier. "That could potentially allow for greater flexibility in using a therapy that is developed with this technology. Instead of the months to years it sometimes takes for the effects of current therapy to wane, our method could be reversed within days."
Dr. Cambier has recently received research funding from the State of Colorado and National Jewish Health through the Bioscience Discovery Evaluation Grant Program to further develop this promising technology.
"This research funding underlines our commitment to promote the translation of our scientists' research findings into therapeutic or diagnostic products that can ultimately help patients worldwide," said Emmanuel Hilaire, PhD, Manager of the Technology Transfer Office at National Jewish Health. "National Jewish is currently exploring various commercialization venues for its licensing, including the creation of a start-up company in Colorado."
Source:
William Allstetterx
National Jewish Health
B cells are a crucial part of the adaptive immune response, responsible for making antibodies that can neutralize and destroy pathogens. Several diseases, however, are associated with malfunction of B cells. For example, B cells can turn cancerous in diseases such as lymphoma and leukemia. In autoimmune diseases, such as rheumatoid arthritis or lupus, B cells turn against their own bodies and attack their tissues. B cells can also attack transplanted organs, which they recognize as foreign and potentially harmful.
The recently issued patent describes a method to inactivate B cells by disassembling their B-cell receptors. B cells begin producing antibodies after their B-cell receptors encounter foreign protein fragments, known as antigens. The B-cell receptor contains two distinct subunits; a receptor, which engages antigens, and a transducer, which transmits an activating signal to the interior of the cell.
About a decade ago, Dr. Cambier's laboratory, discovered that the two subunits could be separated, which disables the B cell's ability to recognize antigens and produce antibodies. In 2003, National Jewish Health received a patent (#6,503,509) for this method of B -cell desensitization. The most recent patent (#7,825,224) related to this technology claims the use of antibodies that bind to the transducer subunit of the receptor to inactivate the B cell.
Dr. Cambier's laboratory has recently developed several antibodies against one of the transducer elements, CD79, that have already yielded promising results.
"In contrast to current therapies for B-cell diseases, this method does not kill B cells, it merely inactivates them," said Dr. Cambier. "That could potentially allow for greater flexibility in using a therapy that is developed with this technology. Instead of the months to years it sometimes takes for the effects of current therapy to wane, our method could be reversed within days."
Dr. Cambier has recently received research funding from the State of Colorado and National Jewish Health through the Bioscience Discovery Evaluation Grant Program to further develop this promising technology.
"This research funding underlines our commitment to promote the translation of our scientists' research findings into therapeutic or diagnostic products that can ultimately help patients worldwide," said Emmanuel Hilaire, PhD, Manager of the Technology Transfer Office at National Jewish Health. "National Jewish is currently exploring various commercialization venues for its licensing, including the creation of a start-up company in Colorado."
Source:
William Allstetterx
National Jewish Health
Recent Findings Suggest Need For New Approach To Fighting Disease, Says Dr. Jon J. Kabara
Microorganisms may be the origin behind many diseases when certain circumstances are present, according to new research findings, and often without noticeable infection. Experts believe pathogenic viruses, bacteria, yeasts, and fungi can cause clinical inflammatory problems resulting from low-grade infections that may go unnoticed. These new findings, according to Dr. Jon J. Kabara, require a whole new approach to disease chemotherapy. Med-Chem Labs Inc. is using an approach that eliminates the cause (microorganisms) while relieving the effect (inflammation). A naturally derived food nutrient from mother's milk is currently under investigation to promote health and well being.
The following diseases and conditions have a possible inflammatory component:
- Cardiovascular events
- Atherosclerosis
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Fibromyalgia
- Psoriasis
- Rheumatoid arthritis
The more scientists learn about these and other serious diseases, the more pathologies are being linked with the long-term effects of infection/inflammation in the body. The inflammation-disease connection has become a hot research topic that is expected to explode soon. The therapeutic approach by Med-Chem Labs Inc. is to work with health professionals using a natural fat found in mother's milk that has multiple functional properties (anti-inflammatory/ antimicrobial/immune booster agents). The use of a food grade nutrient is to promote health and self-healing rather than drug treatment.
While confirmation of this hypothesis is currently being investigated in the United States, dermatology studies are now being conducted in the Philippines. Said Obama, the United States President's uncle, has also started research on HIV in Kenya using this food grade nutrient.
Dr. Kabara was the first to pursue the unique health benefits of Lauricidin®, which has now been extensively tested in university, government (CDC), and medical laboratories. As a result, his initial findings have been confirmed by many and reported in peer reviewed scientific journals, books, and patents. Through advanced technology, this natural substance is now available from Med-Chem Laboratories in 95% pure pearlized form.
Source
Med-Chem Laboratories Inc.
The following diseases and conditions have a possible inflammatory component:
- Cardiovascular events
- Atherosclerosis
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Fibromyalgia
- Psoriasis
- Rheumatoid arthritis
The more scientists learn about these and other serious diseases, the more pathologies are being linked with the long-term effects of infection/inflammation in the body. The inflammation-disease connection has become a hot research topic that is expected to explode soon. The therapeutic approach by Med-Chem Labs Inc. is to work with health professionals using a natural fat found in mother's milk that has multiple functional properties (anti-inflammatory/ antimicrobial/immune booster agents). The use of a food grade nutrient is to promote health and self-healing rather than drug treatment.
While confirmation of this hypothesis is currently being investigated in the United States, dermatology studies are now being conducted in the Philippines. Said Obama, the United States President's uncle, has also started research on HIV in Kenya using this food grade nutrient.
Dr. Kabara was the first to pursue the unique health benefits of Lauricidin®, which has now been extensively tested in university, government (CDC), and medical laboratories. As a result, his initial findings have been confirmed by many and reported in peer reviewed scientific journals, books, and patents. Through advanced technology, this natural substance is now available from Med-Chem Laboratories in 95% pure pearlized form.
Source
Med-Chem Laboratories Inc.
Old Antibiotic May Find New Life As A Stroke Treatment
An old intravenous antibiotic may have new life as a stroke treatment, researchers say.
Minocycline appears to reduce stroke damage in multiple ways - inhibiting white blood cells and enzymes that, at least acutely, can destroy brain tissue and blood vessels, respectively, says Dr. David Hess, chair of the Department of Neurology in the Medical College of Georgia School of Medicine. The broad-spectrum antibiotic also seems to reduce cell suicide in the minutes and hours following a stroke, enabling more cells to recover.
He and other researchers leading a clinical trial that will study the drug in 60 stroke patients in Georgia, Kentucky and Oregon say they believe the antibiotic will be a safe, effective adjunct therapy for tPA, the only FDA-approved drug therapy for strokes.
"It's a safe drug that is easy to give and tolerate, that gets into the brain well, and may reduce bleeding, the primary side effect of tPA," says Dr. Hess, principal investigator on the $1.8 million National Institute of Neurological Disorders and Stroke-funded clinical trial. "We think it will make strokes smaller and patient outcomes better."
Their animal studies have shown the drug, given within six hours of a stroke, then every 12 hours for up to three days - the peak time of inflammation - reduces stroke damage by up to 40 percent.
"We know it's safe in humans and we know the concentrations we need to see improvement in the brains of rats can be achieved safely in humans," says Dr. Susan C. Fagan, professor of pharmacy at the University of Georgia, assistant dean for the MCG program of the UGA College of Pharmacy and study co-investigator. "That's an important consideration."
The drug's safety and optimal stroke dose are the primary focus of the phase-one clinical trial in stroke patients who arrive at MCG, University of Kentucky or Oregon Health & Science University within six hours of symptom onset and with measurable neurological symptoms. Every study patient will get one of four doses, starting with 200 milligrams, the most common dose already used, and increasing incrementally up to 700 milligrams. They'll get half their first dose at subsequent 12-hour intervals for a three-day period then be followed for 90 days.
"We are going to be drawing samples from patients to make sure we achieve the concentrations that we want in the blood, plus we want to define the half-life in stroke patients to see if it's different than in the younger patients who take it for other reasons,' says Dr. Fagan. Newer intravenous antibiotics have replaced minocycline in the United States, but an oral version is used to treat conditions such as acne and rheumatoid arthritis. "If the half-life is longer, we can give it less frequently. We are really fine-tuning the dose," she says. They'll do this by looking in the blood for biomarkers, indicators of inflammation, to see if inflammatory factors go up after three days. "It may give us a clue we should treat patients longer," says Dr. Fagan, a co-investigator on the studies leading to minocycline's use in rheumatoid arthritis.
One way minocycline fights inflammation is by inhibiting microglial cells, white blood cells activated by a stroke, says Dr. Hess. "When they get activated, they get angry and produce materials that damage the brain. The inflammatory cascade is bad and good. Early on it's bad, later on it may actually do some good things," he says. Typically these microglial cells are sentinel immune cells for the brain, helping eliminate infections and secreting factors that support neurons. However, acutely in a stroke, brain tissue can become their target. "They are basically cleaning house at first, then later, they are supportive, releasing growth factors and promoting the growth of new blood vessels," adds Dr. Fagan.
Minocycline also blocks matrix metallo-proteinases, also released during stroke, which destroy the basement membrane of blood vessels. The presence of these enzymes also is a mixed bag. "If you want angiogenesis - you want to make new blood vessels - you need MMPs around to get rid of the old ones, like tearing down an old building to build a new one," says Dr. Hess. However, in patients lucky enough to get the clot buster tPA, the enzyme increases the major risk factor: bleeding. Dr. Hess notes that while this initial clinical trial is in ischemic strokes, he thinks minocycline also may be useful in hemorrhagic strokes, which account for about 12 percent of strokes, where clearly blocking MMPs would come in handy.
Minocycline also works by blocking apoptosis, or cell suicide, an observation originally made by MCG Cell Biologist Zheng Dong. "It does this by increasing a protein called bcl-2, which helps cells survive," says Dr. Hess.
The antibiotic's potential usefulness in protecting brain cells began surfacing in scientific literature within the last few years. "It was so interesting to us because we knew that a lot of the limitations of other drugs that had been tried in rodents but didn't work in stroke patients were that they didn't cross into the brain," Dr. Fagan says. "We knew that minocycline did based on previous experiments and the fact that many people who take it for acne or rheumatoid arthritis get dizzy. So we were encouraged by this.
"We wanted something we could give at least three hours after stroke or later. In our studies in animal models, we found at delayed time intervals it was profoundly neuroprotective," says Dr. Fagan. "We studied it at multiple time points at multiple doses and, in fact, some of the most important work we did was finding out how the rodent dose really could be translated to humans," she says, referencing work published in Experimental Neurology in 2004.
For the clinical trial, Wyeth Pharmaceuticals will make the sterile powder used for injection available from Japan, where it's still in use.
At MCG, Dr. Hess as well as MCG Neurologists Chris Hall, Fenwick Nichols and Jeff Switzer are enrolling patients in the study. Other MCG contributors include Biostatistician Jennifer Waller and Physiologist Adviye Ergul.
Source: Toni Baker
Medical College of Georgia
Minocycline appears to reduce stroke damage in multiple ways - inhibiting white blood cells and enzymes that, at least acutely, can destroy brain tissue and blood vessels, respectively, says Dr. David Hess, chair of the Department of Neurology in the Medical College of Georgia School of Medicine. The broad-spectrum antibiotic also seems to reduce cell suicide in the minutes and hours following a stroke, enabling more cells to recover.
He and other researchers leading a clinical trial that will study the drug in 60 stroke patients in Georgia, Kentucky and Oregon say they believe the antibiotic will be a safe, effective adjunct therapy for tPA, the only FDA-approved drug therapy for strokes.
"It's a safe drug that is easy to give and tolerate, that gets into the brain well, and may reduce bleeding, the primary side effect of tPA," says Dr. Hess, principal investigator on the $1.8 million National Institute of Neurological Disorders and Stroke-funded clinical trial. "We think it will make strokes smaller and patient outcomes better."
Their animal studies have shown the drug, given within six hours of a stroke, then every 12 hours for up to three days - the peak time of inflammation - reduces stroke damage by up to 40 percent.
"We know it's safe in humans and we know the concentrations we need to see improvement in the brains of rats can be achieved safely in humans," says Dr. Susan C. Fagan, professor of pharmacy at the University of Georgia, assistant dean for the MCG program of the UGA College of Pharmacy and study co-investigator. "That's an important consideration."
The drug's safety and optimal stroke dose are the primary focus of the phase-one clinical trial in stroke patients who arrive at MCG, University of Kentucky or Oregon Health & Science University within six hours of symptom onset and with measurable neurological symptoms. Every study patient will get one of four doses, starting with 200 milligrams, the most common dose already used, and increasing incrementally up to 700 milligrams. They'll get half their first dose at subsequent 12-hour intervals for a three-day period then be followed for 90 days.
"We are going to be drawing samples from patients to make sure we achieve the concentrations that we want in the blood, plus we want to define the half-life in stroke patients to see if it's different than in the younger patients who take it for other reasons,' says Dr. Fagan. Newer intravenous antibiotics have replaced minocycline in the United States, but an oral version is used to treat conditions such as acne and rheumatoid arthritis. "If the half-life is longer, we can give it less frequently. We are really fine-tuning the dose," she says. They'll do this by looking in the blood for biomarkers, indicators of inflammation, to see if inflammatory factors go up after three days. "It may give us a clue we should treat patients longer," says Dr. Fagan, a co-investigator on the studies leading to minocycline's use in rheumatoid arthritis.
One way minocycline fights inflammation is by inhibiting microglial cells, white blood cells activated by a stroke, says Dr. Hess. "When they get activated, they get angry and produce materials that damage the brain. The inflammatory cascade is bad and good. Early on it's bad, later on it may actually do some good things," he says. Typically these microglial cells are sentinel immune cells for the brain, helping eliminate infections and secreting factors that support neurons. However, acutely in a stroke, brain tissue can become their target. "They are basically cleaning house at first, then later, they are supportive, releasing growth factors and promoting the growth of new blood vessels," adds Dr. Fagan.
Minocycline also blocks matrix metallo-proteinases, also released during stroke, which destroy the basement membrane of blood vessels. The presence of these enzymes also is a mixed bag. "If you want angiogenesis - you want to make new blood vessels - you need MMPs around to get rid of the old ones, like tearing down an old building to build a new one," says Dr. Hess. However, in patients lucky enough to get the clot buster tPA, the enzyme increases the major risk factor: bleeding. Dr. Hess notes that while this initial clinical trial is in ischemic strokes, he thinks minocycline also may be useful in hemorrhagic strokes, which account for about 12 percent of strokes, where clearly blocking MMPs would come in handy.
Minocycline also works by blocking apoptosis, or cell suicide, an observation originally made by MCG Cell Biologist Zheng Dong. "It does this by increasing a protein called bcl-2, which helps cells survive," says Dr. Hess.
The antibiotic's potential usefulness in protecting brain cells began surfacing in scientific literature within the last few years. "It was so interesting to us because we knew that a lot of the limitations of other drugs that had been tried in rodents but didn't work in stroke patients were that they didn't cross into the brain," Dr. Fagan says. "We knew that minocycline did based on previous experiments and the fact that many people who take it for acne or rheumatoid arthritis get dizzy. So we were encouraged by this.
"We wanted something we could give at least three hours after stroke or later. In our studies in animal models, we found at delayed time intervals it was profoundly neuroprotective," says Dr. Fagan. "We studied it at multiple time points at multiple doses and, in fact, some of the most important work we did was finding out how the rodent dose really could be translated to humans," she says, referencing work published in Experimental Neurology in 2004.
For the clinical trial, Wyeth Pharmaceuticals will make the sterile powder used for injection available from Japan, where it's still in use.
At MCG, Dr. Hess as well as MCG Neurologists Chris Hall, Fenwick Nichols and Jeff Switzer are enrolling patients in the study. Other MCG contributors include Biostatistician Jennifer Waller and Physiologist Adviye Ergul.
Source: Toni Baker
Medical College of Georgia
Genes That Increase Rheumatoid Arthritis Risk Identified By Researchers
Researchers in the United States and Sweden have identified a genetic region associated with increased risk of rheumatoid arthritis (RA), a chronic and debilitating inflammatory disease of the joints that affects an estimated 2.1 million Americans. The U.S. arm of the study involved a long-time collaboration between intramural researchers of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other organizations. NIAMS is one of 27 institutes and centers at the National Institutes of Health. The results appeared in the New England Journal of Medicine.
Using the relatively new genome-wide association approach -- which makes it possible to analyze between 300,000 and 500,000 single nucleotide polymorphisms (SNPs, or small differences in DNA that are distributed throughout a person's genetic code) -- researchers in both countries searched for genetic differences in blood samples from people with RA compared to controls. The U.S. group compared 908 samples from patients provided by the North American Rheumatoid Arthritis Consortium (NARAC) -- a group of investigators working together to identify the genetic factors that contribute to RA -- with those from 1,282 people without RA (controls). The Swedish group compared 676 samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) with 673 controls.
Both groups' searches led them to a region of chromosome 9 containing two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5).
"The whole-genome screening method lets us identify genes that contribute to disease-susceptibility without imposing our preconceived notions of the disease. We expected to come up with something new," says Elaine F. Remmers, Ph.D., of the Genetics and Genomics Branch of the NIAMS Intramural Research Program and an author of the study. "We were thrilled to find out that TRAF1-C5 showed association not only in the samples that we did with NARAC but also independently in the Swedish group. By combining our information, we were able to make a much stronger case [for a TRAF1-C5 association]. The combined evidence was pretty impressive."
Remmers says the TRAF1-C5 region was the third of three major susceptibility chromosomal regions for RA identified by their whole genome screen. The first two, HLA-DRB1 and PTPN22, had already been well established.
She says that it's not yet known how the genes in the TRAF1-C5 region influence RA risk. Nor can scientists say which of the two genes is causing the disease. "Actually, both genes are very interesting candidates," she says. "They both control inflammatory processes that really are relevant for the disease, so we could easily envision either of them playing a role -- or both."
The hope is that by learning more about the genes and their role in the disease, scientists may find clues to influencing treatment of the disease. "We are hoping that we will find variants in either of the genes that will lead us to new targets for therapy. Once we understand how the RA-associated variants work, we may be able interfere with the pathways the variants are influencing and either prevent the disease or block its progression."
According to coauthor Daniel Kastner, M.D., Ph.D., NIAMS clinical director and chief of the NIAMS Genetics and Genomics Branch, "The success of the study can be attributed in part to the productive, longstanding collaboration between NIAMS intramural researchers and other scientists that the Institute supports around the country." NARAC was established 10 years ago by coauthor Peter K. Gregersen, M.D., at the Feinstein Institute for Medical Research, the North Shore Long Island Jewish Health System, in order to facilitate the collection and analysis of RA genetic samples. Kastner was also a key early member of the NARAC, as were many other investigators at several academic health centers across the United States.
In addition to NIAMS, other support for the U.S. study came from the National Center for Research Resources, the Arthritis Foundation, grants from the Boas Family and the Eileen Ludwig Greenland Center for Rheumatoid Arthritis (Feinstein Institute for Medical Research), the Rosalind Russell Medical Research Center for Arthritis and the Kirkland Scholar Award (University of California, San Francisco).
Support for the Swedish arm of the study came from the Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, the King Gustaf V's 80-Year Foundation, the Swedish Rheumatism Foundation, the Stockholm County Council, the AFA insurance company and the Agency for Science Technology and Research, Singapore.
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 Center for Research Resources (NCRR) provides clinical and translational researchers with the training and tools they need to understand, detect, treat, and prevent a wide range of diseases. For more information about NCRR visit ncrr.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/.
Reference: Plenge RM et al. TRAF1-C5 as a risk locus for rheumatoid arthritis -- a genomewide study. NEJM 2007;357:1199 -1209.
Source: Trish Reynolds
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Using the relatively new genome-wide association approach -- which makes it possible to analyze between 300,000 and 500,000 single nucleotide polymorphisms (SNPs, or small differences in DNA that are distributed throughout a person's genetic code) -- researchers in both countries searched for genetic differences in blood samples from people with RA compared to controls. The U.S. group compared 908 samples from patients provided by the North American Rheumatoid Arthritis Consortium (NARAC) -- a group of investigators working together to identify the genetic factors that contribute to RA -- with those from 1,282 people without RA (controls). The Swedish group compared 676 samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) with 673 controls.
Both groups' searches led them to a region of chromosome 9 containing two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5).
"The whole-genome screening method lets us identify genes that contribute to disease-susceptibility without imposing our preconceived notions of the disease. We expected to come up with something new," says Elaine F. Remmers, Ph.D., of the Genetics and Genomics Branch of the NIAMS Intramural Research Program and an author of the study. "We were thrilled to find out that TRAF1-C5 showed association not only in the samples that we did with NARAC but also independently in the Swedish group. By combining our information, we were able to make a much stronger case [for a TRAF1-C5 association]. The combined evidence was pretty impressive."
Remmers says the TRAF1-C5 region was the third of three major susceptibility chromosomal regions for RA identified by their whole genome screen. The first two, HLA-DRB1 and PTPN22, had already been well established.
She says that it's not yet known how the genes in the TRAF1-C5 region influence RA risk. Nor can scientists say which of the two genes is causing the disease. "Actually, both genes are very interesting candidates," she says. "They both control inflammatory processes that really are relevant for the disease, so we could easily envision either of them playing a role -- or both."
The hope is that by learning more about the genes and their role in the disease, scientists may find clues to influencing treatment of the disease. "We are hoping that we will find variants in either of the genes that will lead us to new targets for therapy. Once we understand how the RA-associated variants work, we may be able interfere with the pathways the variants are influencing and either prevent the disease or block its progression."
According to coauthor Daniel Kastner, M.D., Ph.D., NIAMS clinical director and chief of the NIAMS Genetics and Genomics Branch, "The success of the study can be attributed in part to the productive, longstanding collaboration between NIAMS intramural researchers and other scientists that the Institute supports around the country." NARAC was established 10 years ago by coauthor Peter K. Gregersen, M.D., at the Feinstein Institute for Medical Research, the North Shore Long Island Jewish Health System, in order to facilitate the collection and analysis of RA genetic samples. Kastner was also a key early member of the NARAC, as were many other investigators at several academic health centers across the United States.
In addition to NIAMS, other support for the U.S. study came from the National Center for Research Resources, the Arthritis Foundation, grants from the Boas Family and the Eileen Ludwig Greenland Center for Rheumatoid Arthritis (Feinstein Institute for Medical Research), the Rosalind Russell Medical Research Center for Arthritis and the Kirkland Scholar Award (University of California, San Francisco).
Support for the Swedish arm of the study came from the Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, the King Gustaf V's 80-Year Foundation, the Swedish Rheumatism Foundation, the Stockholm County Council, the AFA insurance company and the Agency for Science Technology and Research, Singapore.
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 Center for Research Resources (NCRR) provides clinical and translational researchers with the training and tools they need to understand, detect, treat, and prevent a wide range of diseases. For more information about NCRR visit ncrr.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/.
Reference: Plenge RM et al. TRAF1-C5 as a risk locus for rheumatoid arthritis -- a genomewide study. NEJM 2007;357:1199 -1209.
Source: Trish Reynolds
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Subchondral Bone Changes Contribute To Cartilage Damage And Loss
A recent study determined that bone area predicted the development of medial (inner side) and lateral (outer side) knee cartilage damage and loss of medial cartilage volume. Subchondral bone mineral density (BMD) was associated with medial defect development but not cartilage loss. Researchers believe subchondral bone changes and loss of cartilage contribute to the development of osteoarthritis (OA). Read details of the study online or in the July issue of Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology.
According to a report by the World Health Organization (WHO), 9.6% of men and 18% of women over 60 years of age worldwide have OA symptoms, making it a leading cause of disability. OA is caused by the gradual loss of cartilage and underlying bone, typically affecting the knee, hip, hand, and spine joints. The Centers for Disease Control and Prevention estimate that 4.3 million Americans over age 60 have symptomatic knee OA, the most common joint affected. In fact prior studies of U.S. and European populations (over 45 years of age) show higher rates of knee OA in 14.1% of men and 22.8% of women (WHO report).
Ph.D. candidate and lead author of the study, Dawn Dore??, enrolled 341 participants in their prospective study. Participants had a mean age of 63 years and provided measurements of tibial knee cartilage volume, cartilage defects, and bone area using magnetic resonance imaging (MRI). The tibial subchondral BMD was determined using dual x-ray absorptiometry (DXA). Follow-up measurements of cartilage volume and defects were taken 2.7 years later.
Study results found that baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 and OR 2.4 per 1 SD increase, respectively). Cartilage volume loss at the medial tibial site was also positively predicted by baseline bone area (?? -34.9 per 1 SD increase). However, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase) and was not associated with loss of cartilage.
"Our results clearly show bone area was a predictor of cartilage defect development in the inner and outer knee, as well as medial cartilage volume loss," said Ms. Dore??. "We found that subchondral BMD only predicted defect development on the inside of the knee, but not cartilage loss". Researchers noted that the associations were independent of each other and suggest there are multiple mechanisms where changes in subchondral bone could lead to cartilage damage. "With the ability to predict those at risk of developing knee OA, early interventions can be offered to patients in order to lessen the disabling affects of this disease," concluded Ms. Dore??.
Source: Wiley - Blackwell
According to a report by the World Health Organization (WHO), 9.6% of men and 18% of women over 60 years of age worldwide have OA symptoms, making it a leading cause of disability. OA is caused by the gradual loss of cartilage and underlying bone, typically affecting the knee, hip, hand, and spine joints. The Centers for Disease Control and Prevention estimate that 4.3 million Americans over age 60 have symptomatic knee OA, the most common joint affected. In fact prior studies of U.S. and European populations (over 45 years of age) show higher rates of knee OA in 14.1% of men and 22.8% of women (WHO report).
Ph.D. candidate and lead author of the study, Dawn Dore??, enrolled 341 participants in their prospective study. Participants had a mean age of 63 years and provided measurements of tibial knee cartilage volume, cartilage defects, and bone area using magnetic resonance imaging (MRI). The tibial subchondral BMD was determined using dual x-ray absorptiometry (DXA). Follow-up measurements of cartilage volume and defects were taken 2.7 years later.
Study results found that baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 and OR 2.4 per 1 SD increase, respectively). Cartilage volume loss at the medial tibial site was also positively predicted by baseline bone area (?? -34.9 per 1 SD increase). However, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase) and was not associated with loss of cartilage.
"Our results clearly show bone area was a predictor of cartilage defect development in the inner and outer knee, as well as medial cartilage volume loss," said Ms. Dore??. "We found that subchondral BMD only predicted defect development on the inside of the knee, but not cartilage loss". Researchers noted that the associations were independent of each other and suggest there are multiple mechanisms where changes in subchondral bone could lead to cartilage damage. "With the ability to predict those at risk of developing knee OA, early interventions can be offered to patients in order to lessen the disabling affects of this disease," concluded Ms. Dore??.
Source: Wiley - Blackwell
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