Brain Development Steered By Newly Discovered RNA

How does the brain work? This question is one of the greatest scientific mysteries, and neurobiologists have only recently begun to piece together the molecular building blocks that enable human beings to be “thinking” animals.

One fundamental property of the mammalian brain is that it continues to develop after birth, and one of the biggest drivers of the formation of new links between neurons is experience. Every time a baby sticks her finger on a pin or laughs in response to an adult’s embellished gestures, a cascade of genetic activity is triggered in her brain that results in new, and perhaps even lifelong, synaptic connections.

New research from the lab of Michael Greenberg, Nathan Marsh Pusey professor and chair of neurobiology at HMS, in collaboration with bioinformatics specialist and neuroscientist Gabriel Kreiman, assistant professor of ophthalmology at Children’s Hospital, Boston, has found that a particular set of RNA molecules widely considered to be no more than a genomic oddity are actually major players in brain development – and are essential for regulating the process by which neurons absorb the outside world into their genetic machinery.

“This discovery may inform disorders of cognition such as autism spectrum disorders,” says Greenberg. “It’s incredibly important to know all about the brain’s genetic regulatory mechanisms in order to think more deeply about how to develop therapies for treating these sorts of conditions.”

This research will be published online April 15 in the journal Nature.

For over 25 years, Greenberg and his lab have been unraveling the mechanisms that enable the outside world to have a profound and lasting effect on neuronal genes. Broadly speaking, when a neuron is stimulated by an external excitation (the pin, the gesture), it releases chemicals called neurotransmitters (the most common one is glutamate). This neurotransmitter binds to a receptor on the neuron surface and then sets in motion a chain of events that affects the genetic activity of the cell. This in turn helps to modify the synaptic connections between neurons, which are the basis of learning and memory.

But what exactly happens inside of a cell after it is activated by neurotransmitter release?

To get closer to the cellular action, Tae-Kyung Kim and Jesse Gray of the Greenberg lab, in collaboration with Martin Hemberg from the Kreiman lab at Children’s, used two kinds of high-throughput, next-generation sequencing technologies, RNA-Seq and CHIP-Seq.

Working with mouse brain cells in culture, the researchers used RNA-Seq to identify, with great sensitivity, the RNA sequences that are newly synthesized when a neuron is stimulated in a manner that mimics the effect of a neurotransmitter, and which in turn touches off a domino-like cascade of intracellular signals. The researchers were then able to identify, sequence and – using CHIP-Seq – establish the genomic “address” and the regulatory factors that control the expression of all the genes switched on in these brain cells by the stimulus.

They discovered that there were individual and disparate stretches of DNA that appeared to be amplifying the genes’ activity, escalating the process of messenger RNA and protein production. These bits of DNA, called “enhancer regions,” were more often than not targeting their genes over vast genomic distances, like a computer dictating orders to a global digital network via satellite.

Most important, however, was the discovery that these enhancer regions accomplished this phenomenon by producing their own RNA molecules, and that these enhancer RNAs, or eRNAs, were intensifying the enzymatic processes that are essential for a gene’s ability to create protein.

“Biologists have known about enhancers since 1980, and there has even been a paper or two describing RNA produced at enhancer regions, but it was largely considered an isolated curiosity,” says Greenberg. “What we’ve discovered here is how widespread this phenomenon is. We’ve found that there are thousands of these enhancers, that they’re spread throughout the genome, and that they are essential to the process in which experience results in new synaptic connections. What’s more, we suspect that they’re active in many other mammalian cell types, not just neurons.”

It isn’t clear yet precisely how these eRNAs accomplish their synaptic-building tasks, or even where they travel to within the neuron once they are produced. These are questions for further study. Still, the researchers believe there is a likelihood that these finding may eventually prove relevant to, and cast light on, our understanding of certain neurological and psychiatric disorders in which the regulation of gene activity plays a critical role.

This research was funded by the National Institutes of Health.

David Cameron

Full Citation:
Nature, April 14, 2010, early online publication

Widespread transcription at neuronal activity-regulated enhancers

Tae-Kyung Kim1*{, Martin Hemberg2*, Jesse M. Gray1*, Allen M. Costa1, Daniel M. Bear1, Jing Wu3,
David A. Harmin1,4, Mike Laptewicz1, Kellie Barbara-Haley5, Scott Kuersten6, Eirene Markenscoff-Papadimitriou1{, Dietmar Kuhl7, Haruhiko Bito8, Paul F. Worley3, Gabriel Kreiman2 & Michael E. Greenberg1

1-Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
2-Department of Ophthalmology, Children’s Hospital Boston, Center for Brain Science and Swartz Center for Theoretical Neuroscience, Harvard University, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
3-The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
4-Children’s Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
5-Molecular Genetics Core facility, Children’s Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
6-Epicentre Biotechnologies, 726 Post Road, Madison, Wisconsin 53713, USA.
7-Institute for Molecular and Cellular Cognition (IMCC), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany.
8-Department of Neurochemistry, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. {Present addresses: University of Texas Southwestern Medical Center, Department of Neuroscience, 5323 Harry Hines Blvd, Dallas, Texas 75390-9111, USA (T.-K.K.); Graduate Program in Neuroscience, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94123, USA (E.M.-P.).

David Cameron
Harvard Medical School

Mesothelioma-Data Highlights Recent Mesothelioma Case

Four men from Texas are suing Chevron and Gulf Oil on behalf of their father who died recently of mesothelioma which is a cancer caused by asbestos exposure.

Kyle, Dan, Ted and Mark Bergeron claim that their father Gliese Bergeron’s disease was wrongfully caused. Gliese Bergeron died of mesothelioma on October 22, 2008.

According to the lawsuit filed Dec. 22 in Jefferson County District Court, Gliese Bergeron worked as a pipefitter, operator, truck driver, insulator and maintenance planner at Chevron and Gulf Oil from 1942 to 1983.

Bergeron’s sons argue that their father’s exposure to asbestos was foreseeable and should have been anticipated by the defendants.

The lawsuit states that Chevron and Gulf Oil were allegedly negligent as they failed to test the air in order to find out the levels of asbestos fibers at the work site and also to warn their employees regarding the health hazards associated to asbestos exposure.

According to the suit, Chevron and Gulf Oil allegedly failed to implement proper safety measures to protect workers, to perform appropriate industrial hygiene monitoring, to adequately train, educate and instruct workers on the risks of asbestos and allegedly failed to provide and suggest the use of personal protective equipment to guard workers.

The complaint also states that both the companies allegedly failed to implement and recommend engineering controls to minimize workers’ exposure to asbestos, failed to rule out improper handling of asbestos fibers, to provide workers with a safe area to work and to develop and implement an occupational medicine program to monitor workers’ exposure to asbestos in a timely manner.

Judge Gary Sanderson of 60th District Court will be hearing the case.

Case No. B182-900

This news release was mesothelioma-data. We have extensive information on Mesothelioma, asbestos and lung cancer. Please visit our website for more information.


News From The American Journal Of Pathology, 25-Mar-2009

Tracking Acute Kidney Injury

Dr. Eisei Noiri and colleagues at the University of Tokyo, Japan identified a novel biomarker to monitor acute kidney injury. They present their data in the April 2009 issue of The American Journal of Pathology.

Acute kidney injury may be reversible if treated promptly and appropriately. Novel biomarkers therefore need to be developed to identify injury at early time points as well as to estimate the severity of the damage.

Negishi et al examined whether levels of urinary L-type fatty acid-binding protein (L-FABP), a protein found in the kidney that is secreted in the urine upon kidney injury, could be used to monitor acute kidney injury. Levels of L-FABP correlated with the level of acute kidney injury at significantly earlier time points than levels of conventional renal markers such as blood urea nitrogen (BUN) or urinary N-acetyl-D-glucosaminidase (NAG). In addition, L-FABP showed better correlation than BUN or NAG with final histological injury scores, especially at early time points.

L-FABP thus represents a better choice than conventional renal markers for evaluating early acute kidney injury. Future studies will “evaluat[e] various human AKI populations ??¦ to confirm the significance of urinary L-FABP as a forecasting biomarker of pathological and functional damage.”

Negishi K, Noiri E, Doi K, Maeda R, Sugaya T, Portilla D, Fujita T : Monitoring of urinary L-type fatty acid binding protein predicts histological severity of acute kidney injury.
Am J Pathol 2009, 174: 1154-1159

New Target for Alzheimer’s Disease Therapy

Researchers at the VU University Medical Center, Amsterdam and the University of Amsterdam, The Netherlands discovered that the unfolded protein response contributes to nerve cell death in Alzheimer’s Disease. This report can be found in the April 2009 issue of The American Journal of Pathology.

Alzheimer’s disease is an incurable, degenerative, terminal form of dementia, thought to be caused in part by the presence of “tangles” of misfolded proteins. The unfolded protein response protects cells from the toxic effects of accumulated misfolded proteins; however, prolonged activation of the unfolded protein response, such as in Alzheimer’s disease, may lead to cell death.

Hoozemans et al hypothesized that the unfolded protein response contributed to neurodegeneration in Alzheimer’s disease partially though its effects on the accumulation of hyperphosphorylated tau, a major component of tangles in Alzheimer’s disease patients. They found that markers of the unfolded protein response were expressed in areas of tau accumulation in patients with Alzheimer’s disease. These unfolded protein response-related proteins were expressed early, in pre-tangle neurons, but were absent in tangle neurons.

This report suggests that “unfolded protein response activation occurs at an early stage of neurofibrillary degeneration and ??¦ that the prolonged activation of the [unfolded protein response] is involved in both tau phosphorylation and neurodegeration in [Alzheimer's Disease] pathogenesis. ??¦ Future studies will address the therapeutic opportunities of this pathway for the treatment of [Alzheimer's Disease] and other tauopathies.”

Hoozemans JJM, van Haastert ES, Nijholt DAT, Rozemuller AJM, Eikelenboom P, Scheper W: The unfolded protein response is activated in pretangle neurons in Alzheimer’s disease hippocampus.
Am J Patholl 2009, 174: 1241-1251

Bacterial Toxin Leads to Systemic Infection

A group led by Dr. Michael Klapproth at Emory University, Atlanta suggests that bacterial lymphotoxin disrupts intestinal epithelial barrier function. They report these findings in the April 2009 issue of The American Journal of Pathology.

Numerous bacterial species commonly live in the human gut. These bacteria contribute to digestion, but also may cause disease. Some bacteria, such as Escheria coli (E. coli) or Citrobacter rodentium (C. rodentium), can breach the intestinal epithelial barrier, entering the blood and causing systemic infection.

Lymphostatin, a toxin produced by gram negative bacteria including E. coli and C. rodentium, has been associated with bacterial virulence. To determine if lymphostatin affects epithelial barrier integrity, Babbin et al generated two strains of C. rodentium, CrGIM21 and CrPrM5, with different mutations in lymphostatin. Whereas wild-type C. rodentium disrupted epithelial barrier function, CrGIM21 and CrPrM5 had reduced effects on two aspects of epithelial cell function. These data suggest that lymphostatin may be a strong target candidate for treatment of enteric gram negative bacteria.

Dr. Klapporth and colleagues postulate that “therapeutic interventions in form of specific immunoglobulins directed against lymphostatin and its enzymatic activities might provide an attractive alternative to antibiotics in treating intestinal injury and preventing extraintestinal manifestations of Gram negative infection.”

Babbin BA, Sasaki M, Gerner-Schmidt KW, Nusrat A, Klapproth J-M A: The bacterial virulence factor lymphostatin compromises intestinal epithelial barrier function by modulating Rho GTPases.
Am J Pathol 2009, 174: 1347-1357

Mouse Model of Human Psoriasis

Researchers led by Nicole Ward at Case Western Reserve University, Cleveland have developed a new mouse model to study human psoriasis. These findings are presented in the April 2009 issue of The American Journal of Pathology.

Psoriasis is a chronic inflammatory disease that causes red scaly patches to appear on the skin. It is characterized by excessive skin production, formation of new blood vessels, and the presence of white blood cells. Study of psoriasis has been limited, however, due to the absence of a mouse model that adequately reproduces these symptoms.

Over-expression Tie-2, a molecule involved in the formation of new blood vessels, in two types of skin cells, epithelial cells and keratinocytes, has provided the best psoriasis model to date. To determine whether Tie-2 over-expression in epithelial cells or keratinocytes resulted in the psoriasis phenotype, Wolfram et al engineered two new mouse models in which Tie-2 expression was limited to either epithelial cells or keratinocytes. Only the keratinocyte-restricted Tie-2 mice developed symptoms similar to human psoriasis. These symptoms were reduced by treatment with cyclosporin A, a common psoriasis therapy. Keratinocyte-restricted Tie-2 mice, therefore, may serve as an animal model for human psoriasis.

The psoriasis model developed by Dr. Ward’s group “bears a striking resemblance to human psoriasis, meeting multiple criteria at the clinical, histological, biochemical, immunophenotype, and pharmacologic levels ??¦ and therefore will become important for studying pathological mechanisms of psoriasis and pre-clinical testing of new therapeutics.”

Wolfram JA, Diaconu D, Hatala DA, Rastegar J, Knutsen DA, Lowther A, Askew D, Gilliam AC, McCormick TS, Ward NL: Keratinocyte but not endothelial cell specific over-expression of Tie-2 leads to the development of psoriasis.
Am J Pathol 2009, 174: 1443-1458

New Marker for Prostate Cancer Progression

Avraham Raz and colleagues at the University of Michigan have identified a cleaved form of galectin-3 as a marker for prostate cancer progression. These data are presented in the April 2009 issue of The American Journal of Pathology.

Prostate cancer is a common malignancy among men over the age of 50. The stage at which prostate cancer is diagnosed is critical for determining prognosis as well as choosing appropriate therapies.

Decreased expression of the marker galectin-3 has been reported to correlate with neoplastic progression in prostate cancer; however, increased levels of galectin-3 have been linked to tumorigenicity in a number of other tumor types. In order to reconcile this difference, Wang et al hypothesized that galectin-3 was cleaved during prostate cancer progression. They identified cleaved galectin-3 in later stage prostate cancer, and determined that reducing levels of galectin-3 inhibited the development of metastatic prostate cancer. Thus, cleaved galectin-3 may serve as a diagnostic marker and therapeutic target for prostate cancer progression.

Dr. Raz’s group “show[s] that galectin-3 is cleaved during the progression of prostate cancer and might be associated with metastasis, cell growth, and tumorigenicity. ??¦ Expression of intact versus cleaved galectin-3 thus might be used as a marker for prognosis of prostate cancer and a therapeutic target for the treatment of prostate cancer.”

Wang Y, Nangia-Makker P, Tait L, Balan V, Hogan V, Jienta KJ, Raz A: Regulation of prostate cancer progression by galectin-3.
Am J Pathol 2009, 174: 1515-1523


The American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.

Angela Colmone

American Journal of Pathology

Social Behavior Differs In Children With Family History Of Autism

The baby brothers and sisters of autistic children do not seek emotional cues from adults, or respond to them, as often as other toddlers do, suggests new research from the University of California, San Diego.

The study is the first to investigate “social referencing” behavior in children from families at high risk for autism and also points to profound differences in related measurements of brain activity, said lead researcher Leslie Carver.

Carver, an assistant professor of psychology and director of the Developmental Cognitive and Social Neuroscience Lab at UC San Diego, is presenting the findings at the 2007 International Meeting for Autism Research in Seattle, Wash.

“Our results,” Carver said, “support two important ideas about autism: That those behaviors that are diagnostic of the disorder fall on one end of a broad behavioral spectrum and also that there is a strong genetic component to autism, evidenced by the behavioral resemblances in close family members.”

The heritability of autism has been estimated as high as 90 percent, Carver noted, and siblings are at increased risk of receiving the diagnosis themselves: About 8 percent will go on to develop the disorder, as compared to about .5 percent of the general population.

Social referencing involves checking in with the emotional displays of others (especially those we expect to be knowledgeable about a novel situation) and regulating our own emotions and behavior in response. It is something most of us do and do without thinking. On spying a new caterpillar in the park, a young child might turn to find a parent’s smile before toddling over to take a closer look. And an adult, startled by a sudden jolt on an airborne plane, might seek out the expression of a flight attendant to determine whether that was just a nasty bit of turbulence or something really worth worrying about.

Typically, social referencing begins to emerge toward the end of the first year of life. But in individuals with autism, this behavior, along with several other aspects of social cognition, is characteristically impaired.

The current research is in line with earlier work demonstrating that first-degree relatives of autistic children often display milder, or subclinical, features of the disorder.

Carver and her colleagues, UC San Diego psychology professor Karen Dobkins, doctoral student Lauren Cornew and post-doctoral researcher Joseph McCleery, tested 18 high-risk toddlers (18-month-old siblings of children diagnosed with autism) and compared their results to those of 28 age-matched counterparts who had no family history of the disorder.

In the behavioral portion of the experiments, the children were presented with three novel and ambiguous toys – toys that could be taken as either good or bad, scary or fun, or neither – and their caregivers were trained to react with facial expressions and vocal signals that were positive, negative and neutral. The interactions were videotaped and later analyzed.

After the behavioral testing, the children were shown pictures of the same toys and their brain responses were measured – specifically by tracking ERP (event-related potential) activity, or the electrical activity of groups of neurons firing in synchrony in response to a specific event.

The high-risk toddlers differed in almost every element of social referencing, the researchers found: Though they sought emotional information from adults as quickly as the low-risk toddlers, they did so about 30 percent less frequently, and they did not respond to the adult’s information in ways that were consistent with the adult’s reaction.

Brain-activity measurements told a similar story: Where low-risk children showed the expected magnitude of neural response to emotionally tagged objects, the high-risk ones did not. And where the brain activity of low-risk children correlated with their behavior regulation, this pattern was not observed in the high-risk.

“It’s as if the high-risk children do not have as clear an understanding of the meaning of an emotion and don’t connect it to the object in the same way,” Carver said.

Data from children who would later go on to a diagnosis of autism are not included in the study results.

The study is supported by funding from the National Association for Autism Research, Autism Speaks and the MIND Institute at UC Davis.

Contact: Inga Kiderra

University of California – San Diego

First Anti-TNF Biologic Therapy To Treat 1 Million Patients Worldwide

Centocor, Inc., Schering-Plough Corporation, and Mitsubishi Tanabe Pharma Corporation have announced that an estimated one million patients have now been treated with REMICADE® (infliximab), the leading anti-tumor necrosis factor (TNF)-alpha therapy worldwide. In fact, REMICADE has been used to treat more patients worldwide than all other anti-TNF-alpha agents combined. REMICADE was the first anti-TNF-alpha treatment approved by the U.S. Food and Drug Administration (FDA), when it was indicated for the treatment of acute moderate to severe Crohn’s disease in 1998. The indication for Crohn’s disease was quickly followed by additional indications, such as rheumatoid arthritis.

“Rheumatoid arthritis derailed my life,” said Ellen Shmueli, RA patient. “Simple tasks like lifting my child or holding a pen were nearly impossible. It’s hard to put into words what REMICADE has meant to me.”

Through a long line of firsts in the biotechnology industry, the history of REMICADE includes 15 FDA indications spanning across inflammatory diseases that include Crohn’s disease (adult and pediatric), ulcerative colitis, rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis and psoriasis.

“This significant milestone was achieved as a result of nearly three decades of expanding and improving access for people living with life-altering inflammatory diseases,” said Neal Fowler, President, Centocor, Inc. “In partnership with Centocor R&D, we will continue our pledge of bringing the promise of biomedicine to physicians and patients through continued research and development, REMICADE and our promising pipeline portfolio.”

REMICADE has been studied in more than 37 clinical trials, evaluating its use in a wide variety of diseases of the immune system and is approved for use in 88 countries.

“Having been a part of its initial approval in 1998, I have personally witnessed how REMICADE has satisfied unmet therapeutic needs and resulted in significant life-changing improvements in patients,” said Thomas F. Schaible, PhD, Vice President, Medical Affairs, Centocor, Inc. “Almost a decade later, REMICADE continues to positively affect patients’ lives and Centocor continues its commitment to developing novel and important therapies for diseases of the immune system.”

“Around the world, the treatment of patients with inflammatory diseases, such as rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis and Crohn’s disease, has been transformed by the availability of REMICADE,” said Robert J. Spiegel, M.D., chief medical officer and senior vice president, Schering-Plough Research Institute. “Schering-Plough is committed to bringing the benefits of REMICADE, with its proven efficacy and rapid onset of action, to relieve the suffering of patients with these chronic inflammatory conditions.”

Important firsts for REMICADE include:

* In August 1998, REMICADE was approved on an accelerated basis for the acute treatment of moderate-to-severe Crohn’s disease in patients who have had an inadequate response to conventional therapy and fistulizing disease. This approval made REMICADE the first TNF-alpha inhibitor available in the U.S.

* In August 1999, REMICADE became the first TNF-alpha inhibitor approved in the European Union (EU) for the short-term treatment of severe, active Crohn’s disease and fistulizing, active Crohn’s disease in patients who have not responded to conventional therapy.

* In December 2001, REMICADE became the first TNF-alpha inhibitor approved in Japan for the treatment of moderate-to-severe Crohn’s disease.

* In February 2002, REMICADE became the first TNF-alpha inhibitor indicated in the U.S. to improve physical function in patients with moderate to severe RA who have had an inadequate response to methotrexate.

* In June 2002, REMICADE became the first TNF-alpha inhibitor approved by the FDA for maintenance therapy in patients with moderate to severe Crohn’s disease. And in April 2003, it became the first TNF-alpha inhibitor approved for maintenance therapy of fistulising Crohn’s disease.

* In May 2003, REMICADE became the first TNF-alpha inhibitor approved in the EU for the treatment of ankylosing spondylitis in patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy.

* In October 2004, REMICADE became the first TNF-alpha inhibitor approved for the treatment of active and progressive psoriatic arthritis in patients who have responded inadequately to disease modifying anti-rheumatic drug therapy.

* In September 2005, the FDA approved REMICADE as the first and only biologic for reducing signs and symptoms, achieving clinical remission and mucosal healing and eliminating corticosteroid use in adults with moderately to severely active UC who have had an inadequate response to conventional therapy. The FDA extended the indication to include maintenance therapy for UC in October 2006.

* In March 2006, REMICADE became the first biologic therapy approved to treat moderately to severely active UC in the European Union (EU), in patients with an inadequate response to conventional therapy, including corticosteroids and 6-MP or AZA, or those intolerant to or contraindicated for such therapies.

* In May 2006, REMICADE became the first and only biologic indicated to reduce signs and symptoms and induce and maintain clinical remission in pediatric patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.


REMICADE is a monoclonal antibody that specifically targets TNF-alpha, which has been shown to play a role in Crohn’s disease (CD), rheumatoid arthritis (RA), ankylosing spondylitis (AS) psoriatic arthritis (PsA), ulcerative colitis (UC), pediatric Crohn’s disease (PCD) and psoriasis (PsO). REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and the only agent approved globally in the 3 regions of North America, the EU and Japan for the treatment of both RA and CD. Additionally, REMICADE is the only anti-TNF approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology. The safety and efficacy of REMICADE have been well established in clinical trials over the past 15 years and through commercial experience with more than one million patients treated worldwide.

In the U.S., REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA. REMICADE is the only biologic indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active CD who have had an inadequate response to conventional therapy. REMICADE is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing CD. In December 2004, REMICADE was approved for reducing signs and symptoms in patients with active AS. In May 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, in September 2005, REMICADE was approved for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. This approval makes REMICADE the first and only biologic approved for the treatment of moderate to severe UC. In May 2006, REMICADE was approved for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. This approval establishes REMICADE as the first and only biologic therapy approved for the treatment of PCD. In August 2006, REMICADE was approved for inhibiting progression of structural damage and improving physical function in patients with psoriatic arthritis. In September 2006, REMICADE was approved for the treatment of adults with chronic, severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. In October 2006, REMICADE was approved for maintaining clinical remission and mucosal healing in patients with moderately to severely active UC, who have had an inadequate response to conventional therapy.

In the EU, REMICADE is indicated for the treatment of severe, active CD in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. REMICADE also is indicated for the treatment of fistulizing, active CD in patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy).

For RA patients in the EU, REMICADE, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in patients with active disease when the response to disease-modifying drugs, including methotrexate, has been inadequate, and in patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs. In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated. In carefully selected patients with RA who have tolerated three initial two-hour infusions of REMICADE, consideration may be given to administering subsequent infusions over a period of not less than one hour.

In the EU, REMICADE is also indicated for the treatment of AS in patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy. REMICADE is also approved for the treatment of active and progressive PsA in adults when the response to previous disease modifying anti-rheumatic drug therapy has been inadequate. REMICADE should be administered in combination with methotrexate or alone in patients who show intolerance to methotrexate or for whom methotrexate is contraindicated. REMICADE is also approved in the EU for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or have a contraindication to, or are intolerant of other systemic therapy including cyclosporine, methotrexate or PUVA (psoralen plus ultraviolet A light).

In February 2006, REMICADE was approved in the EU for the treatment of moderately to severely active UC in patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-MP or azathioprine, or who are intolerant to or have medical contraindications for such therapies. This approval made REMICADE the first and only biologic therapy approved to treat moderate to severe UC in the EU. In May 2007, REMICADE was indicated for the treatment of severe, active Crohn’s disease, in pediatric patients aged 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications for such therapies. REMICADE has been studied only in combination with conventional immunosuppressive therapy

REMICADE is available in an IV form. REMICADE is actually a powder to be reconstituted as a solution for IV infusion. Unlike self-administered therapies that require patients to inject themselves frequently, REMICADE is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting. In RA (3 mg/kg), CD (5 mg/kg), PsA (5 mg/kg), UC (5 mg/kg), PCD (5 mg/kg), and PsO (5 mg/kg), REMICADE is a two-hour infusion administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients may require as few as six treatments each year. In AS (5 mg/kg), REMICADE is a two-hour infusion administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6.

Centocor discovered REMICADE and has exclusive marketing rights to the product in the United States.

Schering-Plough markets REMICADE in all countries outside of the United States, except in Japan, China and parts of the Far East. In China, Xian-Janssen markets REMICADE. In Japan and other parts of the Far East, Mitsubishi Tanabe Pharma Corporation markets the product.

Important Safety Information

There are reports of serious infections, including tuberculosis (TB), sepsis and pneumonia. Some of these infections have been fatal. Tell your doctor if you have had recent or past exposure to people with TB. Your doctor will evaluate you for TB and perform a TB test. If you have latent (inactive) TB, your doctor should begin TB treatment before you start REMICADE. REMICADE can lower your ability to fight infections, so if you are prone to or have a history of infections, or develop any signs of an infection such as fever, fatigue, cough, flu or warm, red or painful skin while taking REMICADE, tell your doctor right away. Also, tell your doctor if you are scheduled to receive a vaccine or if you have lived in a region where histoplasmosis or coccidioidomycosis is common.

Reports of a type of blood cancer called lymphoma in patients on REMICADE or other TNF blockers are rare but occur more often than expected for people in general. People who have been treated for rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, or psoriatic arthritis for a long time, particularly those with highly active disease may be more prone to develop lymphoma. Cancers, other than lymphoma, have also been reported. Rarely, children and young adults who have been treated for Crohn’s disease with REMICADE in combination with azathioprine or 6-mercaptopurine have developed a rare type of lymphoma, hepatosplenic T cell lymphoma (HSTL), that often results in death. If you take REMICADE or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should also tell your doctor if you have had or develop lymphoma or other cancers or if you have a lung disease called chronic obstructive pulmonary disease (COPD).

Many people with heart failure should not take REMICADE; so prior to treatment you should discuss any heart condition with your doctor. Tell your doctor right away if you develop new or worsening symptoms of heart failure (such as shortness of breath, swelling of your ankles or feet, or sudden weight gain).

Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF blockers, such as REMICADE. Some of these cases have been fatal. Tell your doctor if you know or think you may be a carrier of hepatitis B virus or if you experience signs of hepatitis B infection, such as feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain.

There have been rare cases of serious liver injury in people taking REMICADE, some fatal. Tell your doctor if you have liver problems and contact your doctor immediately if you develop symptoms such as jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe fatigue.

Blood disorders have been reported, some fatal. Tell your doctor if you develop possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking REMICADE. Nervous system disorders have also been reported. Tell your doctor if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, visual disturbances or seizures while taking REMICADE.

Allergic reactions, some severe have been reported during or after infusions with REMICADE. Signs of an allergic reaction include hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills. Tell your doctor if you have experienced a severe allergic reaction. The most common side effects of REMICADE are: respiratory infections, such as sinus infections and sore throat, headache, rash, coughing, and stomach pain.

Please read important information about REMICADE, including full U.S. prescribing information and Medication Guide, at remicade/. For complete EU prescribing information, please visit

About Centocor

Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients’ lives. Centocor has already brought innovation to the treatment of Crohn’s disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn’s disease and psoriasis.

The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders.

CENTOCOR DISCLOSURE NOTICE: This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the Centocor expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at sec/, jnj/ or on request from Johnson & Johnson. Centocor does not undertake to update any forward-looking statements as a result of new information or future events or developments.

About Schering-Plough

Schering-Plough is a global science-based healthcare company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough’s vision is to earn the trust of the physicians, patients and customers served by its approximately 33,500 people around the world. The company is based in Kenilworth, N.J., and its Web site isschering-plough/.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release contains certain “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the international market potential for REMICADE. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough’s forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough’s Securities and Exchange Commission filings, including Part II, Item 1A, “Risk Factors” in Schering-Plough’s third quarter 2007 10-Q.

About Mitsubishi Tanabe Pharma Corporation

Mitsubishi Tanabe Pharma Corporation, one of the leading Japanese pharmaceutical companies, specializes in developing and marketing globally competitive pharmaceutical products in the fields of cardiovascular and metabolic diseases, brain and nerve diseases, and renal and urinary system diseases. The company, established through the merger of Tanabe Seiyaku Co., Ltd. and Mitsubishi Pharma Corporation in October 2007, drives for the expansion of its operations and the reinforcement of its future growth with the aim of becoming a global research-driven pharmaceutical company and taking on challenge of new business opportunities. Mitstubishi Tanabe Pharma Corporation is committed to protect the health of people around the world and contribute to comfortable lifestyles through creating pharmaceuticals. For more information, please visit the web site at


Melissa Katz

Centocor, Inc.

Catherine Cantone
Schering Plough Corporation

View drug information on Remicade.

Bush To Announce $674M in Additional Humanitarian Relief Aid for Africa as Tony Blair Visits White House

President Bush on Tuesday is expected to announce an additional $674 million in aid for African humanitarian relief efforts at a joint news conference with British Prime Minister Tony Blair, according to an unnamed official at the… National Security Council, the New York Times reports (Stevenson, New York Times, 6/7). The money will be directed toward famine relief in Ethiopia, Eritrea and other African countries and will provide food for approximately 14 million people, according to the official. The $674 million will come from a USDA food reserve program and from funding provided by a recent supplemental appropriations bill to support ongoing military operations in Iraq and Afghanistan, the official said. The United States already has pledged $1.4 billion in aid in the current fiscal year through the United Nations and nongovernmental organizations, according to the official (Baker, Washington Post, 6/7). Blair also is expected to announce a British contribution to the initiative, although the amount has not been disclosed (Gardiner, AP/ABCNews, 6/7). The initiative appears to be an effort to “take some of the sting” out of the United States’ “differences” with Britain over African aid, according to the Times (New York Times, 6/7). U.K. Chancellor of the Exchequer Gordon Brown at a February meeting of the Group of Seven industrialized nations proposed increasing aid to developing nations to $100 billion annually through an International Finance Facility, which would frontload development aid to help Africa meet the U.N. Millennium Development Goals. Brown has said that more than 50 countries have expressed support for the initiative, although the United States so far has failed to fully endorse the plan. Although the Bush administration supports 100% debt cancellation for the world’s poorest countries, the United States does not support the U.K. plan to raise funds for poverty alleviation (Kaiser Daily HIV/AIDS Report, 6/2).

“Reprinted with permission from kaisernetwork kaisernetwork. You can view the entire Kaiser Daily HIV/AIDS Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/hiv.. The Kaiser Daily HIV/AIDS Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Old Muscle Given New Pep By Stem Cell Researchers

Old muscle got a shot of youthful vigor in a stem cell experiment by bioengineers at the University of California, Berkeley, setting the path for research on new treatments for age-related degenerative conditions such as muscle atrophy or Alzheimer’s and Parkinson’s diseases.

In a new study published in an advanced online issue of the journal Nature, researchers identified two key regulatory pathways that control how well adult stem cells repair and replace damaged tissue. They then tweaked how those stem cells reacted to those biochemical signals to revive the ability of muscle tissue in old mice to repair itself nearly as well as the muscle in the mice’s much younger counterparts.

Irina Conboy, an assistant professor of bioengineering and an investigator at the Berkeley Stem Cell Center and at the California Institute for Quantitative Biosciences (QB3), led the research team conducting this study.

Because the findings relate to adult stem cells that reside in existing tissue, this approach to rejuvenating degenerating muscle eliminates the ethical and medical complications associated with transplanting tissues grown from embryonic stem cells.

“We are one step closer to having a point of intervention where we can rejuvenate the body’s own stem cells so we don’t have to suffer from some of the debilitating diseases associated with aging,” said the study’s lead author, Morgan Carlson, a recent Ph.D. graduate of Conboy’s lab.

The researchers focused on the interplay of two competing molecular pathways that control the stem cells, which sit next to the mature, differentiated cells that make up our working body parts. When the mature cells are damaged or wear out, the stem cells are called into action to begin the process of rebuilding.

“We don’t realize it, but as we grow our bodies are constantly being remodeled,” said Conboy. “We are constantly falling apart, but we don’t notice it much when we’re young because we’re always being restored. As we age, our stem cells are prevented, through chemical signals, from doing their jobs.”

The good news, the researchers said, is that the stem cells in old tissue are still ready and able to perform their regenerative function if they receive the appropriate chemical signals. Studies have shown that when old tissue is placed in an environment of young blood, the stem cells behave as if they are young again.

“Conversely, we have found in a study published last year that even young stem cells rapidly age when placed among blood and tissue from old mice,” said Carlson, who will stay on at UC Berkeley to expand his work on stem cell engineering either as a QB3 fellow or a postdoctoral researcher. He will be supervised by Conboy; Tom Alber, professor of biochemistry; and David Schaffer, associate director of the Berkeley Stem Cell Center and professor of chemical engineering.

Adult stem cells have a receptor called Notch that, when activated, tells them that it is time to grow and divide, the researchers said. But stem cells also have a receptor for the protein TGF-beta that sets off a chain reaction activating the molecule pSmad3 and ultimately producing cyclin-dependent kinase (CDK) inhibitors, which regulate the cell’s ability to divide.

“Interestingly, activated Notch competes with activated pSmad3 for binding to the regulatory regions of the same CDK inhibitors in the stem cell,” said Conboy. “We found that Notch is capable of physically kicking off pSmad3 from the promoters for the CDK inhibitors within the stem cell’s nucleus, which tells us that a precise manipulation of the balance of these pathways would allow the ability to control stem cell responses.”

Notch and TGF-beta are well known in molecular biology, but Conboy’s lab is the first to connect them to the process of aging, and the first to show that they act in opposition to each other within the nucleus of the adult stem cell.

Aging and the inevitable march towards death are, in part, due to the progressive decline of Notch and the increased levels of TGF-beta , producing a one-two punch to the stem cell’s capacity to effectively rebuild the body, the researchers said.

“What we discovered is the interplay between two pathways – one an aging pathway, and the other a youthful pathway,” said Conboy.

But what would happen if researchers blocked the adult stem cells in old tissues from reacting to those TGF-beta signals? The researchers put that question to the test in a living organism by comparing the muscle regeneration capacity of old, 2-year-old mice, comparable in age to a 75- to 80-year-old human, with that of 2-month-old mice, similar in age to a 20- to 25-year-old human.

For a group of the old mice, the researchers disabled the “aging pathway” that tells stem cells to stop dividing by using an established method of RNA interference that reduced levels of pSmad3. The researchers then examined the muscle of the different groups of mice one to five days after injury to compare how well the tissue repaired itself.

As expected, the researchers found that muscle tissue in the young mice easily replaced damaged cells with new, healthy cells. In contrast, the areas of damaged muscle in the control group of old mice were characterized by fibroblasts and scar tissue.

However, muscles in the old mice whose stem cell “aging pathway” had been dampened showed levels of cellular regeneration that were comparable to their much younger peers, and that were 3 to 4 times greater than those of the group of “untreated” old mice.

The researchers cautioned that shutting down the TGF-beta/pSmad3 pathway altogether by turning off the gene that controls it could lead to many health problems. The ability to suppress cell division is critical in controlling the development of tumors, for instance.

“When we are young, there is an optimal balance between Notch and TGF-beta,” said Conboy. “We need to find out what the levels of these chemicals are in the young so we can calibrate the system when we’re older. If we can do that, we could rejuvenate tissue repair for a very long time.”

The researchers also warn against interpreting this research as the cure-all for aging.

“We’re not at a point where we’re ready to inject ourselves with TGF-beta antibodies and call it a day,” said Carlson. “There are multiple mechanisms involved in how our body functions. We know that TGF-beta is involved in one aspect of aging, but we don’t know where it fits in the global scheme of aging.”

In addition to their work on adult stem cells, Carlson and Conboy have also discovered that human embryonic stem cells can actually neutralize the effects of aging. Conboy received funding last year from the California Institute for Regenerative Medicine (CIRM) to pursue this line of research.

Michael Hsu, a former UC Berkeley postdoctoral researcher in bioengineering, also co-authored this paper.

This study was primarily supported by the National Institutes of Health and The Ellison Medical Foundation, with additional funds from a pre-doctoral training grant from CIRM.

Source: Sarah Yang

University of California – Berkeley

Joint Distraction Promotes Structural Repair In Patients With Severe Knee Osteoarthritis

Joint distraction (the use of a surgical frame around a degenerated joint to strengthen and promote repair) promotes cartilage repair in severe end stage osteoarthritis (OA) of the knee, as demonstrated for the first time by data presented at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France.

In the study, an external fixation frame, with springs, was used to bridge the knee joint in 19 relatively young osteoarthritis patients (

Osteoarthritis of the knee is twice as common in women as in men, mainly occurring in women over the age of 50. So far, no treatment has been available and end stage placement of a joint prosthesis is often inevitable. Delaying such joint replacement surgery and preserving the original joint, specifically in the light of the ageing population, offers significant social and economical potential.

Abstract number: OP0151

The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.

Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 – 5 % of the adult population and are predicted to rise as people live longer.

As new treatments emerge and cellular mechanisms are discovered, EULAR 2008 brings together more than 12,000 experts – scientists, clinicians, healthcare workers, pharmaceutical companies and patients – to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.

To find out more information about the activities of EULAR, visit: eular/

Source: Rory Berrie

European League Against Rheumatism

Institute Of Human Virology Nigeria Program Receives $43M PEPFAR Grant

The Institute of Human Virology at the University of Maryland’s School of Medicine has received a $43 million grant from the President’s Emergency Plan for AIDS Relief to expand HIV/AIDS treatment and care services in Nigeria, the AP/Washington Examiner reports. The grant will go to the institute’s AIDS Care and Treatment in Nigeria, or ACTION, program, which was formed in 2003. ACTION links members of the institute’s medical team with Nigerian counterparts to involve communities in HIV/AIDS treatment and care. The money will be used to provide 48,000 people in Nigeria with treatment and expand HIV testing and counseling to an additional 100,000 people, according to an institute release. ACTION has provided thousands of people in Nigeria with treatment and thousands of pregnant women with HIV prevention services, according to the AP/Examiner. “The work being done now in Nigeria is extraordinary,” Robert Gallo, founder and director of the institute, said, adding, “This new award enables us to reach even more people who need the care and treatment provided by our institute’s experts” (AP/Washington Examiner, 7/9).

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Low Vitamin D Levels Associated With More Asthma Symptoms, Medication Use

Low levels of vitamin D are associated with lower lung function and greater medication use in children with asthma, according to researchers at National Jewish Health. In a paper published online in the Journal of Allergy & Clinical Immunology, Daniel Searing, MD, and his colleagues also reported that vitamin D enhances the activity of corticosteroids, the most effective controller medication for asthma.

“Asthmatic children in our study who had low levels of vitamin D were more allergic, had poorer lung function and used more medications,” said Dr. Searing. “Conversely, our findings suggest that vitamin D supplementation may help reverse steroid resistance in asthmatic children and reduce the effective dose of steroids needed for our patients.”

The researchers examined electronic medical records of 100 pediatric asthma patients referred to National Jewish Health. Overall, 47 percent of them had vitamin D levels considered insufficient, below 30 nanograms per milliliter of blood (ng/mL). Seventeen percent of the patients had levels below 20 ng/mL, which is considered deficient. These levels were similar to vitamin D levels found in the general population.

Patients low in vitamin D generally had higher levels of IgE, a marker of allergy, and responded positively to more allergens in a skin prick test. Allergies to the specific indoor allergens, dog and house dust mite, were higher in patients with low vitamin D levels. Low vitamin D also correlated with low FEV1, the amount of air a person can exhale in one second, and lower FEV1/FVC, another measure of lung function. Use of inhaled steroids, oral steroids and long-acting beta agonists were all higher in patients low in vitamin D.

“Our findings suggest two possible explanations,” said senior author Donald Leung, MD, PhD. “It could be that lower vitamin D levels contribute to increasing asthma severity, which requires more corticosteroid therapy. Or, it may be that vitamin D directly affects steroid activity, and that low levels of vitamin D make the steroids less effective, thus requiring more medication for the same effect.”

The researchers performed a series of laboratory experiments that indicated vitamin D enhances the action of corticosteroids. They cultured some immune cells with the corticosteroid dexamethasone alone and others with vitamin D first, then dexamethasone. The vitamin D significantly increased the effectiveness of dexamethasone. In one experiment vitamin D and dexamethasone together were more effective than 10 times as much dexamethasone alone.

The researchers also incubated immune-system cells for 72 hours with a staphylococcal toxin to induce corticosteroid resistance. Vitamin D restored the activity of dexamethasone.

“Our work suggests that vitamin D enhances the anti-inflammatory function of corticosteroids,’ said Dr. Leung. “If future studies confirm these findings vitamin D may help asthma patients achieve better control of their respiratory symptoms with less medication.”

This study comes on the heels of another paper by National Jewish Health faculty, which showed that low levels of vitamin D in adult asthma patients are associated with lower lung function and reduced responsiveness to corticosteroids.

National Jewish Medical and Research Center