Trubion Pharmaceuticals, Inc., today announced it has initiated a Phase IIb clinical trial of TRU-015, the Company's lead Small Modular ImmunoPharmaceutical (SMIP(TM)) drug candidate for the treatment of rheumatoid arthritis (RA). The randomized,
double-blind, placebo-controlled clinical trial is designed to evaluate
clinical response rates in patients with rheumatoid arthritis. Upon
initiation of this Phase IIb study and pursuant to the terms of its
strategic collaboration with Wyeth (NYSE: WYE), Trubion will receive an
aggregate of $8 million as a milestone payment and reimbursement of prior
manufacturing-related costs.
"We believe our novel SMIP drug candidates represent an advancement in
the treatment of RA," said Peter Thompson, M.D., co-founder, president and
CEO of Trubion. "Our clinical trials so far have demonstrated that TRU-015
measurably improves the signs and symptoms of rheumatoid arthritis and we
look forward to the results of our continuing clinical evaluation of
TRU-015."
TRU-015 Phase IIb Clinical Trial Protocol
The Phase IIb randomized, double-blind, placebo-controlled clinical
trial will enroll approximately 280 rheumatoid arthritis patients. These
patients will be randomized into five groups to evaluate the safety and
efficacy of an infused dose of TRU-015 compared to placebo for a 24-week
period. Building on the findings of Trubion's Phase IIa clinical trial,
this trial will evaluate the effect of a single infusion of TRU-015 ranging
from 200mg to 1,600 mg per patient.
Similar to the Phase IIa study, this study will evaluate composite
measurements of improvement in disease activity derived from parameters
such as tender and swollen joint counts, patient and physician global
assessments, patient assessment of pain and disability, and laboratory
measures of inflammation as defined by the American College of
Rheumatology.
About TRU-015 and SMIPs
Trubion and Wyeth are developing TRU-015, a SMIP drug candidate, as a
potential new therapy for RA. SMIP(TM) drugs represent a novel class of
immunotherapeutics that Trubion believes possess enhanced drug properties
over monoclonal and recombinant antibodies.
In February 2006, the Company completed enrollment in a Phase IIa study
in RA patients designed to demonstrate proof of concept that TRU-015
measurably improves the signs and symptoms of rheumatoid arthritis. In the
first 24 weeks after receiving intravenous infusions of TRU-015, 72 percent
of the subjects experienced a clinical response that is equal to or greater
than that required to achieve an ACR20 response, 28 percent achieved an
ACR50 response and 12 percent achieved an ACR70 response. In these measures
of clinical response, ACR 50 and ACR70 indicate progressively greater
responses from a baseline measure than ACR20, which is defined as an
improvement of at least 20 percent from baseline in counts of both tender
and swollen joints, as well as in at least three of five other disease
activity parameters.
About Rheumatoid Arthritis
According to Datamonitor, RA is estimated to affect approximately 4.3
million people in the United States, Japan and Europe. In 2005, total
reported worldwide sales of protein therapeutics used for the treatment of
RA were $7.6 billion. Total worldwide sales of protein therapeutics for the
treatment of RA are expected to grow to $10 billion in 2010.
About Trubion
Trubion is a biopharmaceutical company creating a pipeline of product
candidates to treat autoimmune disease and cancer. The Company's product
candidates are novel proteins known as single-chain polypeptides and are
designed using its SMIP(TM) custom drug assembly technology. Trubion's
business model is focused on large, established markets and is designed to
reduce clinical development risks by developing product candidates directed
against validated targets. In less than 24 months, the Company designed,
developed and submitted to the FDA an Investigational New Drug application
for its lead product candidate, TRU-015, which is currently being tested in
a Phase IIb clinical trial for the treatment of rheumatoid arthritis. In
December 2005, the Company entered into a collaboration agreement with
Wyeth for the development and worldwide commercialization of certain
therapeutics, including TRU-015. For additional information visit
trubion.
Forward Looking Statements
This press release contains forward looking statements, including,
without limitation, statements related to payments and reimbursements
Trubion expects to receive; Trubion's future clinical development programs
for TRU-015 and other SMIP drug candidates and the timing thereof; the
therapeutic and commercial potential of TRU-015 and other SMIP drug
candidates; future clinical development plans; the details of the clinical
trials; and the anticipated future size of the RA market. Any statements
contained in this press release that are not statements of historical fact
may be deemed to be forward-looking statements. Words such as "believes,"
"anticipates," "plans," "expects," "will," "intends," "potential,"
"possible" and similar expressions are intended to identify forward-looking
statements. These forward-looking statements are based upon Trubion's
current expectations. Forward-looking statements involve risks and
uncertainties. Trubion's actual results and the timing of events could
differ materially from those anticipated in such forward-looking statements
as a result of these risks and uncertainties, which include, without
limitation, the ability of the company to successfully conduct clinical
trials for TRU-015 and other SMIP candidates; the uncertainty of the FDA
approval process and other regulatory requirements; and the therapeutic and
commercial value of Trubion's drug candidates. Trubion expressly disclaims
any obligation or undertaking to release publicly any updates or revisions
to any forward-looking statements contained herein to reflect any change in
the company's expectations with regard thereto or any change in events,
conditions or circumstances on which any such statements are based.
Trubion Pharmaceuticals, Inc
trubion
пятница, 29 июля 2011 г.
вторник, 26 июля 2011 г.
Tocilizumab Shows Sustained Efficacy In Rheumatoid Arthritis
PHILADELPHIA - Investigators are reporting that tolicizumab is an effective, long-term treatment option in multiple subgroups of rheumatoid arthritis (RA) patients.
These include patients who have an inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR), patients who have an inadequate response to anti-TNF inhibitors (TNF-IR), and patients who have not failed methotrexate.
The new results were announced at the 2009 American College of Rheumatology (ACR) Annual Scientific Meeting.
Joseph S. Smolen, MD, chairman of the rheumatology department at the Medical University of Vienna in Vienna, Austria, and colleagues presented 3.5-year data in 3,986 patients.
Tocilizumab is a humanized monoclonal antibody to the interleukin-6 (IL-6) receptor that inhibits IL-6 binding to its receptor, thus preventing IL-6 mediated proinflammatory activity.
The efficacy and safety of tocilizumab in RA patients for up to one year has been demonstrated in phase 3 trials and for up to 2.5 years has been demonstrated in long-term extension studies.
In the updated analysis, the efficacy of tocilizumab in DMARD-IR patients was evidenced by increased numbers of patients who achieved an American College of rheumatology (ACR) ACR50 and ACR70 up to weeks 72 and 96, respectively, and who achieved maintenance of ACR70 for 24 consecutive weeks, low disease activity score (LDAS), and disease activity score including a 28-joint count (DAS28) remission up to week 72.
Thereafter, proportions increased further or were maintained with continued tocilizumab up to week 180.
In anti-TNF-IR and monotherapy patients, the percentages achieving these endpoints increased or were maintained with continued tocilizumab treatment. At 96 weeks, proportions in the DMARD-IR, anti-TNF-IR, and monotherapy groups with health assessment questionnaire (HAQ)=0 were 15%, 8%, and 23%, respectively; the proportions with ?‰¤1 SJC were 46%, 34%, and 55%, respectively; and the proportions with ?‰¤1 total joint count (TJC) were 37%, 23%, and 35%, respectively.
Overall, the analysis shows that during long-term treatment with tocilizumab, the number of patients responding and the magnitude of patient response increased beyond 24 weeks, Dr. Smolen said.
Jill Stein is a Paris-based freelance medical writer.
Jillstein03(at)qmail
These include patients who have an inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR), patients who have an inadequate response to anti-TNF inhibitors (TNF-IR), and patients who have not failed methotrexate.
The new results were announced at the 2009 American College of Rheumatology (ACR) Annual Scientific Meeting.
Joseph S. Smolen, MD, chairman of the rheumatology department at the Medical University of Vienna in Vienna, Austria, and colleagues presented 3.5-year data in 3,986 patients.
Tocilizumab is a humanized monoclonal antibody to the interleukin-6 (IL-6) receptor that inhibits IL-6 binding to its receptor, thus preventing IL-6 mediated proinflammatory activity.
The efficacy and safety of tocilizumab in RA patients for up to one year has been demonstrated in phase 3 trials and for up to 2.5 years has been demonstrated in long-term extension studies.
In the updated analysis, the efficacy of tocilizumab in DMARD-IR patients was evidenced by increased numbers of patients who achieved an American College of rheumatology (ACR) ACR50 and ACR70 up to weeks 72 and 96, respectively, and who achieved maintenance of ACR70 for 24 consecutive weeks, low disease activity score (LDAS), and disease activity score including a 28-joint count (DAS28) remission up to week 72.
Thereafter, proportions increased further or were maintained with continued tocilizumab up to week 180.
In anti-TNF-IR and monotherapy patients, the percentages achieving these endpoints increased or were maintained with continued tocilizumab treatment. At 96 weeks, proportions in the DMARD-IR, anti-TNF-IR, and monotherapy groups with health assessment questionnaire (HAQ)=0 were 15%, 8%, and 23%, respectively; the proportions with ?‰¤1 SJC were 46%, 34%, and 55%, respectively; and the proportions with ?‰¤1 total joint count (TJC) were 37%, 23%, and 35%, respectively.
Overall, the analysis shows that during long-term treatment with tocilizumab, the number of patients responding and the magnitude of patient response increased beyond 24 weeks, Dr. Smolen said.
Jill Stein is a Paris-based freelance medical writer.
Jillstein03(at)qmail
суббота, 23 июля 2011 г.
Biogen Idec's Baminercept Alfa Shows Promise In Patients With Rheumatoid Arthritis
Biogen Idec presented data on baminercept alfa (BG9924, LT??R-Ig), the first dual-mechanism, lymphotoxin-??; (LT-??;) and LIGHT pathway inhibitor in development for the treatment of autoimmune diseases, including rheumatoid arthritis (RA), during the 2008 European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology at the Le Palais de Congr?©s de Paris. Three abstracts were presented, including one podium presentation highlighting the Phase IIa preliminary safety and efficacy data as well as two poster presentations. The Phase IIa data suggest baminercept alfa is well tolerated. DAS, EULAR and other efficacy measures were improved in patients receiving baminercept alfa vs. patients receiving placebo and persisted up to eight weeks after the final baminercept alfa injection.
Podium presentation
* "Preliminary safety and efficacy of Baminercept alfa (BG9924, LT??R-Ig) in the treatment of rheumatoid arthritis" - (Presentation OP-0122 )
Poster presentations
* "Long-term safety assessment of Baminercept alfa (BG9924, LT??R-Ig) in Cynomolgus monkeys - (Poster FRI0156)
* "Treatment of cynomolgus monkeys with Baminercept alfa (BG9924, LT??R-Ig) results in modulation of a specialized vasculature implicated in lymphocyte trafficking to areas of chronic inflammation" = (Poster SAT0040 )
"We are excited to take part in the Annual European Congress of Rheumatology and to share promising results for baminercept alfa," said Ajay Nirula, Director of Medical Research at Biogen Idec. "We are committed to developing new treatment options for those living with RA and are encouraged that results from the Phase IIa study suggest that innovative targeting of a new pathway may be effective in treating this disease."
Phase IIa Data Results
The Phase IIa blinded, multicenter, placebo-controlled trial was designed to assess the safety, pharmacokinetics, pharmacodynamics and efficacy of baminercept with methotrexate, a standard RA therapy, at different dose ranges. Patients (n=47) were randomized in a dose-escalating fashion to receive placebo or one of six doses of baminercept, ranging from 0.01 mg/kg to 3.0 mg/kg once weekly for four weeks, followed by eight weeks of observation. Patients had to have received methotrexate for at least three months prior to enrollment and continued to receive a stable dose of methotrexate throughout the study period.
Study results suggested improvement in the majority of ACR core set measurements (a series of standard measurement criteria for RA symptom and disease improvement) in patients given baminercept compared with placebo. At day 35, patients given baminercept showed an average 60 percent improvement from baseline in swollen joint count and 47 percent improvement in tender joint count, compared with 4.6 percent and 6.7 percent with placebo, respectively. Improvements in these ACR measures persisted for eight weeks after the final baminercept dose. Similar levels of improvements were observed at day 35 in several other standard markers of inflammation and disease progression. ACR scores and other measures improved in a dose dependent manner, with the greatest improvements reported in the groups receiving 1.0 mg/kg and 3.0 mg/kg.
The most common adverse event in patients receiving baminercept was headache. Transient mild-to-moderate flu-like symptoms were observed in 9 patients (25 percent) within 24 hours after the first dose of baminercept. However, these symptoms responded well to paracetamol (acetaminophen) and tended not to recur with subsequent doses. No serious, drug-related adverse events were reported in this study.
Based on the results of the Phase IIa study, Biogen Idec has initiated two Phase IIb trials to study baminercept alfa in combination with methotrexate in patients with moderate to severe RA. 1.) the REACT study for patients with an inadequate response to treatment with DMARD therapy (disease-modifying antirheumatic drug), which completed enrollment earlier this year, and 2.) the RESPOND study for patients having an inadequate response to a TNF inhibitor (biologic therapies that target the TNF pathway). A decision to enter into Phase III development will be made sometime towards the end of 2008 pending analysis of the results of Phase IIb studies.
Rheumatoid Arthritis and the LT-B Pathway
In patients with RA, certain immune cells malfunction and attack the joints, causing painful and chronic inflammation as well as destruction of cartilage, tendons and bones. As in other autoimmune diseases, the immune system mistakes healthy cells for foreign invaders. Though the exact cause of RA is unknown, new research is uncovering the immunologic and genetic factors that play important roles in triggering and perpetuating inflammation of the joints.
As shown in preclinical studies, baminercept alfa is thought to inhibit the function of LT-B and LIGHT, two critical components of the LT-B pathway implicated in the progression of RA and other autoimmune diseases. These molecules are novel members of the TNF superfamily, distinct from TNF-B and lymphotoxin-B targeted by some biologics indicated for RA. Autoimmune diseases are in part characterized by the inappropriate emergence of organized immune cell collections, or lymphoid structures, at sites of inflammation or in immune system tissues. Baminercept alfa is thought to act by inhibiting the formation and maintenance of lymphoid structures and the consequent activation of aberrant immune effector cells implicated in the pathogenesis of autoimmune diseases such as RA. By blocking inappropriate signals from cell-surface LT-B and LIGHT ligands, baminercept alfa may help restore a normal immune environment.
The LT-B pathway was discovered at Biogen Idec, and baminercept alfa is a wholly-owned Biogen Idec molecule that was discovered in collaboration with academic scientists. Baminercept alfa is one of several programs in the company's research and development efforts in rheumatology.
About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling and additional information about the company, please visit biogenidec.
Safe Harbor
This media alert contains "forward-looking statements" regarding Biogen Idec's development of baminercept alfa that are based on current expectations and assumptions that are subject to risks and uncertainties. Only a small number of research and development programs result in commercialization of a product. Factors which could cause actual results to differ materially from Biogen Idec's current expectations include the risk that results observed in the Phase IIa trial may not be predictive of the results to be obtained in the additional studies that would be necessary to demonstrate baminercept alfa to have a positive benefit-risk profile in the treatment of patients with RA. In addition, the company may not be able to meet applicable regulatory standards or regulatory authorities may fail to approve baminercept alfa; and the company may encounter other unexpected hurdles. For further information regarding factors, risks and uncertainties relating to Biogen Idec's drug research and development and other activities, please refer to the filings Biogen Idec has made with the Securities and Exchange Commission, including the "Risk Factors" section of Biogen Idec's Quarterly and Annual Reports, copies of which may be obtained at biogenidec. Biogen Idec assumes no obligation to update and specifically disclaims any duty to update the information in this press release for any reason, except as required by law, even as new information becomes available or other events occur in the future. All forward-looking statements in this press release are qualified in their entirety by this cautionary statement.
Source: Rachi Govil
biogenidec
Podium presentation
* "Preliminary safety and efficacy of Baminercept alfa (BG9924, LT??R-Ig) in the treatment of rheumatoid arthritis" - (Presentation OP-0122 )
Poster presentations
* "Long-term safety assessment of Baminercept alfa (BG9924, LT??R-Ig) in Cynomolgus monkeys - (Poster FRI0156)
* "Treatment of cynomolgus monkeys with Baminercept alfa (BG9924, LT??R-Ig) results in modulation of a specialized vasculature implicated in lymphocyte trafficking to areas of chronic inflammation" = (Poster SAT0040 )
"We are excited to take part in the Annual European Congress of Rheumatology and to share promising results for baminercept alfa," said Ajay Nirula, Director of Medical Research at Biogen Idec. "We are committed to developing new treatment options for those living with RA and are encouraged that results from the Phase IIa study suggest that innovative targeting of a new pathway may be effective in treating this disease."
Phase IIa Data Results
The Phase IIa blinded, multicenter, placebo-controlled trial was designed to assess the safety, pharmacokinetics, pharmacodynamics and efficacy of baminercept with methotrexate, a standard RA therapy, at different dose ranges. Patients (n=47) were randomized in a dose-escalating fashion to receive placebo or one of six doses of baminercept, ranging from 0.01 mg/kg to 3.0 mg/kg once weekly for four weeks, followed by eight weeks of observation. Patients had to have received methotrexate for at least three months prior to enrollment and continued to receive a stable dose of methotrexate throughout the study period.
Study results suggested improvement in the majority of ACR core set measurements (a series of standard measurement criteria for RA symptom and disease improvement) in patients given baminercept compared with placebo. At day 35, patients given baminercept showed an average 60 percent improvement from baseline in swollen joint count and 47 percent improvement in tender joint count, compared with 4.6 percent and 6.7 percent with placebo, respectively. Improvements in these ACR measures persisted for eight weeks after the final baminercept dose. Similar levels of improvements were observed at day 35 in several other standard markers of inflammation and disease progression. ACR scores and other measures improved in a dose dependent manner, with the greatest improvements reported in the groups receiving 1.0 mg/kg and 3.0 mg/kg.
The most common adverse event in patients receiving baminercept was headache. Transient mild-to-moderate flu-like symptoms were observed in 9 patients (25 percent) within 24 hours after the first dose of baminercept. However, these symptoms responded well to paracetamol (acetaminophen) and tended not to recur with subsequent doses. No serious, drug-related adverse events were reported in this study.
Based on the results of the Phase IIa study, Biogen Idec has initiated two Phase IIb trials to study baminercept alfa in combination with methotrexate in patients with moderate to severe RA. 1.) the REACT study for patients with an inadequate response to treatment with DMARD therapy (disease-modifying antirheumatic drug), which completed enrollment earlier this year, and 2.) the RESPOND study for patients having an inadequate response to a TNF inhibitor (biologic therapies that target the TNF pathway). A decision to enter into Phase III development will be made sometime towards the end of 2008 pending analysis of the results of Phase IIb studies.
Rheumatoid Arthritis and the LT-B Pathway
In patients with RA, certain immune cells malfunction and attack the joints, causing painful and chronic inflammation as well as destruction of cartilage, tendons and bones. As in other autoimmune diseases, the immune system mistakes healthy cells for foreign invaders. Though the exact cause of RA is unknown, new research is uncovering the immunologic and genetic factors that play important roles in triggering and perpetuating inflammation of the joints.
As shown in preclinical studies, baminercept alfa is thought to inhibit the function of LT-B and LIGHT, two critical components of the LT-B pathway implicated in the progression of RA and other autoimmune diseases. These molecules are novel members of the TNF superfamily, distinct from TNF-B and lymphotoxin-B targeted by some biologics indicated for RA. Autoimmune diseases are in part characterized by the inappropriate emergence of organized immune cell collections, or lymphoid structures, at sites of inflammation or in immune system tissues. Baminercept alfa is thought to act by inhibiting the formation and maintenance of lymphoid structures and the consequent activation of aberrant immune effector cells implicated in the pathogenesis of autoimmune diseases such as RA. By blocking inappropriate signals from cell-surface LT-B and LIGHT ligands, baminercept alfa may help restore a normal immune environment.
The LT-B pathway was discovered at Biogen Idec, and baminercept alfa is a wholly-owned Biogen Idec molecule that was discovered in collaboration with academic scientists. Baminercept alfa is one of several programs in the company's research and development efforts in rheumatology.
About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling and additional information about the company, please visit biogenidec.
Safe Harbor
This media alert contains "forward-looking statements" regarding Biogen Idec's development of baminercept alfa that are based on current expectations and assumptions that are subject to risks and uncertainties. Only a small number of research and development programs result in commercialization of a product. Factors which could cause actual results to differ materially from Biogen Idec's current expectations include the risk that results observed in the Phase IIa trial may not be predictive of the results to be obtained in the additional studies that would be necessary to demonstrate baminercept alfa to have a positive benefit-risk profile in the treatment of patients with RA. In addition, the company may not be able to meet applicable regulatory standards or regulatory authorities may fail to approve baminercept alfa; and the company may encounter other unexpected hurdles. For further information regarding factors, risks and uncertainties relating to Biogen Idec's drug research and development and other activities, please refer to the filings Biogen Idec has made with the Securities and Exchange Commission, including the "Risk Factors" section of Biogen Idec's Quarterly and Annual Reports, copies of which may be obtained at biogenidec. Biogen Idec assumes no obligation to update and specifically disclaims any duty to update the information in this press release for any reason, except as required by law, even as new information becomes available or other events occur in the future. All forward-looking statements in this press release are qualified in their entirety by this cautionary statement.
Source: Rachi Govil
biogenidec
среда, 20 июля 2011 г.
Celebrex Approved To Treat Juvenile Rheumatoid Arthritis
The U.S. Food and Drug Administration (FDA) today approved Celebrex (celecoxib) for a new use - the relief of the signs and symptoms of Juvenile Rheumatoid Arthritis (JRA) in patients two years of age and older. Today's approval follows the November 29 meeting of FDA's Arthritis Advisory Committee, in which the committee voted 15 to 1 in favor of approval of this product.
JRA is an autoimmune disease that affects approximately 30,000 to 60,000 children in the United States. The disease is associated with joint swelling, pain, decreased range of motion and abnormalities of growth and development. In some cases, systemic complications may occur including uveitis, a chronic inflammation of the eye. In severe, uncontrolled cases, permanent disability may occur due to progressive joint damage.
???JRA is often a devastating disease,??? said Dr. Steven Galson, Director of FDA??™s Center for Drug Evaluation and Research. ???While there are other medicines approved for the treatment of this disorder, for some children they may have limited effectiveness or cause intolerable side effects. Celebrex will be a needed additional treatment option for children.???
A 24-week study of Celebrex involving 242 patients between the ages of two and 17 years demonstrated its effectiveness in treating JRA. The most commonly reported side effects were cough, cold, upper respiratory tract infection, abdominal pain, headache, fever, nausea, diarrhea and vomiting.
Celebrex has not been studied in patients under the age of two years, in patients who weigh less than 22 pounds, or in patients showing signs of having ???systemic onset JRA???, a more serious type of JRA associated with high fever and rash. Celebrex should be used only with caution in patients with systemic onset JRA due to the risk for serious adverse reactions, including abnormal clotting tests, which can be associated with the clinical condition known as disseminated intravascular coagulation (DIC). DIC is a serious condition in which the body's blood clotting mechanisms are activated throughout the body instead of being localized to an area of injury.
Safety and efficacy were not studied beyond six months, and experience with adults suggests the possibility of longer term cardiovascular problems. As part of the approval of Celebrex, the drug's manufacturer has agreed to conduct two Phase 4 postmarketing studies: a short-term controlled trial to evaluate high blood pressure, and a several-year registry study to further evaluate long-term safety issues, including renal toxicity, high blood pressure, and cardiovascular events.
Celebrex, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID), was originally approved in l998 for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis in adults. Celebrex is manufactured by Pfizer Inc. of New York, NY.
For more information on Celebrex and COX-2 drugs, click here
JRA is an autoimmune disease that affects approximately 30,000 to 60,000 children in the United States. The disease is associated with joint swelling, pain, decreased range of motion and abnormalities of growth and development. In some cases, systemic complications may occur including uveitis, a chronic inflammation of the eye. In severe, uncontrolled cases, permanent disability may occur due to progressive joint damage.
???JRA is often a devastating disease,??? said Dr. Steven Galson, Director of FDA??™s Center for Drug Evaluation and Research. ???While there are other medicines approved for the treatment of this disorder, for some children they may have limited effectiveness or cause intolerable side effects. Celebrex will be a needed additional treatment option for children.???
A 24-week study of Celebrex involving 242 patients between the ages of two and 17 years demonstrated its effectiveness in treating JRA. The most commonly reported side effects were cough, cold, upper respiratory tract infection, abdominal pain, headache, fever, nausea, diarrhea and vomiting.
Celebrex has not been studied in patients under the age of two years, in patients who weigh less than 22 pounds, or in patients showing signs of having ???systemic onset JRA???, a more serious type of JRA associated with high fever and rash. Celebrex should be used only with caution in patients with systemic onset JRA due to the risk for serious adverse reactions, including abnormal clotting tests, which can be associated with the clinical condition known as disseminated intravascular coagulation (DIC). DIC is a serious condition in which the body's blood clotting mechanisms are activated throughout the body instead of being localized to an area of injury.
Safety and efficacy were not studied beyond six months, and experience with adults suggests the possibility of longer term cardiovascular problems. As part of the approval of Celebrex, the drug's manufacturer has agreed to conduct two Phase 4 postmarketing studies: a short-term controlled trial to evaluate high blood pressure, and a several-year registry study to further evaluate long-term safety issues, including renal toxicity, high blood pressure, and cardiovascular events.
Celebrex, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID), was originally approved in l998 for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis in adults. Celebrex is manufactured by Pfizer Inc. of New York, NY.
For more information on Celebrex and COX-2 drugs, click here
воскресенье, 17 июля 2011 г.
FDA: Cancer Warnings Required For TNF Blockers
The U.S. Food and Drug Administration is requiring stronger warnings in the prescribing information for a class of drugs known as TNF blockers. The warnings, which include an updated boxed warning, highlight the increased risk of cancer in children and adolescents who receive these drugs to treat juvenile rheumatoid arthritis, the inflammatory bowel disorder, Crohn's disease, and other inflammatory diseases.
In addition, the FDA is working with manufacturers to explore new ways to further define the risk of cancer in children and adolescents who use these drugs.
TNF blockers target and neutralize tumor necrosis factor-alpha (TNF-?±), a protein that, when overproduced in the body due to chronic inflammatory diseases, can cause inflammation and damage to bones, cartilage and tissue. The drugs in this class include Remicade (infliximab), Enbrel (etancercept), Humira (adalimumab), Cimzia (certolizumab pegol) and Simponi (golimumab).
Today's action is based on the completion of an investigation first announced by the FDA in June 2008. An analysis of U.S. reports of cancer in children and adolescents treated with TNF-blockers showed an increased risk of cancer, occurring after 30 months of treatment on average. About half of the cancers were lymphomas, a type of cancer involving cells of the immune system. Some of the reported cancers were fatal.
Additional required updates to the prescribing information include incorporation of reports of psoriasis associated with the use of TNF blockers.
For more information see:
Update to June 2008 Early Communication about an Ongoing Safety Review of TNF Blockers
Information for Healthcare Professionals
June 2008 Early Communication about an Ongoing Safety Review of TNF Blockers
Source
U.S. Food and Drug Administration
View drug information on Cimzia; Enbrel; Humira.
In addition, the FDA is working with manufacturers to explore new ways to further define the risk of cancer in children and adolescents who use these drugs.
TNF blockers target and neutralize tumor necrosis factor-alpha (TNF-?±), a protein that, when overproduced in the body due to chronic inflammatory diseases, can cause inflammation and damage to bones, cartilage and tissue. The drugs in this class include Remicade (infliximab), Enbrel (etancercept), Humira (adalimumab), Cimzia (certolizumab pegol) and Simponi (golimumab).
Today's action is based on the completion of an investigation first announced by the FDA in June 2008. An analysis of U.S. reports of cancer in children and adolescents treated with TNF-blockers showed an increased risk of cancer, occurring after 30 months of treatment on average. About half of the cancers were lymphomas, a type of cancer involving cells of the immune system. Some of the reported cancers were fatal.
Additional required updates to the prescribing information include incorporation of reports of psoriasis associated with the use of TNF blockers.
For more information see:
Update to June 2008 Early Communication about an Ongoing Safety Review of TNF Blockers
Information for Healthcare Professionals
June 2008 Early Communication about an Ongoing Safety Review of TNF Blockers
Source
U.S. Food and Drug Administration
View drug information on Cimzia; Enbrel; Humira.
четверг, 14 июля 2011 г.
Nuvo Receives Approvable Letter From U.S. FDA For Pennsaid
Nuvo Research Inc.
(TSX:NRI) today announced that it has received an approvable letter from
the U.S. Food and Drug Administration (FDA) for Pennsaid(R) (1.5% w/w
diclofenac sodium solution), a topical non-steroidal anti-inflammatory
(NSAID) developed by Nuvo for use as a treatment of osteoarthritis (OA) of
the knee. Pennsaid is based on Nuvo's skin-penetrating technology that
allows diclofenac to be delivered directly to the knee via topical
application to the surface of the skin thus minimizing systemic side
effects often associated with oral therapies.
In its letter, the FDA indicated that Pennsaid is approvable subject to
Nuvo satisfying certain conditions. The Company plans to meet with the FDA
early in 2007 to discuss the letter.
"This approvable letter is a great achievement for our Company and a
step forward to the commercialization of Pennsaid in the U.S.," said Dr.
Henrich Guntermann, Nuvo's President and CEO. "We plan to work closely with
the FDA to resolve these outstanding matters required to obtain final
approval and expect to provide further information following our meeting
with the FDA."
The Arthritis Foundation estimates that more than 21 million Americans
suffer from osteoarthritis. Pennsaid would be the first topical NSAID
product approved in the United States where the osteoarthritis pain relief
market is estimated at $4 billion US.
Nuvo's amended New Drug Application (NDA) for Pennsaid was re-submitted
to the FDA and accepted for review in July 2006. To meet the FDA's clinical
efficacy and safety requirements as stated in an August 2002 non-approvable
(NA) letter, Nuvo conducted study 112, a 12-week Phase III, 5-arm,
double-blind trial of 775 patients. This trial enrolled patients in the
U.S. and Canada with symptoms of primary osteoarthritis of the knee. The
trial met all of its primary endpoints, being pain, physical function and
patient overall health assessment. The trial also demonstrated comparable
efficacy of Pennsaid to oral diclofenac. In total, more than 2,500 patients
have been exposed to Pennsaid in clinical studies.
To address the long-term safety requirements as stated in the August
2002 NA letter, Nuvo conducted study 112E, a long-term multi-centre,
single-arm safety study of Pennsaid applied by patients with symptoms of
osteoarthritis of the knee. In total, 793 patients were treated, including
448 patients for at least six months and 116 patients for at least one
year. The key observation was that long-term use did not cause any new,
unexpected adverse events.
About Pennsaid
Pennsaid is a topical non-steroidal anti-inflammatory (NSAID) used for
the treatment of osteoarthritis and is currently approved for sale in
Canada and several European countries. Pennsaid allows the diclofenac
solution to be delivered to a specific site via the surface of the skin and
thus avoids complications associated with systemic delivery. According to
published clinical trials, Pennsaid is as effective as the maximum daily
dose of comparable oral medication at relieving pain and stiffness
associated with osteoarthritis of the knee, as well as improving overall
well-being.
About Nuvo Research Inc.
Nuvo is focused on developing innovative site-specific therapeutics
that are delivered topically using the Company's skin-penetrating
technologies. Nuvo's lead product is Pennsaid(R), a topical non-steroidal
anti-inflammatory (NSAID) used for the treatment of osteoarthritis. Nuvo
intends to leverage its skin-penetrating technologies to create a portfolio
of transdermal products targeting a variety of indications.
Nuvo Research Inc. is a publicly traded, Canadian pharmaceutical
company headquartered in Mississauga, Ontario, with its research and
development facility in San Diego, California and manufacturing facilities
in Varennes, Quebec and Wanzleben, Germany. For more information, please
visit nuvoresearch.
This release may contain forward-looking statements, subject to risks
and uncertainties beyond management's control. Actual results could differ
materially from those expressed here. Risk factors are discussed in the
Company's annual information form filed with the securities commissions in
each of the provinces of Canada. The Company undertakes no obligation to
revise forward-looking statements in light of future events.
Nuvo Research Inc.
nuvoresearch
View drug information on Pennsaid.
(TSX:NRI) today announced that it has received an approvable letter from
the U.S. Food and Drug Administration (FDA) for Pennsaid(R) (1.5% w/w
diclofenac sodium solution), a topical non-steroidal anti-inflammatory
(NSAID) developed by Nuvo for use as a treatment of osteoarthritis (OA) of
the knee. Pennsaid is based on Nuvo's skin-penetrating technology that
allows diclofenac to be delivered directly to the knee via topical
application to the surface of the skin thus minimizing systemic side
effects often associated with oral therapies.
In its letter, the FDA indicated that Pennsaid is approvable subject to
Nuvo satisfying certain conditions. The Company plans to meet with the FDA
early in 2007 to discuss the letter.
"This approvable letter is a great achievement for our Company and a
step forward to the commercialization of Pennsaid in the U.S.," said Dr.
Henrich Guntermann, Nuvo's President and CEO. "We plan to work closely with
the FDA to resolve these outstanding matters required to obtain final
approval and expect to provide further information following our meeting
with the FDA."
The Arthritis Foundation estimates that more than 21 million Americans
suffer from osteoarthritis. Pennsaid would be the first topical NSAID
product approved in the United States where the osteoarthritis pain relief
market is estimated at $4 billion US.
Nuvo's amended New Drug Application (NDA) for Pennsaid was re-submitted
to the FDA and accepted for review in July 2006. To meet the FDA's clinical
efficacy and safety requirements as stated in an August 2002 non-approvable
(NA) letter, Nuvo conducted study 112, a 12-week Phase III, 5-arm,
double-blind trial of 775 patients. This trial enrolled patients in the
U.S. and Canada with symptoms of primary osteoarthritis of the knee. The
trial met all of its primary endpoints, being pain, physical function and
patient overall health assessment. The trial also demonstrated comparable
efficacy of Pennsaid to oral diclofenac. In total, more than 2,500 patients
have been exposed to Pennsaid in clinical studies.
To address the long-term safety requirements as stated in the August
2002 NA letter, Nuvo conducted study 112E, a long-term multi-centre,
single-arm safety study of Pennsaid applied by patients with symptoms of
osteoarthritis of the knee. In total, 793 patients were treated, including
448 patients for at least six months and 116 patients for at least one
year. The key observation was that long-term use did not cause any new,
unexpected adverse events.
About Pennsaid
Pennsaid is a topical non-steroidal anti-inflammatory (NSAID) used for
the treatment of osteoarthritis and is currently approved for sale in
Canada and several European countries. Pennsaid allows the diclofenac
solution to be delivered to a specific site via the surface of the skin and
thus avoids complications associated with systemic delivery. According to
published clinical trials, Pennsaid is as effective as the maximum daily
dose of comparable oral medication at relieving pain and stiffness
associated with osteoarthritis of the knee, as well as improving overall
well-being.
About Nuvo Research Inc.
Nuvo is focused on developing innovative site-specific therapeutics
that are delivered topically using the Company's skin-penetrating
technologies. Nuvo's lead product is Pennsaid(R), a topical non-steroidal
anti-inflammatory (NSAID) used for the treatment of osteoarthritis. Nuvo
intends to leverage its skin-penetrating technologies to create a portfolio
of transdermal products targeting a variety of indications.
Nuvo Research Inc. is a publicly traded, Canadian pharmaceutical
company headquartered in Mississauga, Ontario, with its research and
development facility in San Diego, California and manufacturing facilities
in Varennes, Quebec and Wanzleben, Germany. For more information, please
visit nuvoresearch.
This release may contain forward-looking statements, subject to risks
and uncertainties beyond management's control. Actual results could differ
materially from those expressed here. Risk factors are discussed in the
Company's annual information form filed with the securities commissions in
each of the provinces of Canada. The Company undertakes no obligation to
revise forward-looking statements in light of future events.
Nuvo Research Inc.
nuvoresearch
View drug information on Pennsaid.
понедельник, 11 июля 2011 г.
Chlamydia May Play Role In A Type Of Arthritis
Spondylarthritis (SpA) represents a group of arthritidies that share clinical features such as inflammatory back pain and inflammation at sites where tendons attach to bone. It includes ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel-disease-related arthritis, reactive arthritis (ReA) and undifferentiated spondylarthritides (uSpA). Since Chlamydia trachomatis or Chlamydia pneumoniae (which are often asymptomatic) frequently cause ReA, a new study examined whether there was a connection between these two infections and uSpA. The study was published in the May issue of Arthritis & Rheumatism.
Led by John D. Carter of theUniversity of South Florida, the study involved blood and synovial tissue analysis from 26 patients who had chronic uSpA or Chlamydia-induced ReA. Synovial tissue samples from 167 osteoarthritis patients were used as controls. Samples were analyzed to assess chlamydial DNA and the 26 subjects were asked if they had any known exposure to Chlamydia trachomatis or Chlamydia pneumoniae and if so, the infection was documented in relation to the onset of their uSpA. They also underwent a physical exam that included evaluation of swollen and tender joints and other symptoms of SpA. The results showed that the rate of Chlamydia infection was 62 percent in uSpA patients, significantly higher than the 12 percent seen in control subjects.
It is believed that as many as 150,000 cases of Chlamydia trachomatis-induced ReA may appear in the U.S. each year compared to about 125,000 new cases of rheumatoid arthritis. This is a low estimate since it does not include cases resulting from Chlamydia pneumoniae. "Thus, Chlamydia-induced ReA represents a considerable burden on the health care systems of the U.S. and other nations, and its impact on those systems may well be significantly underrecognized," the authors state.
Most women with genital Chlamydia trachomatis infection have no symptoms at the time of the initial infection; this was also true of the patients in the study who had DNA evidence of Chlamydia. For Chlamydia pneumoniae, as many as 70 percent of acute infections are asymptomatic and, even when there are symptoms, definitive identification of the organism is rare. The authors point out that relying on identification of a symptomatic infection may therefore result in routine underdiagnosis or misdiagnosis of Chlamydia-induced ReA.
They add that because ReA is a type of SpA and patients with ReA do not present with the classic combination of symptoms of arthritis, conjunctivitis/iritis and urethritis, it is reasonable to believe that Chlamydia trachomatis plays a role in causing uSpA, which may in fact be ReA. They conclude that although there is no diagnostic test for Chlamydia-induced ReA, testing for chlamydial DNA in the synovial tissue of patients thought to have ReA may be the most accurate way of diagnosing the condition.
Article: "Chlamydiae as Etiologic Agents in Chronic Undifferentiated Spondylarthritis," John D. Carter, Herv?© C. G?©rard, Luis R. Espinoza, Louis R. Ricca, Joanne Valeriano, Jessica Snelgrove, Cynthia Oszust, Frank B. Vasey, Alan P. Hudson, Arthritis & Rheumatism, May 2009.
Source:
Sean Wagner
Wiley-Blackwell
Led by John D. Carter of theUniversity of South Florida, the study involved blood and synovial tissue analysis from 26 patients who had chronic uSpA or Chlamydia-induced ReA. Synovial tissue samples from 167 osteoarthritis patients were used as controls. Samples were analyzed to assess chlamydial DNA and the 26 subjects were asked if they had any known exposure to Chlamydia trachomatis or Chlamydia pneumoniae and if so, the infection was documented in relation to the onset of their uSpA. They also underwent a physical exam that included evaluation of swollen and tender joints and other symptoms of SpA. The results showed that the rate of Chlamydia infection was 62 percent in uSpA patients, significantly higher than the 12 percent seen in control subjects.
It is believed that as many as 150,000 cases of Chlamydia trachomatis-induced ReA may appear in the U.S. each year compared to about 125,000 new cases of rheumatoid arthritis. This is a low estimate since it does not include cases resulting from Chlamydia pneumoniae. "Thus, Chlamydia-induced ReA represents a considerable burden on the health care systems of the U.S. and other nations, and its impact on those systems may well be significantly underrecognized," the authors state.
Most women with genital Chlamydia trachomatis infection have no symptoms at the time of the initial infection; this was also true of the patients in the study who had DNA evidence of Chlamydia. For Chlamydia pneumoniae, as many as 70 percent of acute infections are asymptomatic and, even when there are symptoms, definitive identification of the organism is rare. The authors point out that relying on identification of a symptomatic infection may therefore result in routine underdiagnosis or misdiagnosis of Chlamydia-induced ReA.
They add that because ReA is a type of SpA and patients with ReA do not present with the classic combination of symptoms of arthritis, conjunctivitis/iritis and urethritis, it is reasonable to believe that Chlamydia trachomatis plays a role in causing uSpA, which may in fact be ReA. They conclude that although there is no diagnostic test for Chlamydia-induced ReA, testing for chlamydial DNA in the synovial tissue of patients thought to have ReA may be the most accurate way of diagnosing the condition.
Article: "Chlamydiae as Etiologic Agents in Chronic Undifferentiated Spondylarthritis," John D. Carter, Herv?© C. G?©rard, Luis R. Espinoza, Louis R. Ricca, Joanne Valeriano, Jessica Snelgrove, Cynthia Oszust, Frank B. Vasey, Alan P. Hudson, Arthritis & Rheumatism, May 2009.
Source:
Sean Wagner
Wiley-Blackwell
пятница, 8 июля 2011 г.
Drug Reduces Airway Mucus In Preclinical Asthma Model
Inverseon, Inc.
announces the publication of a
rapid communication of groundbreaking research led by
Professor Richard Bond of the University of Houston,
Inverseon's Scientific Founder. In the March article by
Nguyen, et. al., in the American Journal of Respiratory Cell
and Molecular Biology 2008; 38: 256-262, entitled, "Chronic
Exposure to Beta-Blockers Attenuates Inflammation and Mucin
Content in a Murine Asthma Model," airway mucus
hypersecretion and inflammation were almost completely
reversed upon treatment with certain beta blockers. The
Journal commented that, "This research may result in a
paradigm shift in the treatment of asthma. This research
demonstrates the importance that duration of therapy has on
clinical and physiologic responses."
"It is gratifying to see these findings, which were
originally described in Prof. Bond's laboratory, confirmed
in a respected independent laboratory," commented William J.
Garner, MD, Chairman of Inverseon.
About Inverseon, Inc.
Inverseon's product development programs target significant
unmet medical needs and major market opportunities in
chronic pulmonary diseases such as asthma, COPD and
pulmonary hypertension. Inverseon was founded based on the
original work of Prof. Richard Bond of the University of
Houston. Professor Bond termed the effects "Paradoxical
Pharmacology," based on the divergence of acute versus
chronic effects of certain drugs in chronic diseases. For
further information, please visit Inverseon's website at
inverseon.
Forward-Looking Statement
This press release may contain forward-looking statements.
In some cases, you can identify forward-looking statements
by terminology such as "may," "will," "should," "expect,"
"plan," "anticipate," "believe," "estimate," "predict,"
"potential" or "continue," the negative of such terms, or
other comparable terminology. These statements are only
predictions. Although we believe that the expectations
reflected in the forward-looking statements are reasonable,
such statements should not be regarded as a representation
by the Company, or any other person, that such
forward-looking statements will be achieved. We undertake no
duty to update any of the forward-looking statements,
whether as a result of new information, future events, or
otherwise. In light of the foregoing, readers are cautioned
not to place undue reliance on such forward-looking
statements.
Inverseon, Inc.
announces the publication of a
rapid communication of groundbreaking research led by
Professor Richard Bond of the University of Houston,
Inverseon's Scientific Founder. In the March article by
Nguyen, et. al., in the American Journal of Respiratory Cell
and Molecular Biology 2008; 38: 256-262, entitled, "Chronic
Exposure to Beta-Blockers Attenuates Inflammation and Mucin
Content in a Murine Asthma Model," airway mucus
hypersecretion and inflammation were almost completely
reversed upon treatment with certain beta blockers. The
Journal commented that, "This research may result in a
paradigm shift in the treatment of asthma. This research
demonstrates the importance that duration of therapy has on
clinical and physiologic responses."
"It is gratifying to see these findings, which were
originally described in Prof. Bond's laboratory, confirmed
in a respected independent laboratory," commented William J.
Garner, MD, Chairman of Inverseon.
About Inverseon, Inc.
Inverseon's product development programs target significant
unmet medical needs and major market opportunities in
chronic pulmonary diseases such as asthma, COPD and
pulmonary hypertension. Inverseon was founded based on the
original work of Prof. Richard Bond of the University of
Houston. Professor Bond termed the effects "Paradoxical
Pharmacology," based on the divergence of acute versus
chronic effects of certain drugs in chronic diseases. For
further information, please visit Inverseon's website at
inverseon.
Forward-Looking Statement
This press release may contain forward-looking statements.
In some cases, you can identify forward-looking statements
by terminology such as "may," "will," "should," "expect,"
"plan," "anticipate," "believe," "estimate," "predict,"
"potential" or "continue," the negative of such terms, or
other comparable terminology. These statements are only
predictions. Although we believe that the expectations
reflected in the forward-looking statements are reasonable,
such statements should not be regarded as a representation
by the Company, or any other person, that such
forward-looking statements will be achieved. We undertake no
duty to update any of the forward-looking statements,
whether as a result of new information, future events, or
otherwise. In light of the foregoing, readers are cautioned
not to place undue reliance on such forward-looking
statements.
Inverseon, Inc.
вторник, 5 июля 2011 г.
Biologist's Findings on Fertility and Status in Monkeys Generate Scientific, Media Interest
University of California, Riverside Assistant Adjunct Professor of Biology Wendy Saltzman's inquiries into the role
social position plays in the fertility of female marmosets were the recent subject of a presentation at the American
Association for the Advancement of Science and on the BBC 4 radio show.... "Leading Edge ."
On Monday, Feb. 21, Saltzman presented her findings as part of an eight-member panel titled Comparative Perspectives on Brain
and Behavior at the annual meeting of the American Association for the Advancement of Science in Washington D.C. On March 10,
the BBC aired an interview with Saltzman by Geoff Watts of the BBC 4 radio show "Leading Edge" on the links between dominance
in female marmosets and their fertility. Saltzman's findings show that subordinate females fail to ovulate, becoming
infertile.
Saltzman's research touches on the interactions among hormones, the brain and behavior. In many species, interactions with
social partners can profoundly affect an individual's reproductive functioning. Among primates, the social regulation of
fertility is especially pronounced in the marmosets and tamarins, New World monkeys in which socially subordinate females
often remain infertile and sexually inactive until they become dominant.
Researchers think this hormonally-mediated change benefits the subordinate females, because even though these monkeys will
not be passing along their genes, they will be helping to rear closely related infants.
When subordinate females do breed, their infants are likely to be killed by the dominant female, Saltzman and her colleagues
have recently found. So, by switching off their fertility, subordinate females may avoid investing significant resources in
infants that aren't likely to survive. Fertile marmosets usually have twins twice a year and need a lot of help from their
family group to successfully rear their young.
"What's most exciting is learning how the social environment can profoundly affect an individual's fertility," she said.
"This is an excellent model system for studying this issue."
According to Saltzman, understanding these mechanisms can advance the understanding of the social regulation of fertility in
humans and other animals.
Wendy Saltzman's faculty Web page
Additional Contacts:
The University of California, Riverside is a major research institution and a national center for the humanities. Key areas
of research include nanotechnology, genomics, environmental studies, digital arts and sustainable growth and development.
With a current undergraduate and graduate enrollment of nearly 17,000, the campus is projected to grow to 21,000 students by
2010. Located in the heart of inland Southern California, the nearly 1,200-acre, park-like campus is at the center of the
region's economic development. Visit ucr or call 951-UCR-NEWS
for more information. Media sources are available at mediasources.ucr.
Contact: Ricardo Duran
ricardo.duranucr
951-827-5893
University of California - Riverside
ucr
social position plays in the fertility of female marmosets were the recent subject of a presentation at the American
Association for the Advancement of Science and on the BBC 4 radio show.... "Leading Edge ."
On Monday, Feb. 21, Saltzman presented her findings as part of an eight-member panel titled Comparative Perspectives on Brain
and Behavior at the annual meeting of the American Association for the Advancement of Science in Washington D.C. On March 10,
the BBC aired an interview with Saltzman by Geoff Watts of the BBC 4 radio show "Leading Edge" on the links between dominance
in female marmosets and their fertility. Saltzman's findings show that subordinate females fail to ovulate, becoming
infertile.
Saltzman's research touches on the interactions among hormones, the brain and behavior. In many species, interactions with
social partners can profoundly affect an individual's reproductive functioning. Among primates, the social regulation of
fertility is especially pronounced in the marmosets and tamarins, New World monkeys in which socially subordinate females
often remain infertile and sexually inactive until they become dominant.
Researchers think this hormonally-mediated change benefits the subordinate females, because even though these monkeys will
not be passing along their genes, they will be helping to rear closely related infants.
When subordinate females do breed, their infants are likely to be killed by the dominant female, Saltzman and her colleagues
have recently found. So, by switching off their fertility, subordinate females may avoid investing significant resources in
infants that aren't likely to survive. Fertile marmosets usually have twins twice a year and need a lot of help from their
family group to successfully rear their young.
"What's most exciting is learning how the social environment can profoundly affect an individual's fertility," she said.
"This is an excellent model system for studying this issue."
According to Saltzman, understanding these mechanisms can advance the understanding of the social regulation of fertility in
humans and other animals.
Wendy Saltzman's faculty Web page
Additional Contacts:
The University of California, Riverside is a major research institution and a national center for the humanities. Key areas
of research include nanotechnology, genomics, environmental studies, digital arts and sustainable growth and development.
With a current undergraduate and graduate enrollment of nearly 17,000, the campus is projected to grow to 21,000 students by
2010. Located in the heart of inland Southern California, the nearly 1,200-acre, park-like campus is at the center of the
region's economic development. Visit ucr or call 951-UCR-NEWS
for more information. Media sources are available at mediasources.ucr.
Contact: Ricardo Duran
ricardo.duranucr
951-827-5893
University of California - Riverside
ucr
суббота, 2 июля 2011 г.
Cellular Channel May Open Doors To Skin Conditions, Hair Growth
Skin and hair follicles are constantly renewed in the body, maintained by specialized stem cells. New research from Children's Hospital Boston identifies a small cellular channel that regulates skin and hair growth and that could be targeted with small-molecule drugs, potentially treating variety of skin conditions, as well as thinning hair or unwanted hair growth. Findings appear in the April 16 issue of Cell.
Several known factors regulate the growth and specialization of cells in the epidermis. Two key players are transforming growth factor alpha (TGF-alpha) and the receptor for epidermal growth factor (EGFR). Without them, mice have wavy hair; when they are over-active, mice are hairless and develop skin cancer. However, these growth factors don't make ideal targets for a drug treatment since they are found throughout the body, and any drug targeting them would have substantial side effects.
The new study, led by David Clapham, MD, PhD, of Children's Hospital Boston, and Haoxing Xu, PhD, of the University of Michigan, finds that another protein found mainly in skin, TRPV3, "supercharges" the TGF-alpha/EGFR pathway. When TRPV3 was knocked out, the mice had a thinner outer skin layer with a dry, scaly texture, and appeared to be a less intact, more permeable barrier. By comparison, the normal mice formed a thick, robust outer skin barrier, with more tightly linked, toughened cells (a process known as cornification).
The mice lacking TRPV3 also developed a wavy coat and curly whiskers. Clapham believes the waviness resulted from abnormal functioning of the epidermal cells at the base of the hair follicle, normally rich in TRPV3, causing the follicles to point in different directions and preventing them from smoothly extruding hair.
TRVP3 is an ion channel, a small pore that opens to admit calcium ions into the cell. Experiments showed that it is activated by EGFR, causing an influx of calcium that triggers many signaling pathways inside the cell, including one that stimulates release of TGF-alpha. This, in turn, increases EGFR signaling, providing a positive feedback loop that "supercharges" the system. When TRPV3 was knocked out, TGF-alpha/EGFR signaling was impaired.
Clapham speculates that drugs that stimulate TRPV3 activity may offer a new approach to treating multiple skin conditions, such as burns, bed sores, eczema, psoriasis, itch, fungal infections and oral mucositis (a sloughing off of skin in the mouth due to cancer chemotherapy). It might also be possible to develop cosmetic treatments that make the skin more firm, pliable and youthful. "If you activate TRPV3, you might get thicker skin," he says.
On the flip side, reducing TRPV3 activity could curb uncontrolled cell growth in skin cancer. "Some skin cancers may be potentiated by TRPV3," says Clapham.
A more speculative possibility is that TRPV3 could be targeted to create hair growth or hair removal agents, he adds.
Unlike growth factors, which act in many tissues and can have significant side effects, TRPV3 is found mainly in skin keratinocytes, although it is also found in the brain. Because TRPV3 has also been found to play a role in pain sensation, pharmaceutical companies have already been developing small molecule drugs targeting it.
The study was funded by the Howard Hughes Medical Institute, the National Institutes of Health and the University of Michigan. Xiping Cheng, PhD, of the University of Michigan and Jie Jin, PhD, of Children's Hospital Boston were first authors.
Citation:
Cheng X et al. TRP Channel regulates EGFR signaling in hair morphogenesis and skin barrier formation. Cell 2010 Apr 16; doi:10.1016/j.cell.2010.03.013
Source:
Rob Graham
Children's Hospital Boston
Several known factors regulate the growth and specialization of cells in the epidermis. Two key players are transforming growth factor alpha (TGF-alpha) and the receptor for epidermal growth factor (EGFR). Without them, mice have wavy hair; when they are over-active, mice are hairless and develop skin cancer. However, these growth factors don't make ideal targets for a drug treatment since they are found throughout the body, and any drug targeting them would have substantial side effects.
The new study, led by David Clapham, MD, PhD, of Children's Hospital Boston, and Haoxing Xu, PhD, of the University of Michigan, finds that another protein found mainly in skin, TRPV3, "supercharges" the TGF-alpha/EGFR pathway. When TRPV3 was knocked out, the mice had a thinner outer skin layer with a dry, scaly texture, and appeared to be a less intact, more permeable barrier. By comparison, the normal mice formed a thick, robust outer skin barrier, with more tightly linked, toughened cells (a process known as cornification).
The mice lacking TRPV3 also developed a wavy coat and curly whiskers. Clapham believes the waviness resulted from abnormal functioning of the epidermal cells at the base of the hair follicle, normally rich in TRPV3, causing the follicles to point in different directions and preventing them from smoothly extruding hair.
TRVP3 is an ion channel, a small pore that opens to admit calcium ions into the cell. Experiments showed that it is activated by EGFR, causing an influx of calcium that triggers many signaling pathways inside the cell, including one that stimulates release of TGF-alpha. This, in turn, increases EGFR signaling, providing a positive feedback loop that "supercharges" the system. When TRPV3 was knocked out, TGF-alpha/EGFR signaling was impaired.
Clapham speculates that drugs that stimulate TRPV3 activity may offer a new approach to treating multiple skin conditions, such as burns, bed sores, eczema, psoriasis, itch, fungal infections and oral mucositis (a sloughing off of skin in the mouth due to cancer chemotherapy). It might also be possible to develop cosmetic treatments that make the skin more firm, pliable and youthful. "If you activate TRPV3, you might get thicker skin," he says.
On the flip side, reducing TRPV3 activity could curb uncontrolled cell growth in skin cancer. "Some skin cancers may be potentiated by TRPV3," says Clapham.
A more speculative possibility is that TRPV3 could be targeted to create hair growth or hair removal agents, he adds.
Unlike growth factors, which act in many tissues and can have significant side effects, TRPV3 is found mainly in skin keratinocytes, although it is also found in the brain. Because TRPV3 has also been found to play a role in pain sensation, pharmaceutical companies have already been developing small molecule drugs targeting it.
The study was funded by the Howard Hughes Medical Institute, the National Institutes of Health and the University of Michigan. Xiping Cheng, PhD, of the University of Michigan and Jie Jin, PhD, of Children's Hospital Boston were first authors.
Citation:
Cheng X et al. TRP Channel regulates EGFR signaling in hair morphogenesis and skin barrier formation. Cell 2010 Apr 16; doi:10.1016/j.cell.2010.03.013
Source:
Rob Graham
Children's Hospital Boston
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