News Article | May 18, 2017
Science will have a bigger voice in the next French government. Newly elected President Emmanuel Macron announced yesterday that a molecular geneticist–turned–university administrator will head the new ministry of higher education, research, and innovation, while a highly respected physician-scientist is France’s new health minister. Both are women—as is fully half of the new cabinet. But perhaps the biggest surprise was the appointment of the immensely popular green activist Nicolas Hulot at the new Ministry of “Ecological and Solidarity-based Transition.” Hulot—who has called Donald Trump’s retreat from the Clean Power Plan “a crime against humanity” and who wants to phase out nuclear energy—is credited with major changes in French environmental policy in the past decade—but always from outside the government. Frédérique Vidal, 53, the new research minister for science, spent most of her career at the University of Nice Sophia Antipolis, where she increasingly focused on education and climbed through the administrative ranks until becoming university president in 2012. The fact that Vidal “knows the sector … is a good thing,” says Patrick Monfort, secretary general of SNCS-FSU, a trade union for researchers based near Paris. The French Conference of University Presidents (CPU) welcomed Vidal’s appointment in a public statement yesterday. CPU says it's also an “excellent signal to the university community” that research and higher education once again have a full-fledged ministry, after being relegated to the level of secretary of state by former President François Hollande in 2014. Macron, who has promised to kick-start the economy through science, also added the word “innovation” to the ministry’s title. The other researcher in the new administration is Agnès Buzyn, who will head the health ministry—a post Macron had promised to give to a physician. Aged 54, Buzyn spent most of her career as a clinical hematologist studying leukemia and bone marrow transplantation at Paris Descartes University and the Necker Hospital. A former president of the French National Cancer Institute, Buzyn has played many high-level science policy roles and is highly respected among her peers. But as French newspaper reported yesterday, some have criticized her for questioning the need for scientists working with the pharmaceutical industry to declare their conflicts of interest. And as it happens, she has a bit of a conflict herself: Buzyn is married to Yves Lévy, who leads the €1 billion French National Institute of Health and Medical Research (INSERM), which is jointly overseen by the research and health ministries. Le Monde reports that Buzyn will not handle any issues related to INSERM, but details of the arrangement are unclear. As the paper points out, the ministry interacts with the institute on an almost daily basis. Meanwhile, the appointment of Hulot, 62, has excited French friends of the environment. A former nature documentary maker, Hulot arrived at the first cabinet meeting today in an electric car and without a tie. He instigated the inclusion of an environmental charter in the French constitution in 2005 and triggered a national policy debate that led to two new environmental laws in 2008 and 2010 that seek to drastically reduce greenhouse gas emissions, promote renewable energy, and better regulate pesticides. As a special envoy of the French president for the protection of the planet, he helped prepare the 2015 Paris climate conference. According to French newspaper yesterday, Hulot hopes to reform the tax system to make production and consumption more sustainable, and to set in motion a transition toward sustainable energy. He also wants to start a national debate on sustainable food production. Hulot toyed with the idea of running for president himself in the last three presidential elections, but has repeatedly declined positions in previous governments. The big question is how much of his agenda he can deliver in Macron’s centrist administration, however. Monfort—who studies the impact of climate change on pathogenic water bacteria at the University of Montpellier—hopes Hulot’s nomination means that he “has secured some guarantees” about what he will be able to do. Update, 19 May, 6.30 a.m.: The paragraph about Buzyn's conflict of interest has been updated.
News Article | May 15, 2017
Genomic Vision (Paris:GV) (Euronext: FR0011799907 – GV), a company specialized in the development of diagnostic tests for the early detection of cancers and genetic diseases, today reports of its first R&D Day who took place on May 10, to the Imagine Institute (Necker Hospital) in Paris, in front of a panel of individual and institutional investors, financial analysts and journalists. This first event was aimed at presenting a global overview of the IVD activities of the Company with its historical industrial partner Quest Diagnostics and with several academic teams. During an inaugural speech, Stanislas Lyonnet, Ph.D., head of Imagine Institute, directeur de l’Institut Imagine, called back the commitment of the Institute in the research on genetic pediatric diseases and the outlines of the partnership with Genomic Vision. “Our Institute is a reference center for the molecular combing technology use since almost two years. This technology can meet our stringent requirements: establish a precise and early diagnosis of the pathology, identify the genes and the mechanisms involved, evaluate the different therapeutic options and transform the patient’s healthcare.” Subsequently, Jay Wohlgemuth, M.D., Senior VP, CMO of Quest Diagnostics and Edward Ginns, M.D, Ph.D, Medical director - Neurology of Quest Diagnostics, presented the move of Quest strategy from a lab company to an added value diagnostic service provider and reminded the importance for Quest of investing in new products and technologies. He therefore insisted on the strong link between both companies by using the molecular combing technology as well as co-developing diagnostic tests. Jay Wohlgemuth declared: “We at Quest Diagnostics have been collaborating with GV for over seven years and we are highly committed to our collaboration through providing samples and data to develop applications for the DNA combing technology. Applications take the form of biomarkers for pharmaceutical development and as a clinical diagnostics tool for genetic diseases. Our first success is the development of the FSHD combing testing as a standard in the U.S. I’m committed to continue our collaboration with GV.” About the development of the BRCA test in the breast and ovarian cancer early detection, Jay Wohlgemuth specified: “The DNA combing technology has been used to explore a BRCA test for hereditary breast and ovarian cancer. We are currently performing a clinical study with GV using Quest Diagnostic’s samples and that process is ongoing. When data is available, it will be made public.” Aaron Bensimon, CEO and co-founder of Genomic Vision, indicated: « For the development of such a predisposition test, the environment profoundly evolved during the last years. BRCA test was initiated in 2012 and we had focused our analysis on the large rearrangements of BRCA1 and BRCA2 genes. Today, we know that the screening tests for breast hereditary cancer are evaluating a wider panel of more than 30 genes. Our partner Quest Diagnostics and Genomic Vision have to reposition the BRCA test on this basis and this is on what we work at the moment.” On the SMA diagnostic test, the representatives of Quest Diagnosis explained: “SMA, spinal muscular atrophy, is an hereditary complex disease with a large portion of healthy carrier of the recessive gene responsible for one of the most common muscular dystrophies in the US and around the world. Through our collaboration with Genomic Vision we believe that we will be able to uncover biomarkers crucial to the detection of potential carriers of this disease. To achieve Quest Diagnostics are collaborating through the provision of samples to fully characterize the SMA genomic region. This work is ongoing and we hope to have results over the coming year.” Pr Nicolas Levy, Head of Medical Genetics department at the Children's Hospital La Timone (Marseille, France) was next to speak for its presentation on the diagnostic approaches in FSHD by molecular combing use. « Facioscapulohumeral Muscular Dystrophy, the 3rd most spread myopathy, is perfect to demonstrate the benefits of the molecular combing technology. This one allows to update the genetic complexity of this disease while the other technologies currently used, including Next-Generation sequencing ones, don’t answer all the expectations. Off course, these NGS will evolve in the future but in our department we study pathologies which remain undetectable by them. Moreover, the molecular combing allows research in other pathologies, as the children leukemia”. Finally, Dr Petr Janda, CEO of PCS (Prague Clinical Services), the CRO in charge of the HPV clinical trial in Czech Republic and Dr Anne Jacquet, Director of Biomedical Research of Genomic Vision, presented the interim results of EXPL-HPC-002 study (http://www.genomicvision.com/wp-content/uploads/CP_GV_10-mai_HPV_FINAL-1.pdf). Dr Petr Janda reminded: “The current diagnosis tests of the cervical cancer are limited in terms of sensibility or specificity.” Beyond the promising results presented by the Genomic Vision’s HPV test, both speakers explained: “The use of the molecular combing allowed, for the first time, to visualize, to characterize and to quantify the number of HPV genomes integrated in the DNA of the female patients. This opens a new way in the diagnosis and the follow-up of the patients having a risk of cervical cancer associated with HPV virus by allowing the selection between the patients who are infected by the HPV virus but who will naturally eliminate it without developing a cancer and those who will require an appropriate care considering the rates of virus integration.” Through the presentation of the different IVD programs of Genomic Vision, Aaron Bensimon concluded: “The use of molecular combing presents a new paradigm on a large range of applications. This potential encourages us to build closer relationships with the clinicians, who are at the heart of the diagnosis of the genetic diseases and facing its deadlocks. Thanks to closer relationships with clinicians, we will be able to develop new tests, like we are doing for the SMA test." The whole conference of the R&D Day will be available for consultation on the Genomic Vision’s website in a few days. ABOUT GENOMIC VISION GENOMIC VISION is a company specialized in the development of diagnostic solutions for the early detection of cancers and serious genetic diseases and tools for life sciences research. Through the DNA Molecular Combing, a strong proprietary technology allowing to identify genetic abnormalities, GENOMIC VISION stimulates the R&D productivity of the pharmaceutical companies, the leaders of the diagnostic industry and the research labs. The Company develops a robust portfolio of diagnostic tests (breast, ovarian and colorectal cancers, myopathies) and analysis tools (DNA replication, biomarkers discovery, gene editing quality control). Based near Paris, in Bagneux, the Company has approximately 60 employees. GENOMIC VISION is a public listed company listed in compartment C of Euronext’s regulated market in Paris (Euronext: GV - ISIN: FR0011799907). For further information, please visit www.genomicvision.com This press release contains implicitly or explicitly certain forward-looking statements concerning Genomic Vision and its business. Such forward-looking statements are based on assumptions that Genomic Vision considers to be reasonable. However, there can be no assurance that such forward-looking statements will be verified, which statements are subject to numerous risks, including the risks set forth in the “Risk Factors” section in its Document de Reference filed with the French Autorité des Marchés Financiers (AMF) on March 28, 2017, under number R.17-009, available on the web site of Genomic Vision (www.genomicvision.com) and to the development of economic conditions, financial markets and the markets in which Genomic Vision operates. The forward-looking statements contained in this press release are also subject to risks not yet known to Genomic Vision or not currently considered material by Genomic Vision. The occurrence of all or part of such risks could cause actual results, financial conditions, performance or achievements of Genomic Vision to be materially different from such forward-looking statements. This press release and the information contained herein do not constitute and should not be construed as an offer or an invitation to sell or subscribe, or the solicitation of any order or invitation to purchase or subscribe for Genomic Vision shares in any country. The distribution of this press release in certain countries may be a breach of applicable laws. The persons in possession of this press release must inquire about any local restrictions and comply with these restrictions.
Lapillonne A.,University of Paris Descartes |
Lapillonne A.,Baylor College of Medicine |
Lapillonne A.,Necker Hospital |
Griffin I.J.,University of California at Davis
Journal of Pediatrics | Year: 2013
Preterm birth continues to contribute disproportionately to neonatal morbidity and subsequent physical and neurodevelopmental disabilities. Epidemiologic studies have described additional long-term health consequences of preterm birth such as an increased risk of hypertension and insulin resistance in adult life. It is not known whether the influence of infant and childhood growth rates and early nutrition on long-term outcomes is the same or different among preterm infants and neonates with intrauterine growth restriction. Our goal is to review the effects of fetal growth, postnatal growth, and early nutrition on long-term cardiovascular and metabolic outcomes in preterm infants. Present evidence suggests that even brief periods of relative undernutrition during a sensitive period of development have significant adverse effects on later development. Our review suggests that growth between birth and expected term and 12-18 months post-term has no significant effect on later blood pressure and metabolic syndrome, whereas reduced growth during hospitalization significantly impacts later neurodevelopment. In contrast, growth during late infancy and childhood appears to be a major determinant of later metabolic and cardiovascular well being, which suggests that nutritional interventions during this period are worthy of more study. Our review also highlights the paucity of well-designed, controlled studies in preterm infants of the effects of nutrition during hospitalization and after discharge on development, the risk of developing hypertension, or insulin resistance.
bluebird bio Presents New Data from HGB 205 Study of LentiGlobinTM Drug Product in Patients with Transfusion Dependent Thalassemia TDT and Severe Sickle Cell Disease at American Society of Hematology ASH Annual Meeting
News Article | December 3, 2016
SAN DIEGO--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, announced the presentation of new data from the ongoing HGB-205 clinical study evaluating its LentiGlobin product candidate in patients with transfusion-dependent β-thalassemia (TDT) and severe sickle cell disease (SCD) at the 58th American Society of Hematology Annual Meeting. The data from the HGB-205 study were highlighted today in a poster presentation by Marina Cavazzana, M.D., Ph.D., lead investigator of the HGB-205 study conducted in Necker Hospital, AP-HP and professor of hematology at Paris Descartes University, head of the department of Biotherapy Hospital, the clinical research center of Biotherapy at Necker Enfants Malades - Greater Paris University Hospitals, AP-HP and Inserm) and the Lymphohematopoiesis Laboratory, Institute of Genetic Diseases, Imagine, Paris, France. “We believe the enduring responses seen in this study - in the patients with TDT as well as the patient with SCD - demonstrate the continued promise of LentiGlobin gene therapy in both of these patient populations. We have seen nearly three years of transfusion independence in TDT in certain patients, providing important data on the long-term safety and durability of this therapy,” said David Davidson, M.D., chief medical officer, bluebird bio. “In addition, it is encouraging that the patient with SCD has remained free of acute SCD-related clinical events in the 21 months since treatment, when he previously required monthly blood transfusions to help control his SCD symptoms. This patient’s successful outcome not only offers hope for the potential of LentiGlobin to benefit other patients with SCD, but also provides important insights into this complex disease that we are applying to our ongoing HGB-206 study.” Abstract #2311: Update from the HGB-205 Phase 1/2 Clinical Study of LentiGlobin Gene Therapy: Sustained Clinical Benefit in Severe Hemoglobinopathies HGB-205 is an ongoing, open-label, single-center Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product in the treatment of patients with TDT and severe SCD. Four patients with TDT and one patient with severe SCD have undergone infusion with LentiGlobin drug product in this study as of September 9, 2016. The patients with TDT have between 11.6 and 33.5 months of follow-up, and the patient with SCD has 22.9 months of follow-up. “These data show a stable clinical and biological effect in patients with TDT or severe SCD who have received a one-time treatment with LentiGlobin,” said Professor Cavazzana. “We are now seeing the benefit of gene therapy with LentiGlobin beyond two years in TDT in certain patients, and clinical benefit continues to be realized in the patient with severe SCD after almost 24 months of follow-up. We are encouraged by these results and the potential benefit treatment with LentiGlobin can have on patients living with these debilitating diseases and without an HLA compatible sibling donor.” bluebird bio will host a live webcast at 8:30 p.m. PT (11:30 p.m. ET) on Monday, December 5, 2016. The live webcast can be accessed under "Calendar of Events" in the Investors and Media section of the company's website at www.bluebirdbio.com. With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ BB305 product candidate, currently in four clinical studies for the treatment of transfusion-dependent β-thalassemia and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in lentiviral gene delivery and T cell engineering, with a focus on developing novel T cell-based immunotherapies, including chimeric antigen receptor (CAR T) and T cell receptor (TCR) therapies. bluebird bio’s lead oncology program, bb2121, is an anti-BCMA CAR T program partnered with Celgene. bb2121 is currently being studied in a Phase 1 trial for the treatment of relapsed/refractory multiple myeloma. bluebird bio also has discovery research programs utilizing megaTALs/homing endonuclease gene editing technologies with the potential for use across the company’s pipeline. This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s research, development, manufacturing and regulatory approval plans for its LentiGlobin product candidate to treat transfusion-dependent ß-thalassemia and severe sickle cell disease. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks that the preliminary positive results from our prior and ongoing clinical trials of LentiGlobin, including HGB-205, will not continue or be repeated in our ongoing or planned clinical trials of LentiGlobin, the risks that the changes we have made in the LentiGlobin manufacturing process or the HGB-206 clinical trial protocol will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin will be insufficient to support regulatory submissions or marketing approval in the US and EU, the risk of a delay in the enrollment of patients in our clinical studies, and the risk that any one or more of our product candidates will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law. About AP-HP: AP-HP - Greater Paris University hospitals - is a European world-renowned European university hospital. Its 39 hospitals treat 8 million people every year: in consultation, emergency, during scheduled or home hospitalizations. The AP-HP provides a public health service for everyone, 24 hours a day. This mission is a duty as well as a grzeat source of pride. The AP-HP is the leading employer un the Greater Paris area : 100 000 staff members – doctors, researchers, paramedical staff, administrative personnel and workers – work there. http://www.aphp.fr About the Imagine Institute: As the leading European center for research, care and teaching in genetic diseases, the Imagine Institute's primary aim is to understand and cure. The Institute's staff includes 850 of the best physicians, scientists and healthcare professionals housed in an innovative new building designed to realize synergies. This unprecedented continuum of expertise available in close proximity to patients allows Imagine to accelerate discoveries and their application at the bedside. www.institutimagine.org
News Article | March 1, 2017
CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, today announced the publication in the New England Journal of Medicine of a case study on Patient 1204, the first patient with severe sickle cell disease (SCD) to be treated with gene therapy. This patient, who was 13 years old at the time of treatment, was treated with LentiGlobin drug product in the HGB-205 clinical study conducted in Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. The data in the publication reflect 15 months of follow-up, and a brief summary of this patient’s outcomes with 21 months of follow-up was presented at the 58th American Society of Hematology Annual Meeting in December 2016. “We have managed this patient at Necker for more than 10 years, and standard treatments were not able to control his SCD symptoms. He had to receive blood transfusions every month to prevent severe pain crises,” said Professor Marina Cavazzana, M.D., Ph.D., principal investigator of this study and professor of hematology at Paris Descartes University, head of the department of Biotherapy Hospital, the clinical research center of Biotherapy at Necker Enfants Malades - Greater Paris University Hospital, AP-HP and INSERM, and of the Lymphohematopoiesis Laboratory, Imagine Institute of Genetic Diseases, Paris, France. “Since receiving the autologous stem cell transplant with LentiGlobin, he has been free from severe symptoms and has resumed normal activities, without the need for further transfusions.” “Since our initial publication of this therapeutic approach in mouse models in 2001, we are delighted to obtain such a clear proof-of-principle of its efficacy in a patient,” said Philippe Leboulch, M.D. Dr. Leboulch is professor of medicine at the University Paris-Sud and High Counselor and International Scientific Director at France’s CEA. He was a scientific founder of bluebird bio and serves as the co-chairman of its Scientific Advisory Board. Dr. Leboulch led the development of the anti-sickling T87Q globin vector used in LentiGlobin. “We are pleased to see this case study published in NEJM and shared with the broader research community. The successful outcome in Patient 1204 demonstrates the promise of treatment with LentiGlobin gene therapy in patients with severe SCD and serves as a guide for our efforts to optimize outcomes in future patients,” said David Davidson, M.D., chief medical officer, bluebird bio. “By analyzing this patient’s experience, we have identified key variables to optimize in our ongoing HGB-206 study of LentiGlobin gene therapy in severe SCD, and we are hopeful that these protocol changes will enable subsequent patients to achieve the transformative benefit seen in Patient 1204.” Clinical and Biological Outcomes for the First Patient with Sickle Cell Disease Treated with Gene Therapy Patient 1204, a male patient with βS/βS genotype, was enrolled in May 2014 at 13 years of age into the HGB-205 clinical study. The patient underwent a regular transfusion regimen for 4 years prior to this study. He had an average of 1.6 SCD-related events annually in the 9 years prior to initiating transfusions, and his complications from SCD included vaso-occlusive crises, acute-chest syndrome, bilateral hip osteonecrosis, and cerebral vasculopathy. The patient underwent two bone marrow harvests to collect hematopoietic stem cells (HSCs) for gene transfer and back-up (6.2×108 and 5.4×108 total nucleated cells/kg harvested). CD34+ cells were enriched from the harvested marrow and then transduced with LentiGlobin BB305 lentiviral vector. The vector copy numbers (VCN; vector copies per diploid genome) for the drug product lots manufactured were 1.0 and 1.2. The patient underwent myeloablation with intravenous busulfan (2.3 to 4.8 mg/kg per day for 4 days) with daily pharmacokinetic studies and dose adjustment. Total busulfan area under the curve (AUC) was 19,363 μmol*min. After a 2-day washout, Patient 1204 was infused with LentiGlobin drug product in October 2014 at a post-thaw total dose of 5.6×106 CD34+ cells/kg. RBC transfusions were to be continued after transplantation until a sufficient proportion of HbAT87Q (25-30% of total Hb) was detected. Neutrophil and platelet engraftment were achieved on Day +38 and Day +91 post-transplantation, respectively. HbAT87Q levels increased steadily and RBC transfusions were discontinued after the last transfusion on Day +88. HbAT87Q reached 5.5 g/dL (46% of total Hb) at Month 9 and continued to increase to 5.7 g/dL at Month 15 (48%), with a reciprocal decrease in HbS levels to 5.5 g/dL (46%) at Month 9, and 5.8 g/dL (49%) at Month 15. Total Hb levels have been stable between 10.6 and 12.0 g/dL since Month 6 post-transplant. HbF levels have remained below 1.0 g/dL. Adverse events (AEs) were consistent with busulfan conditioning, and no AEs related to LentiGlobin drug product have been observed to date. Over the 15 months since transplantation, no SCD-related clinical events or hospitalizations have occurred, contrasting favorably with the period before the patient began regular transfusions. All medications have been discontinued, including pain medication. The patient has resumed regular school attendance and reports full participation in normal physical activities. About SCD Sickle cell disease (SCD) is an inherited disease caused by a mutation in the β-globin gene that results in sickle-shaped red blood cells. The disease is characterized by anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life and, sometimes, early death. Where adequate medical care is available, common treatments for patients with SCD largely revolve around management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced therapy for SCD is allogeneic hematopoietic stem cell transplantation (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft-versus-host disease, and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT. About bluebird bio, Inc. With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ BB305 product candidate, currently in four clinical studies for the treatment of transfusion-dependent β-thalassemia and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in lentiviral gene delivery and T cell engineering, with a focus on developing novel T cell-based immunotherapies, including chimeric antigen receptor (CAR) and T cell receptor (TCR) therapies. bluebird bio’s lead oncology program, bb2121, is an anti-BCMA CAR T program partnered with Celgene. bb2121 is currently being studied in a Phase 1 trial for the treatment of relapsed/refractory multiple myeloma. bluebird bio also has discovery research programs utilizing megaTAL/homing endonuclease gene editing technologies with the potential for use across the company’s pipeline. About AP-HP AP-HP - Greater Paris University hospitals - is a European world-renowned university hospital. Its 39 hospitals treat 8 million people every year: in consultation, emergency, during scheduled or home hospitalizations. The AP-HP provides a public health service for everyone, 24 hours a day. This mission is a duty as well as a great source of pride. The AP-HP is the leading employer in the Greater Paris area: 100,000 staff members – doctors, researchers, paramedical staff, administrative personnel and workers – work there. http://www.aphp.fr About the Imagine Institute As the leading European center for research, care and teaching in genetic diseases, the Imagine Institute's primary aim is to understand and cure. The Institute's staff includes 850 of the best physicians, scientists and healthcare professionals housed in an innovative new building designed to realize synergies. This unprecedented continuum of expertise available in close proximity to patients allows Imagine to accelerate discoveries and their application at the bedside. www.institutimagine.org Forward-Looking Statements This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s research and development plans for its LentiGlobin product candidate to treat severe sickle cell disease, including statements whether the manufacturing process changes for LentiGlobin will improve outcomes of patients with severe sickle cell disease and whether the planned changes to the HGB-206 clinical trial protocol will improve outcomes in patients with severe sickle cell disease. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials of LentiGlobin will not continue or be repeated in our ongoing, planned or expanded clinical trials of LentiGlobin, the risks that the changes we have made in the LentiGlobin manufacturing process or the HGB-206 clinical trial protocol will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin will be insufficient to support regulatory submissions or marketing approval in the US and EU, the risk of a delay in the enrollment of patients in our clinical studies, and the risk that any one or more of our product candidates will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent quarterly report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.
Chiron C.,French Institute of Health and Medical Research |
Chiron C.,Necker Hospital |
An I.,Pitie Salpetriere Hospital
Epilepsia | Year: 2014
Contrary to the treatment concerns regarding drug compliance or pregnancy at transition to adulthood, those directly related to epilepsy remain poorly documented. As an initial step to answer this problem, we reviewed the controlled trials of antiepileptic drugs (AEDs) independently performed in adults and children for a given syndrome. Then we reviewed the longitudinal long-term course in the various epilepsy syndromes. Optimizing AED treatment at adulthood might be beneficial, even after many years of pharmacoresistance. Finally we retrospectively reviewed our personal series of 39 patients with specific pharmacoresistant epilepsy syndromes, who transferred from pediatric to adult care between 2005 and 2012. In 26 of the patients, AEDs were modified and, we reduced seizure frequency in 62% of them, including highly refractory patients. By contrast, AED changes in six controlled patients (for pregnancy anticipation or vigabatrin-related retinal toxicity) led to severe seizure relapse. Further studies are needed to elaborate guidelines in pharmacoresistant syndromes during transition and after transfer to adult care. © 2014 International League Against Epilepsy.
Loupy A.,Necker Hospital |
Hill G.S.,Georges Pompidou European Hospital |
Jordan S.C.,Cedars Sinai Medical Center
Nature Reviews Nephrology | Year: 2012
Despite improvements in outcomes of renal transplantation, kidney allograft loss remains substantial, and is associated with increased morbidity, mortality and costs. Identifying the pathologic pathways responsible for allograft loss, and the attendant development of therapeutic interventions, will be one of the guiding future objectives of transplant medicine. One of the most important advances of the past decade has been the demonstration of the destructive power of anti-HLA alloantibodies and their association with antibody-mediated rejection (ABMR). Compelling evidence exists to show that donor-specific anti-HLA antibodies (DSAs) are largely responsible for the chronic deterioration of allografts, a condition previously attributed to calcineurin inhibitor toxicity and chronic allograft nephropathy. The emergence of sensitive techniques to detect DSAs, together with advances in the assessment of graft pathology, have expanded the spectrum of what constitutes ABMR. Today, subtler forms of rejection-such as indolent ABMR, C4d-negative ABMR, and transplant arteriopathy-are seen in which DSAs exert a marked pathological effect. In addition, arteriosclerosis, previously thought to be a bystander lesion related to the vicissitudes of aging, is accelerated in ABMR. Advances in our understanding of the pathological significance of DSAs and ABMR show their primacy in the mediation of chronic allograft destruction. Therapies aimed at B cells, plasma cells and antibodies will be important therapeutic options to improve the length and quality of kidney allograft survival. © 2012 Macmillan Publishers Limited. All rights reserved.
D'Agostino M.A.,University of Versailles |
D'Agostino M.A.,Necker Hospital
Best Practice and Research: Clinical Rheumatology | Year: 2010
Through recent technological advances, ultrasound allows high-resolution visualisation of inflammatory and destructive changes in tendon and joint structures. Over the last few years, the added value of the use of ultrasound for evaluating entheseal involvement in spondyloarthritis (SpA) patients has been demonstrated. Several studies have described the ultrasound features of enthesitis in SpA, revealing the high frequency of clinically asymptomatic abnormal findings. It is, therefore, highly relevant to consider the validity of ultrasonographic measures of entheseal inflammation and damage. This article focusses on ultrasound appearance of peripheral enthesitis, and underlines the advantages and current limitations of the technique for the management of SpA. © 2010 Elsevier Ltd. All rights reserved.
Helal I.,Necker Hospital
Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia | Year: 2011
Renal insufficiency is a common complication early after hematopoietic cell transplantation (HCT). We retrospectively examined the incidence, risk factors and associated mortality of acute renal failure (ARF) in a cohort of 101 consecutive allogeneic HCT patients. These patients were reviewed to determine their baseline characteristics, the presence of co-morbid conditions and mortality rates at one year. ARF was defined by the doubling of the baseline serum creatinine (Scr) levels. The mean age of the 101 study patients was 34 ± 11.8 years. Of them, 58 (57.4%) had ARF, yielding an incidence of 2.6% per week during the first year following HCT. The peak frequency of ARF occurred during the second week (29.3%). The need for hemodialysis, a proof of the severity of ARF, was seen in 12 cases (20.7%). On univariate analysis, the Scr at one month greater than 90 μmol/L (P = 0.008), use of aminoglycosides (P < 10 -3 ), the presence of veno-occlusive disease (VOD) (P < 10 -3 ) and the need for admission to the intensive care unit (ICU) (P = 0.003) were associated with a significantly increased risk of ARF. On multivariate analysis, the independent variables associated with an increased risk for ARF were the presence of VOD [P = 0.07, relative risk (RR) = 2.06] and use of aminoglycosides (P < 10 -3 , RR = 11.2). The overall mortality rate among the study patients was 35.6% at the end of the first year. On multivariate analysis, only the use of aminoglycosides (P = 0.02, RR = 0.31), admission to the ICU (P < 10 -3, RR = 7.29) and the development of ARF (P = 0.001, RR = 8.97) were independent predictors of mortality. Our study shows that ARF is highly prevalent during the early period following HCT and increases mortality, particularly if dialysis dependent. It frequently occurs following VOD and aminoglycoside use. As the prognosis is rather grim, it is very important that the associated factors be identified early, for an effective prevention of this disease.
Ouss L.,Necker hospital |
Tordjman E.,Necker hospital
Neurophysiologie Clinique | Year: 2014
This paper aims to describe current questions concerning conversive disorders among children and adolescents. We first describe prevalence and clinical characteristics of these. Many unresolved questions remain. Why do patients show excess, or loss of function? Attachment theory offers a relevant framework to answer this question. Does neurobiology of conversion disorders shed light on conversive processes? Current neurobiological research paradigms focus on the symptom, trying to infer processes, instead of proposing paradigms that test theoretical hypotheses. The most convincing theoretical framework that has already proposed a coherent theory of conversion is a psychodynamic one, which has not yet been tested with neurobiological paradigms. The interest of studying child and adolescent conversive disorders is to provide a means to more deeply investigate the two challenges we face: theoretical, and clinical ones. It provides the opportunity to access a pathopsychological process at its roots, not yet hidden by many defensive, rationalizing attitudes, and to better explore environmental features. We propose a "complementarist" model, which allows the combination of different approaches (neural, cognitive, environmental, attachment, intra-psychic) and permits proposal of different levels of therapeutic targets and means. © 2014 Elsevier Masson SAS.