Key Benefits:
Director General of the Biomedicine Agency,
Vu la Act No. 2013-715 of 6 August 2013 to amend the Act No. 2011-814 of 7 July 2011 relating to bioethics by authorizing under certain conditions research on embryo and embryonic stem cells;
Vu le Public Health Codearticles L. 2151-5 and R. 2151-1 to R. 2151-12;
In view of the decision of 17 September 2013 setting the application file model for the authorizations referred to in theArticle R. 2151-6 of the Public Health Code ;
Considering the Order of Ministers for Health and Research of 8 July 2005 and the decision of the Director General of the Biomedicine Agency of 23 April 2010 authorizing the National Institute of Health and Medical Research (Unit U1183) to implement a research protocol on human embryonic stem cells;
Considering the application submitted on 31 January 2015 by the National Institute of Health and Medical Research (Unit U1183) for the purpose of obtaining the renewal of its research protocol authorization on human embryonic stem cells;
Considering the report of the inspection mission of the Biomedicine Agency dated 23 April 2015;
Considering the expert reports of 15 April and 24 May 2015;
Having regard to the advice issued by the Guidance Board of the Biomedicine Agency on 17 September 2015;
Considering that the project concerns the development of therapeutic strategies of neurodegenerative diseases, and particularly communicable spongiform encephalopathies or prion diseases (Creutzfeldt-Jakob disease in particular) for which there is no treatment; that the Creutzfeldt-Jakob disease is characterized by a cerebral accumulation of an abnormal prion protein (PrPSc)
Considering that the team's strategy is to introduce, through a viral vector (lentivirus), in cells of the neural therapeutic stems (issues of human embryonic stem cells) of the sequences coding for mutant forms of the prion protein, unable to be converted to abnormal PrPScencias cells; that these cells will prevent the delegitimate effects of the PrPSc protein and repair the
Considering that a first authorization was granted to this team in 2005 for a period of five years and has been renewed in 2010 for an additional five years in order to obtain neural progenitors from CSEh and to validate the effectiveness of this strategy in vivo (souris) or in vitro models; that if the realization of the protocol had to be suspended due to the relocation of the laboratory in December 2011 and
Considering that during the previous authorization, the team defined the differentiation protocols in neural stem cells, then in neurons from human embryonic stem cells and validated the different stages of maturation validated by the expression of specific markers; that it has in parallel defined the conditions of transduction of CSEh and neural precursors and successfully tested its efficacy and synthesis of the corresponding proteins on the line of CSEh H1; that it has put in place an in vitro model, using slices of transgenic mouse cerebellum expressing human PrP; that the objective is to use this classical experimental model to transplant infected CSEh
Considering that the team wishes to continue its project in order to offer a therapeutic approach combining cell and gene therapy validated from an experimental point of view in Creutzfeldt-Jakob disease; that Sylvain Lehmann also plans to study the role of PrP in the biology of CSEh and during the neural differentiation of these cells, as well as the role of the APP protein, involved in Alzheimer's disease, presenting similarities with the first model;
Considering that the application is part of the continuity of the previous protocol and that it is therefore a research protocol that is part of a medical purpose;
Considering that, in the state of scientific knowledge, it cannot be carried out without resort to human embryonic stem cells; that the expected result cannot be obtained by other means, in particular by the exclusive use of other stem cells; that to the extent that the team's program is directed towards a clinical application, there is no alternative cellular product that has comparable efficacy, and that it is therefore
Considering that the use of induced pluripotent stem cell lines (iPS cells) is currently hampered by the absence of internationally validated reference lines (unlike human embryonic stem cells H1 and H9 used in this project); that there are no iPS lines of clinical grade immediately available in France (derived under GMP conditions - Good manufacturing practices
Considering the difficulty of drifting lines of patients with Creutzfeldt-Jakob disease that should be handled in a P3 laboratory because of their danger, and finally the uncertainty regarding the interactions between the reprogramming process and the abnormalities it causes;
Considering, therefore, that the applicant provides sufficient information on the scientific relevance of the research project on the one hand, and its conditions of implementation under the ethical principles on the other; that it justifies in particular that the project will be carried out in accordance with the ethical principles of research on embryo and human embryonic stem cells and that these cells have been obtained in accordance with the fundamental principles provided for in the Articles 16 to 16-8 of the Civil Code, and with the prior consent of the procuring couple, and without any payment, in any form, being allocated to them;
Considering that the titles, diplomas, experience and scientific work provided in support of the application help to ensure the skills of the research manager and the team members in this area; that the structure is sustainable and the team is internationally recognized for its work; that the latter is important, well-structured, and presents the capacities required to carry out the planned program; that it has also explored this area of research for many years;
Considering that the premises, materials, equipment, processes and techniques are adapted to the proposed research activity; that this research will be carried out in conditions that guarantee the safety of persons engaged in professional activity on the site, the respect of the applicable provisions in the field of environmental protection, the respect of the sanitary safety rules as well as the safety, quality and traceability of embryos and embryonic cells; that the material conditions of security, conservation,
Decides:
The National Institute of Health and Medical Research (Unit U1183) is authorized to implement, under the conditions described in the application for authorization, the research protocol on human embryonic stem cells whose purpose is to study the mechanisms of autorenewal and neural differentiation, their understanding of the development of therapeutic approaches to neurodegenerative diseases. This research is under the responsibility of Mr. Sylvain LEHMANN.
This authorization is granted for a period of five years. It may be suspended at any time for a maximum of three months, in the event of a violation of the legislative or regulatory provisions, by the Director General of the Biomedicine Agency. Authorization may also be withdrawn, in accordance with the terms and conditions set out in the provisions of Public Health Code.
Any changes to the elements in the application for authorization must be made available to the Director General of the Biomedicine Agency.
The Assistant Director General for Resources of the Biomedicine Agency is responsible for the execution of this decision, which will be published in the Official Journal of the French Republic.
Done on 13 October 2015.
A. Courts
