Ethics

The TRANSLINK project aims to provide the data to demonstrate beyond any reasonable doubt the central role of the anti-BHV immune response in the premature failure of BHV and to provide a strategy to enable safe implantation of BHV valves in currently unsuitable candidates. In detail, TRANSLINK research will be aimed at: (i) identifying both remaining and possibly novel BHV carbohydrate determinants that may elicit or be the target of anti-BHV antibodies or activate human immune cells, (ii) characterize the possible detrimental role played in BHV recipients by anti-_Gal but also anti non-_Gal antibodies whose specificities have not been previously explored, (iii) characterize the potential detrimental role played in BHV recipients by the acquired and innate cellular immune response to BHV, and (iv) development of novel preventive and therapeutic strategies to combat BHV-related adverse immune reactions.

Doctor with medical card

To achieve these goals, TRANSLINK proposes a prospective clinical and biological observational study of a multi-centre cohort of patients recruited in four large EU centers of cardiac surgery. Moreover, medical assessment of the risk associated with an immune response against the implant will be evaluated by in vitro assays (using human samples collected from BHV receiving patients) and in vivo models (involving the use of transgenic mice), which mimic relevant aspects of the clinical setting. The impact of anticarbohydrate antibodies on bacterial infections that cause most of the human prosthetic valve endocarditis will be also investigated in this project by in vitro and in vivo (rodent) models.

The project will lead to the development of novel preventive and therapeutic strategies to counteract BHV-related adverse immune reactions. Indeed, new molecules with binding capacity to protect the implant will be evaluated in vivo in appropriate animal models (CMAh-null transgenic mice and immunized rats). Moreover, the production of a novel generation of immune-resistant BHV will involve the generation of new genetic engineered pig and cattle, as a source of new “immune-resistant” device to implant in patients needing valve replacement.

The work within this consortium will, therefore, regard BHV recipient patients, including patient’s personal data, handling of human tissues and the use of experimental animals. All the aspects will be addressed in compliance with the fundamental ethical principles of respect human dignity, biomedical ethics (respect of autonomy, beneficence, non maleficience and justice) and animal ethics. All the research activities of TRANSLINK will be submitted to and approved by local ethics committees in accordance with relevant EU and National legislation and guidelines. All work will conform to the guidelines of Good Scientific Practice according to the EU regulation

Specifically, for their human and animal studies the participants of TRANSLINK will conform to the following relevant directives:

  • The “Charter of Fundamental Rights” of the European Union (2000/C 364/01)
  • The Convention of the Council of Europe on “Human Rights and Biomedicine” signed In Oviedo on April 4 1997
  • The “Additional Protocol on the prohibition of cloning Human Beings” signed in Paris on January 12 1998 and Directive 86/609 EEC.
  • The Universal Declaration on the Human Genome and the Rights of Man adopted by UNESCO on 11. November 1997
  • The Declaration on Human Genetic Data adopted by UNESCO on 16. October 2003
  • The Universal Declaration on Bioethics and Human Rights adopted by UNESCO on 19. October 2005.

The Coordinator and the project management team will: (i) ensure that all partners have the required permits or authorizations for the proposed studies that will be provided to the EU Commission, (ii) will ensure that each member of the project is adequately educated regarding the ethical issues posed by the project, to ensure that the research performed by TRANLINK partners conforms to the EU and National (Italy, Spain, France and Israel) regulations and guidelines which are relevant to this research.