Heart valve disease is one of the main causes of morbidity and mortality worldwide.
In 2017, around 400.000 patients underwent heart valve replacement; this incidence is expected to exceed 850.000 units in 2050. When a heart valve is no longer able to perform its function (due to congenital factors, various diseases or due to of ageing) it must be replaced surgically. Prosthetic heart valves substitutes are classified into two main categories: Mechanical (MHVs) and Bioprosthetic Heart Valves (BHVs, including tissue and transcatheter heart valves) . Although MHVs last longer, they are composed of thrombogenic material and therefore patients with MHV require lifetime anticoagulation therapy, which increases the risk of bleeding, haemorrhage, anaemia and renal disease. About 50% of the implanted prosthetic heart valves in the world are biological since they have better biocompatibility, do not require lifelong anticoagulant therapy and show a more physiological hemodynamics . In order to guarantee immunological tolerance, the adequate mechanical resistance and conservation over time, current BHVs are subjected by manufacturing companies to chemical treatment with cross-linking agents such as glutaraldehyde (GLU), but unfortunately their durability is limited due to onset of calcific degenerations that prevent their correct functionality. GLU shows limited efficacy: about half of the alpha-Gal epitopes remain available and reactive towards circulating antibodies, allowing the creation of inflammatory states which can evolve in immune-mediated reactions related to tissue calcification . These degenerative phenomena begin to affect the BHV tissue after 5 years from implantation. 50% of implanted BHVs need to be replaced 10/12 years after surgery. In the case of young patients, this duration is dramatically reduced (100% of BHVs do not exceed the tenth year of activity) . Technological evolution and new treatments/products have greatly reduced the mortality rate for people suffering from valvulopathies, but none of the current BHVs can definitively restore the native function.
Why is it important for society?
The FACTA technology developed by BCI presents several competitive advantages about both for the treatments currently applied by the BHVs manufacturers and for the possible future approaches that are still under study and development. Currently chemical treatments of BHVs manufacturers have: limited biocompatibility; immune response activation; high propensity to calcification and limited duration. Moreover, they are not recommended in young patients and entail high costs for hospitals and health facilities due to frequently new operations. The FACTA technology allows: high biocompatibility degree; low thrombogenicity; resistance to degradation phenomena; resistance to calcification and increase in duration. It is also potentially suitable for young patients and reduces costs for hospitals and health facilities avoiding new operations.
Overall Objectives:
The current project has the objective to carry out a feasibility study for FACTA, both on business and technical level:
- The business feasibility study has been focused on the validation of the BCI business model, that provides for the direct purchase of the starting animal tissue, its treatment with the FACTA method and its sale as a semi-processed product to BHV manufacturing companies.
- The technical feasibility study has been focused on the assessment of the need for a second pre-clinical trial to confirm the in-vivo inactivation of the alpha-Gal molecule. Since the recognition of the alpha-Gal by circulating anti alpha-Gal antibodies is considered a primary event that can initiate the deposition of calcium salts on the tissue, the immunological reactivity towards the treated tissue will be especially considered. If the feasibility study reveals this need as common to all the contacted BHV manufacturers, it will be necessary to evaluate times and costs of this new exper
