An innovative treatment to double the lifespan of cardiac valve substitutes.

July 2017. An innovative treatment to double the lifespan of animal-derived cardiac valve substitutes. This is what BCI, BioCompatibility Innovation, an innovative startup based in Padua, is developing. It involves two biologists with academic experience and has already secured €700,000 in funding. In September, the first official trial will begin in collaboration with the Policlinico Universitario Gemelli in Rome.

Combatting calcification

At the core of the process developed by Alessandro Gandaglia and Filippo Naso is the inactivation of the alpha-Gal molecule, which triggers adverse reactions in current biological cardiac valve prostheses (bioprostheses). “The alpha-Gal antigen is a small molecule expressed in all mammals except humans. Even the animal tissues used for the manufacture of current cardiac valve substitutes (mainly pig and cattle) possess this characteristic,” explains Filippo Naso. “This molecule is the main cause of immunological reactions leading to degeneration and dysfunction of the implanted valve bioprosthesis. The human body produces large quantities of antibodies directed against this molecule in order to eliminate it and, with it, eliminate the source from which it originates, namely the animal tissue of which the valve is composed.”

The adverse reaction to the alpha-Gal antigen affects all bioprosthesis carriers: in 50% of cases, it induces calcifications that necessitate valve replacement on average after 10 years of implantation. Calcification also develops more rapidly if the transplanted patient is young. Currently available bioprostheses are chemically treated to create a shield between alpha-Gal and the immune system, but they fail to effectively resolve the problem. Calcification thus proceeds slowly but inexorably. Indeed, below the age of 35, replacement is necessary after only five years from the initial implant for 100% of patients; above 35 years, in 50% of cases, a new intervention is necessary after approximately ten to twelve years. Considering that the maximum number of valve replacements that can be performed over a lifetime is 2 or 3, it is understood how this problem directly affects the quality of life of these patients.

Innovation for valves 

BCI has developed a valve treatment methodology – called FACTA – subject to an international patent application, the results of which were presented to the scientific community through a publication in the “Tissue Engineering Part A” journal on May 10 of last year. The uniqueness of this treatment lies in its ability to disarm the alpha-Gal antigen and consequently inhibit calcification processes by over 85%. In laboratory tests, the treatment has also demonstrated the ability to make tissues more mechanically resistant.

The economic factor

The implications of the applications of this process are very significant both economically and medically. Animal-derived prostheses are much more widely used than mechanical or those derived from deceased donors. “Last year, worldwide, 400,000 animal-derived cardiac valve prostheses were sold. The total expenditure for patient management was estimated at around $14 billion in 2016, due to new valve replacement surgeries and those necessary for the deterioration of already implanted bioprostheses. The technology developed by BCI, aimed at prolonging the lifespan of the bioprostheses themselves, as well as ensuring a significant reduction in the rate of surgical reintervention, will guarantee a significant saving in public healthcare expenditure,” concludes Alessandro Gandaglia.

The BCI team

BCI consists of: Filippo Naso, Scientific Director, a graduate in Biotechnology with ten years of research experience at the University of Padua in the field of Tissue Engineering and Cardiovascular Regenerative Medicine, and Alessandro Gandaglia, General Manager, a former scientific researcher at Italian and American universities who subsequently gained managerial experience in various biomedical companies, and Ugo Stefanelli, a general practitioner from Padua and entrepreneur.