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FP7

THE GRAIL Report Summary

Project ID: 278557
Funded under: FP7-HEALTH
Country: Italy

Periodic Report Summary 3 - THE GRAIL (Tissue in Host Engineering Guided Regeneration of Arterial Intimal Layer)

Project Context and Objectives:
The ultimate objective of THEGRAIL project aims at developing a bioactive and bioresorbable scaffold for in vivo regeneration of intima layer after any treatment leading to an atherosclerotic plaque ablation from the obstructed arteries in patients suffering from occlusive coronary or peripheral arterial diseases.
THEGRAIL technology does not intend to stent the artery; conversely, it aims to replace the diseased and stiffened area with a soft and compliant intelligent scaffold (name Synthetic Intima Layer – SIL) that will reabsorb once its task is completed, leaving a physiologically responsive regenerated tissue.
The invention relies on two main innovations:
INN 1. Smart polymers based on Elastin Like Polymers (rELP) to produce bioactive and bioresorbable scaffolds capable to induce regeneration of intima layer in vivo by means of recruiting patient circulating endothelial cells and adhere to the arterial media. THEGRAIL Project is based on the use of recombinant Elastin Like Polymers (rELP) that display Inverse Temperature Transition (ITT) feature. rELP are completely water soluble under their specific transition temperature (Tt) and switch to hydrogel state when temperature is raised over Tt. These features allow the direct delivery of those smart polymers in liquid state at low temperature (T<Tt) by specially designed catheters and subsequent switch in vivo to solid/hydrogel at body temperature (T>Tt).
INN 2. Conical endovascular catheter development for the deployment of the bioactive scaffold delivered as liquid and spontaneously switch in situ to an elastic hydrogel at body temperature.
During the third reporting period activities have focused on the translation of scientific results to the industrial setting in order to progress the technology to TRL 7.
In particular the following objectives were achieved:
i) Scale-up of rELP production and endotoxin removal process according to cGMP guidelines;
ii) Standardization of manufacturing of rELP-coated conic balloon according to the Medical Device Directive;
iii) Compiling the Design Dossier instrumental to the submission to a Notified Body;
iv) Start of GLP pre-clinical study to assess safety and efficacy on long-term;
The encouraging results obtained prompted the consortium to start an intense and highly focused road-show and results dissemination to raise additional funds to progress THEGRAIL technology to first-in-human trials after M60.

Project Results:
During the third reporting period activities have focused on the translation of scientific results to the industrial setting in order to progress the technology to TRL 7.
In particular the following objectives were achieved:
i) Scale-up of rELP production and endotoxin removal process according to cGMP guidelines. Within the framework of WP2, TBPNT and UVa have scale-up the production of rELP_09 to 100Lt fermenter achieving a 200 mg/L yield with a 0.26 EU/mg ELR.
ii) Standardization of manufacturing of rELP-coated conic balloon according to the Medical Device Directive. An industrial-scale manufacturing process for the coating of Nylon L25 semi-compliant balloon catheter with a 150µm of rELP_09. have benne developed, standardized and characterized
iii) Compiling the Design Dossier instrumental to the submission to a Notified Body.
iv) Completion of ex vivo tests and acute in vivo tests for material deployment and surgical procedure safety. The effective and targeted delivery of the rELP was proven.
v) Start of GLP pre-clinical study to assess safety and efficacy on long-term which will be be completed by the end of September. Preliminary results support the safety of the THEGRAIL technology with a survival rate >90%. Efficacy results are expected at the end of the pre-clinical study.
The encouraging results obtained prompted the consortium to start an intense and highly focused road-show and results dissemination to raise additional funds to progress THEGRAIL technology to first-in-human trials after M60.

Potential Impact:
The expected result of THEGRAIL project is a bioactive scaffold capable to regenerate the inner layer of blood vessels after endovascular treatment of the obstructed arteries in patients with atherosclerosis. This project will have an enormous social and economic impact in the field of CVD, diabetic disease, and the market for biomaterials. The results of the project represent a new approach to current therapeutic options for arteriosclerosis such as mechanical obstruction removal (angioplasty) or by pass. The THEGRAIL technology will allow to remove the atherosclerotic plaque and re-establish healthy physiological conditions by recruiting patient’s healthy cell on the injured site. In addition, the simple delivery system using endovascular techniques means that there will be no surgery required and therefore no complications from suturing, wound healing, anesthesia, infections etc will occur, thus shortening patients’ hospitalization and speeding up patient recovery after the intervention. The potential output product, could substitute the actual invasive and non-invasive technology for treating coronary, carotid and peripheral artery obstructive disease, granting long-term results, through its regenerative approach substituting the present mechanical dilatation and stenting.

List of Websites:
www.thegrail-project.eu

Related information

Contact

Davide De Lucrezia, (CEO)
Tel.: +39 041 50 93 865
Fax: +39 041 50 93 881
E-mail

Subjects

Life Sciences
Record Number: 191881 / Last updated on: 2016-11-21