Periodic Reporting for period 4 - ARREST BLINDNESS (Advanced Regenerative and REStorative Therapies to combat corneal BLINDNESS)
Okres sprawozdawczy: 2020-01-01 do 2020-12-31
Approximately 30 million Europeans are currently blind or visually impaired, leading to a reduced quality of life and a tremendous increase in health care costs and lost productivity. Corneal blindness is the second largest cause of blindness globally after cataract, and millions remain unnecessarily blind due to problems of access to or lack of effective treatments. The current state-of-the art is characterized by an acute shortage of donor tissue, non-standardized use of donor cells, and a lack of targeted molecular therapies. The main goal of ARREST BLINDNESS is therefore to develop advanced technologies to regenerate or restore the cornea at the tissue, cell, and molecular levels, to maintain corneal transparency thereby preventing blindness. This will provide a direct benefit to millions globally, providing the means for vision restoration leading to improved quality of life and economic and social contributions to society as a whole from a large group of individuals.
The overall objectives of ARREST BLINDNESS are to replace the use of scarce donor tissue for corneal transplantation with cell-free tissue-engineered scaffolds. Further, cellular therapies are currently not standardized or approved for routine use in the most difficult cases of limbal stem cell deficiency or for endothelial dysfunction, and in the project these two cell-based therapies will be evaluated for first translation to patients, or for routine clinical use. Finally, new molecular and physical approaches to modify the neural and immune environment are being evaluated for the first time, as potential treatments for intractable corneal disease, where no suitable alternative therapies exist today.
The overall objectives of ARREST BLINDNESS are to replace the use of scarce donor tissue for corneal transplantation with cell-free tissue-engineered scaffolds. Further, cellular therapies are currently not standardized or approved for routine use in the most difficult cases of limbal stem cell deficiency or for endothelial dysfunction, and in the project these two cell-based therapies will be evaluated for first translation to patients, or for routine clinical use. Finally, new molecular and physical approaches to modify the neural and immune environment are being evaluated for the first time, as potential treatments for intractable corneal disease, where no suitable alternative therapies exist today.
By the end of the fourth reporting period, all 50 project deliverables have been submitted and 17 of the original 18 project milestones have been achieved. These measures indicate concrete progress made in all WPs and by all project partners.
A cornerstone of ARREST BLINDNESS was the four groundbreaking first-in-human clinical studies undertaken by the partners, each addressing a different corneal pathology leading to blindness, by using innovative, advanced new technologies promoting regeneration and restoration of tissue. By the end of the project, all clinical studies were completed. A novel GMP-compliant medical device made by an SME in The Netherlands, the Biocornea, has thus far had 100% success rate in 7 patients in Germany, as an emergency patch. A bioengineered collagen implant designed and manufactured by an SME in Sweden has been used to successfully treat advanced keratoconus in 20 subjects, using a newly-developed less-invasive surgical procedure providing fast healing and vision rehabilitation. A novel stem cell-based therapy has restored vision in the most difficult cases of stem cell deficiency in patients in Belgium, who would otherwise be blind. Finally, a German trial using a new combination therapy to regress blood vessels in the cornea in cases of high-risk transplantation has proven effective in patients, confirming the results obtained in preclinical models.
Besides the clinical studies, key innovations have been made in developing a new cultivated endothelial cell sheet based therapeutic procedure, that has been tested in several preclinical models and will be ready for translation into the first clinical studies in the near future. Finally, a novel neuroregenerative agent has been discovered and validated in several models of corneal injury and disease, with therapeutic effect exceeding today's best available treatment. Several of the technologies developed in the project have resulted in patent filings and the project has resulted in over 30 peer-reviewed publications, several popular scientific articles, numerous presentations at international meetings and conferences, a large following on scientific and professional media sites, and has led to new clinical trials and further EU-funded research projects among the project partners.
A cornerstone of ARREST BLINDNESS was the four groundbreaking first-in-human clinical studies undertaken by the partners, each addressing a different corneal pathology leading to blindness, by using innovative, advanced new technologies promoting regeneration and restoration of tissue. By the end of the project, all clinical studies were completed. A novel GMP-compliant medical device made by an SME in The Netherlands, the Biocornea, has thus far had 100% success rate in 7 patients in Germany, as an emergency patch. A bioengineered collagen implant designed and manufactured by an SME in Sweden has been used to successfully treat advanced keratoconus in 20 subjects, using a newly-developed less-invasive surgical procedure providing fast healing and vision rehabilitation. A novel stem cell-based therapy has restored vision in the most difficult cases of stem cell deficiency in patients in Belgium, who would otherwise be blind. Finally, a German trial using a new combination therapy to regress blood vessels in the cornea in cases of high-risk transplantation has proven effective in patients, confirming the results obtained in preclinical models.
Besides the clinical studies, key innovations have been made in developing a new cultivated endothelial cell sheet based therapeutic procedure, that has been tested in several preclinical models and will be ready for translation into the first clinical studies in the near future. Finally, a novel neuroregenerative agent has been discovered and validated in several models of corneal injury and disease, with therapeutic effect exceeding today's best available treatment. Several of the technologies developed in the project have resulted in patent filings and the project has resulted in over 30 peer-reviewed publications, several popular scientific articles, numerous presentations at international meetings and conferences, a large following on scientific and professional media sites, and has led to new clinical trials and further EU-funded research projects among the project partners.
A new porcine skin based collagen scaffold was developed to overcome deficiencies of previous attempts at tissue-engineering the bulk of the corneal tissue. This device has been tested clinically in patients outside the EU, using a newly developed intrastromal implantation procedure, which is minimally invasive compared to the standard more invasive techniques in use today. By the end of the Project it is expected that Clinical data with this device will enable larger-scale multi-center randomized studies to be conducted within the EU, to gather more Clinical data in support of a CE-mark application. Also within the Project, a fish scale collagen-based device, designed as a temporary emergency corneal patch, has been implanted in seven patients in a first-in-man trial, and by the end of the Project the results will indicate whether this technology can meet the great demand for an off-the-shelf solution to preserve vision in emergency corneal rupture cases, often seen in traumatic injury, for example in small remote clinics and in locations where other transplantation options or infrastructures are unavailable. Both these devices are defining the state-of the art in the field of corneal replacements, where no similar technologies exist. By the end of the project, these devices have the potential to alleviate the high demand and long waiting times for human donor corneas, which today keeps millions of cornea-blind people from being productive members of society.
While stem cell transplantation can treat corneal blindness, the procedure still carries high risks of tissue rejection and transplant failure. During the reporting period, a multi-center clinical trial of limbal stem cell transplantation using a GMP xenogenic-free process has applied new advanced stem cell imaging and real-time surgical imaging tools to optimize tissue harvesting and surgery, to improve patient outcomes. The outcomes of surgieries in all patients in the trial have been reported and final follow-up data is being analyzed. By the project end, these procedures have the potential to set a best-practice standard for this type of surgery.
A new non-invasive diagnostic imaging device for detecting corneal lymphatics has been developed for management of high risk vascularized corneas. The device based on optical coherence tomography, has been tested in preclinical models and in the first human subjects with positive results, with the device having received CE-mark and entering clinical studies. The studies have been completed and represent the first use of this technology in the setting of corneal transplantation. Combined with this innovation, new angio-regressive therapies targeting the immune response of the cornea have been tested with positive results. These innovations have the potential to prevent corneal graft failure. Each surviving corneal transplant saves €170,000 in long‐term health care costs, for a total savings of €6.8B if the current European transplantation rate of 2% could be doubled.
Finally, a new neuro-regenerative agent has been discovered for use in the cornea, and has shown promising results in models of corneal surgery and corneal disease. Combined with this new agent, a biomaterial-based slow release drug delivery technology was developed and validated in a relevant preclinical model, paving the way for further applications for drug development and first human clinical studies.
While stem cell transplantation can treat corneal blindness, the procedure still carries high risks of tissue rejection and transplant failure. During the reporting period, a multi-center clinical trial of limbal stem cell transplantation using a GMP xenogenic-free process has applied new advanced stem cell imaging and real-time surgical imaging tools to optimize tissue harvesting and surgery, to improve patient outcomes. The outcomes of surgieries in all patients in the trial have been reported and final follow-up data is being analyzed. By the project end, these procedures have the potential to set a best-practice standard for this type of surgery.
A new non-invasive diagnostic imaging device for detecting corneal lymphatics has been developed for management of high risk vascularized corneas. The device based on optical coherence tomography, has been tested in preclinical models and in the first human subjects with positive results, with the device having received CE-mark and entering clinical studies. The studies have been completed and represent the first use of this technology in the setting of corneal transplantation. Combined with this innovation, new angio-regressive therapies targeting the immune response of the cornea have been tested with positive results. These innovations have the potential to prevent corneal graft failure. Each surviving corneal transplant saves €170,000 in long‐term health care costs, for a total savings of €6.8B if the current European transplantation rate of 2% could be doubled.
Finally, a new neuro-regenerative agent has been discovered for use in the cornea, and has shown promising results in models of corneal surgery and corneal disease. Combined with this new agent, a biomaterial-based slow release drug delivery technology was developed and validated in a relevant preclinical model, paving the way for further applications for drug development and first human clinical studies.