Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - BrainMatTrain (Development of Biomaterial-based Delivery Systems for Parkinson’s disease - an Integrated Pan-European Approach)

Teaser

1.1 The problem being addressedParkinson’s disease (PD) is a chronic neurodegenerative disorder characterised by the progressive loss of dopamine producing neurons in a particular part of the brain resulting in various motor and non-motor symptoms. The loss of these cells is...

Summary

1.1 The problem being addressed
Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterised by the progressive loss of dopamine producing neurons in a particular part of the brain resulting in various motor and non-motor symptoms. The loss of these cells is caused by chronic neuro-inflammation and this results in a feed forward cycle promoting further inflammation and neurodegeneration within the brain which characterizes the pathophysiology of PD. Current treatments for PD are symptomatic pharmacotherapies that neither address the underlying disease pathogenesis nor prevent, slow or halt the chronic, progressive neurodegeneration.
The BrainMatTrain research programme focuses on a comprehensive understanding of Parkinson’s disease and aims to develop novel biomaterial-based scaffolds, which facilitate functional regeneration in the central nervous system (CNS). Our project aims to target both the inflammation and neurodegenerative phases of the underlying pathology by using collagen reservoir scaffolds incorporating drugs and cells that are targeting these phases of the disease.
BrainMatTrain is fully supported by four research institutions, two hospitals and three small and medium sized enterprises (SMEs). The latter are ideally placed to exploit the final results for commercial gain.
1.2 Overall Objectives
The main scientific and technology objectives of the research programme are to:
• Design functionalised collagen-based scaffolds for the delivery of therapeutic moieties
• Investigate efficacy of functionalised scaffolds in in vitro models of Parkinson’s disease
• Conduct preclinical studies on the delivery of functionalised biomaterials in in vivo models of Parkinson’s disease
• Scale up collagen scaffolds
• Develop a device for delivery of functionalised scaffolds
• Provide world-class research and complementary training to a new generation of highly skilled researchers
• Receive training in integrating the gender dimension in decision-making, research and innovation content to improve the scientific quality and societal relevance of the produced knowledge, technology and innovation
1.3 Importance for society
Parkinson’s disease is the second most common neurodegenerative disease affecting more than 10 million people worldwide. Many neurodegenerative diseases are incurable due to the progressive degeneration and/or death of neuron cells. As research advances, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic progress that could ameliorate many diseases simultaneously.
Therefore, this project supports the EU objectives on research on neurodegenerative disease diagnosis and treatment as the European Parliament has repeatedly emphasized the importance of addressing the challenges of neurodegenerative disease in research as well as in social and health policies.

Work performed

2. Work performed and main results
Various collagen hydrogels have been successfully designed, optimised and fabricated which resulted in final products that proved to be non-toxic and highly stable both in vitro and in vivo. These hydrogels have the capacity to encapsulate cells or drugs that can be delivered at the site.
Secondly, a delivery system targeting neuroprotection and neuroinflammation was successfully developed. The addition of a neurotrophic factor (GDNF) to the hydrogel showed a significant reduction of cellular degeneration within the brain model, whereas the addition of the cytokine interleukin 10 (IL-10) revealed a reduced inflammation in the host.
Also, new in vitro next generation PD model systems are currently being developed within the project. A robust protocol has been designed for the re-programming of adult human fibroblasts from patients with PD into dopaminergic neurons.
Another model of PD in progress is the lab-on-a-chip (LOC) model. Different fabrication techniques have been explored for the so-called bio-printing (3D printing) in various hydrogels. A new printer is being developed that enables 3D printing of cells in liquid collagen as well as in hydrogels.
To characterise the in vivo responses of implanted biomaterials, a robust animal model of pure neuroinflammation was successfully achieved. The degree of the pathophysiological effects can now also be measured before and after implantation of different hydrogel variations by analysing the mRNA expression patterns of certain inflammatory markers, the changes on the protein patterns (proteomics), and in vivo characterization via positron emission tomography (PET).
Further, our industry partners are developing protocols and strategies for the scale-up of the biomaterial for later commercialisation. For the device design to deliver the multimodal system into the brain, physical stress conditions of the hydrogels during injection to enhance the material stability on a larger scale have been successfully conducted.
Additionally, to ensure that sufficient quantities of mesenchymal stromal cells (MSCs) will be available for use in the clinic, transformative technologies that deliver highly purified MSCs, called ORBCEL-CTM, have been successfully developed. These cells are currently modified and optimized to be used in a closed automated cell expansion system to scale-up the manufacture process.

Final results

3. Progress beyond the state of the art
Exploitation of the research results is expected. The primary output is a commercially viable hydrogel system that can be delivered by a unique device capable of delivering encapsulated therapeutic agents and cells. Within the lifetime of the project, steps involved in the research (risk assessment, primary regulatory studies, laboratory non-GLP) and preclinical studies (Product class, and patenting stages) will be completed. Preclinical testing of scaled-up devices in in vivo models will be completed during the project’s timeframe, which will enable rapid translation and commercialisation after the lifetime of the project.
Additionally, this European Training Network will educate and train 15 Early Stage Researchers (ESRs) in functionalised biomaterials, materials science, molecular biology, stem cell biology, in vitro model systems, in vivo neuroimaging, preclinical models and prototype design.
BrainMatTrain aims to deliver graduates that are immediately employable across sectors. The researchers will be provided with knowledge of the interrelated, multidisciplinary fields necessary to fully engage in the tools of tissue engineering and regenerative medicine. They will further undertake cross-disciplinary research projects so that, despite different backgrounds, they will understand each other’s ‘language’ and can jointly and successfully execute the proposed research program.
Further, the BrainMatTrain’s performed outreach activities are promoting a conducive environment to engage with the general public providing an understanding about the role of science and encouraging young people to take Science, Technology, Engineering, and Mathematics (STEM) subjects.
Also, the fellows supported primary and secondary level school science by hands-on workshops and delivery of teaching materials (neurodegenerative diseases and biomaterials concepts) with direct relevance to the curriculum and inspired the next generation of scientists by highlighting potential career opportunities in science.

Website & more info

More info: http://www.brainmattrain.eu.