Final Report Summary - EPIXCHANGE (Innovative gene therapies for epilepsy treatment)
Aims of EPIXCHANGE. Epileptic seizures can originate in restricted areas of the brain (partial epilepsy) or involve all or most of the brain (generalized epilepsy). In about 30-40% of the patients, seizures cannot be blocked with current medications, and only a minority of cases are candidates for surgical treatment. Development of novel, more effective treatment strategies would therefore considerably lessen the societal burden of epilepsy. In this context, the main objective of the “Innovative gene therapies for epilepsy treatment” (EPIXCHANGE) project was to explore, provide the bases for clinical application and implement in the industrial arena new, advanced, unconventional strategies for the therapy of partial epilepsies as temporal lobe epilepsy (TLE). These strategies included the inoculation in the pathologic brain area of viral vectors (for the transfer of therapeutic genes) or of encapsulated cells (capable of supplementing therapeutic factors). In the future, these approaches could be used not only against epilepsy, but also for other neurological disorders and conditions, including neurodegenerative diseases.
The EPIXCHANGE consortium. The EPIXCHANGE project was funded by the European Commission, under the Marie Curie Industry-Academia Partnerships and Pathways (IAPP) action and officially started on the December 1, 2011. This project initially involved the University of Ferrara (Italy) as Coordinator, the University of Lund (Sweden) and the SME NsGene (Ballerup, Denmark), which is specialized in encapsulated cell biodelivery (ECB) therapeutic products. In its first year, EPIXCHANGE incorporated a new SME, BioViron (Lyon, France), specialized in the development and production of a particular type of vectors for gene therapy, called amplicons. The EPIXCHANGE consortium implemented a joint research programme to share and exploit the complementary competencies and technologies available at each participant site. By these means, EPIXCHANGE increased the mutual understanding and penetration of the different cultural settings and skills required for both the academic and the industrial sector, thus improving partners’ RTD capability and competitiveness.
Scientific results and their impact. EPIXCHANGE created several new tools for the cell and gene therapy of epilepsy. First, cell lines that effectively secrete inhibitory neurotransmitters capable to prevent or stop seizures; these cells have been encapsulated in a biodelivery system that can be positioned in the brain. Second, gene therapy vectors have been generated that can locally modulate the levels of factors implicated in the transformation of a normal brain in epileptic. These systems have been then tested in experimental models, encapsulated cell biodelivery system to inhibit seizures in chronic epilepsy, and gene therapy vectors to prevent epilepsy development in at-risk subjects. Based on animal studies, the most promising approach was encapsulation of cells producing and releasing a neurotrophic factor called BDNF: this strategy led to a dramatic reduction (greater that 70%) of spontaneous seizures and to the correction of epilepsy co-morbidities like anxiety, depression and cognitive impairment. Therefore, it is currently in a scale-up phase and will be eventually translated in a first-in-man clinical study.
Staff. The comparison between the complementary approaches available at each host organization has been ensured by the secondment of staff members. These researchers acquired knowledge of the techniques used in the different sectors and provided know-how for the transfer of these technologies. Seconded staff members became therefore able to conduct and manage research in any operational environment (industry or academia). Altogether, nine secondments took place in the EPIXCHANGE Consortium: three researcher were seconded from Ferrara (two to NsGene and one to BioViron); two were seconded from Lund (one to NsGene and one to BioViron); two from NsGene (one to Ferrara and one to Lund); two from BioViron (one to Ferrara and one to Lund). Moreover, three experienced researchers were recruited at Ferrara, Lund and NsGene, to bring top-level experience in techniques that are not present in the consortium. Assistance to researchers in connection to household, relocation, documents preparation and visa, where needed, were provided by the respective hosting organisations.
Organization of meetings and outreach activities. The partners have jointly organized annual open and free workshops, which were mandatory for all the researchers involved in the Network, but were also open to an external audience, allowing spread of information in the scientific community and attracting students interested in the EPIXCHANGE activities. During the first year of the project, the first and second Workshops have been organized in Lund (Sweden). The first was on the “Animal Model of Epilepsy” with a focus on: preclinical trials, design rules and regulations and the role of inflammation in experimental models of epilepsy. The second focused on the practicalities of “EC project management”, as a valuable complementary skill for the career of the researchers. Sixteen people participated to these Workshops. In the second year, the workshops on “Safety aspects related to the manufacture of gene and cell therapy products” and “Techniques for gene transfer in the CNS: viral vectors vs. engineered cells” took place in Ferrara. They focused on the latest advancements in gene and cell therapy for neurological diseases and on description and discussion of the rules that regulate the production and experimentation of advanced medicines like gene and cell therapy, both from the project and from distinguished invited speakers. The workshops were well attended (almost 200 registered individuals) and followed by local and national media. During the third year of the project, the annual workshop has been organized in Lund. It was entitled “Translational research in epilepsy” and focused on the rules that regulate the implementation of gene and cell therapies in first in man clinical studies. Forty people participated to this workshop. In the last year, the workshop on “Epilepsy research in the EU. State of the art and opportunities for the future” took place in Ferrara, and was organized in collaboration with an association of epilepsy patients. This was a unique event that gathered together the major EU-funded ongoing research projects specifically focused on epilepsy: six projects, accounting for a total EU investment of about 70 million euros. Moreover, major international funding agencies, both public and private, were invited at the workshop to present their portfolios of research-funding initiatives. The meeting was well attended (almost 150 registered individuals) and highly followed by local and national media.
Dissemination. Dissemination of project activities and results have been granted through the publication of a project website (www.epixchange.eu) the creation of a Facebook page, the distribution of press releases, the publication of articles in peer reviewed scientific journals, the creation of a leaflet to be distributed at national and international workshop, the publication of articles for lay newspapers, and the release of interviews for TVs. Moreover, the fellows seconded/recruited in the EPIXCHANGE consortium were active in communication activities directed to the general public. For examples, oral presentations, followed by laboratory activities were organised towards high school students in Lund and Ferrara, to present the project and create awareness on the importance of research to society.
Contact details. Michele Simonato, Project Coordinator, email: michele.simonato@unife.it
The EPIXCHANGE consortium. The EPIXCHANGE project was funded by the European Commission, under the Marie Curie Industry-Academia Partnerships and Pathways (IAPP) action and officially started on the December 1, 2011. This project initially involved the University of Ferrara (Italy) as Coordinator, the University of Lund (Sweden) and the SME NsGene (Ballerup, Denmark), which is specialized in encapsulated cell biodelivery (ECB) therapeutic products. In its first year, EPIXCHANGE incorporated a new SME, BioViron (Lyon, France), specialized in the development and production of a particular type of vectors for gene therapy, called amplicons. The EPIXCHANGE consortium implemented a joint research programme to share and exploit the complementary competencies and technologies available at each participant site. By these means, EPIXCHANGE increased the mutual understanding and penetration of the different cultural settings and skills required for both the academic and the industrial sector, thus improving partners’ RTD capability and competitiveness.
Scientific results and their impact. EPIXCHANGE created several new tools for the cell and gene therapy of epilepsy. First, cell lines that effectively secrete inhibitory neurotransmitters capable to prevent or stop seizures; these cells have been encapsulated in a biodelivery system that can be positioned in the brain. Second, gene therapy vectors have been generated that can locally modulate the levels of factors implicated in the transformation of a normal brain in epileptic. These systems have been then tested in experimental models, encapsulated cell biodelivery system to inhibit seizures in chronic epilepsy, and gene therapy vectors to prevent epilepsy development in at-risk subjects. Based on animal studies, the most promising approach was encapsulation of cells producing and releasing a neurotrophic factor called BDNF: this strategy led to a dramatic reduction (greater that 70%) of spontaneous seizures and to the correction of epilepsy co-morbidities like anxiety, depression and cognitive impairment. Therefore, it is currently in a scale-up phase and will be eventually translated in a first-in-man clinical study.
Staff. The comparison between the complementary approaches available at each host organization has been ensured by the secondment of staff members. These researchers acquired knowledge of the techniques used in the different sectors and provided know-how for the transfer of these technologies. Seconded staff members became therefore able to conduct and manage research in any operational environment (industry or academia). Altogether, nine secondments took place in the EPIXCHANGE Consortium: three researcher were seconded from Ferrara (two to NsGene and one to BioViron); two were seconded from Lund (one to NsGene and one to BioViron); two from NsGene (one to Ferrara and one to Lund); two from BioViron (one to Ferrara and one to Lund). Moreover, three experienced researchers were recruited at Ferrara, Lund and NsGene, to bring top-level experience in techniques that are not present in the consortium. Assistance to researchers in connection to household, relocation, documents preparation and visa, where needed, were provided by the respective hosting organisations.
Organization of meetings and outreach activities. The partners have jointly organized annual open and free workshops, which were mandatory for all the researchers involved in the Network, but were also open to an external audience, allowing spread of information in the scientific community and attracting students interested in the EPIXCHANGE activities. During the first year of the project, the first and second Workshops have been organized in Lund (Sweden). The first was on the “Animal Model of Epilepsy” with a focus on: preclinical trials, design rules and regulations and the role of inflammation in experimental models of epilepsy. The second focused on the practicalities of “EC project management”, as a valuable complementary skill for the career of the researchers. Sixteen people participated to these Workshops. In the second year, the workshops on “Safety aspects related to the manufacture of gene and cell therapy products” and “Techniques for gene transfer in the CNS: viral vectors vs. engineered cells” took place in Ferrara. They focused on the latest advancements in gene and cell therapy for neurological diseases and on description and discussion of the rules that regulate the production and experimentation of advanced medicines like gene and cell therapy, both from the project and from distinguished invited speakers. The workshops were well attended (almost 200 registered individuals) and followed by local and national media. During the third year of the project, the annual workshop has been organized in Lund. It was entitled “Translational research in epilepsy” and focused on the rules that regulate the implementation of gene and cell therapies in first in man clinical studies. Forty people participated to this workshop. In the last year, the workshop on “Epilepsy research in the EU. State of the art and opportunities for the future” took place in Ferrara, and was organized in collaboration with an association of epilepsy patients. This was a unique event that gathered together the major EU-funded ongoing research projects specifically focused on epilepsy: six projects, accounting for a total EU investment of about 70 million euros. Moreover, major international funding agencies, both public and private, were invited at the workshop to present their portfolios of research-funding initiatives. The meeting was well attended (almost 150 registered individuals) and highly followed by local and national media.
Dissemination. Dissemination of project activities and results have been granted through the publication of a project website (www.epixchange.eu) the creation of a Facebook page, the distribution of press releases, the publication of articles in peer reviewed scientific journals, the creation of a leaflet to be distributed at national and international workshop, the publication of articles for lay newspapers, and the release of interviews for TVs. Moreover, the fellows seconded/recruited in the EPIXCHANGE consortium were active in communication activities directed to the general public. For examples, oral presentations, followed by laboratory activities were organised towards high school students in Lund and Ferrara, to present the project and create awareness on the importance of research to society.
Contact details. Michele Simonato, Project Coordinator, email: michele.simonato@unife.it