To improve the transition from preclinical to clinical research in the field of gene therapy ZonMw developed the Programme Translational Gene Therapy Research. This programme is completely subsidized by the Dutch Health Ministry. The programme started in 2001 and ends in 2013.
Gene therapy is a way of treating disease by either replacing damaged or abnormal genes with normal ones or by providing new genetic instructions to help fight disease. The therapeutic gene must be packaged in such a way so that it is delivered only to the appropriate cells, and in such a way that it can enter the cell and incorporate into the host's genome.
Vehicles called vectors are most commonly used to deliver DNA to cells. Different types of vectors exist: viral vectors, non-viral vectors (liposomes, polymers) and physical “vectors” (electroporation). In viral vectors the genes that are necessary for replication and spreading of the virus are replaced by the therapeutical gene. This yields harmless viruses that are no longer able to cause disease. The viral vectors may be based on RNA-viruses (retrovirus, lentivirus) or DNA-viruses (adenovirus, adeno-associated virus (AAV) or herpesvirus). Retroviral vectors have been studied most so far. Of the DNA vectors, the adenovirus based vector has been studied most.
The first clinical gene therapy studies were performed with patients with a deficiency in the adenosinedeaminase (ADA) gene. Hemophilia and cystic fibrosis are other examples of monogenetic diseases for which gene therapy is in development. Gene therapy may also bring solutions for common diseases such as cancer and heart diseases.
The overall goal of the programme is to stimulate clinical gene therapy research following thorough preclinical translational research.
The programme has two main aims:
A. Preclinical translational research into the safety and effectivity of new approaches, aimed at continuation in clinical studies. Possibilities are the development of animal models and validation of new approaches in animal experiments. Production and quality control of batches of gene therapy vector used in clinical research will receive special attention. This may be carried out in cooperation with external parties.
B. Clinical research in phase I and/or phase II trials if justified by proper preclinical research, including the development of clinical protocols for these gene therapy studies
The programme aims to bridge the gap between basic research and patient care. It is therefore not directed at pure fundamental research. In addition, preclinical translational research (A) can only be supported when combined with clinical research (B).
Two types of projects
Type A+B Preclinical translational research combined with clinical research.
Type B Clinical research.
The total budget for the programme is 15.6 M€.
For the preclinical and pharmaceutical phase it is possible to obtain funding for a maximum of €125.000/year for a maximum of 4 years (post-doc and technical assistant of PhD student). In addition, €300.000 is available for the production and quality assessment of the gene therapy vector. The total sum of funding for the preclinical translational phase is €800.000 for 4 years. The clinical phase will, in principle, be funded for 2 years, and has a maximum of €550.000. For specific situations it is possible to extend the clinical phase with 1 year, without a change to the maximum budget.
Maximum budget for project type A+B:
Within this project type it is possible to combine both the preclinical phase and the pharmaceutical phase. Or just the pharmaceutical phase with the clinical phase.
Maximum time frame 7 years, maximum grant 1.4 M€. For pharmaceutical phase/clinical phase projects the maximum time frame is 4 years and the maximum grant is €1.075.000.
Maximum budget for project type B:
Maximum time frame of 3 years, maximum grant €550.000.
Application is open to researchers from Dutch institutes only. Foreign institutes or companies can participate in the projects.