Addressing the technical, regulatory and ethical barriers to the safe and effective delivery of substances and cells directly into the central nervous system (brain or spinal cord) or cerebrospinal fluid (CSF).
HD research is entering an exciting phase, with new approaches such as huntingtin lowering strategies and cell therapies on the horizon. Many of these potential therapeutic strategies require direct delivery of the therapeutic agents directly into the brain or CSF. However, it is clear that direct delivery into the brain presents multiple challenges, many of which are common to all these approaches, Thus the mission of this new working group is to combine knowledge and expertise to develop solutions to these challenges.
- Identify and prioritise key challenge, which are likely to include: GMP production of cells or gene therapy products; differentiation protocols for cell products; safe, effective, and regulatory-compliant delivery of substances into the brain or CSF; the development of common protocols for clinical assessment; tracking of cells and substances following delivery; immunological reactions to the therapies; and trial design issues for interventional surgical studies.
- Determine working strategies, which may involve constituting several task and finish groups. These groups will identify specific barriers and will brainstorm ways forward. Part of this process may include review of the field, the production of recommendations, identification of specific research requirements, planning of specific research projects and identification of funding pathways.
- Develop effective common protocols for specific processes for delivery of substances (including cell and gene therapies) into the brain.
Since 2019 the Advanced Therapies Working group has been heavily involved in the evaluation of cell therapy strategies, a sub-set of therapies for HD. In order to enlarge the scope of this research, the group has established a partnership with an international network, Stem Cells for HD (https://www.sc4hd.org/) that addresses specific bottlenecks in current preclinical and clinical practice for the implementation of novel cell therapy strategies in Europe, Asia and North America. Considerations around cell production for clinical use, design of preclinical and clinical studies, biomarkers and follow-up after therapy, and regulatory requirements, and ethics are also in the scope of SC4HD. Both networks mutually benefit from the exchange of identified issues and knowledge and their synergy should accelerate the emergence of recommendations.
A reflection of this synergy is the prioritisation of issues and the identification of the bottleneck observed in the surgical delivery of cells to the brain. Thus, the Advanced Therapies Working Group has established a first task force on surgical delivery of cell therapies that feeds into the objectives of both networks. This task force was endorsed by the EHDN Think Tank in November 2020. A group of preclinical scientists and clinical academic neurosurgeons have had regular meetings to identify pertinent literature and establish the state-of-the art techniques and devices and problems encountered around cell delivery into the brain. A document is currently being written to inform the scientific community about current practice and challenges. A virtual meeting will be organized to discuss these findings across both networks and stakeholders (patient associations, regulatory bodies, pharma, etc…) with the scope of producing a position paper with recommendations on how to overcome these challenges.