Many of the most potent disease-modifying treatments that are being considered for use in brain diseases are advanced therapeutic medical products (ATMPs, ie gene or cell therapies) or interfere with gene function, such as antisense oligonucleotides or interfering RNAs.
The reason for this is that they are often the best method for directly targeting disease mechanisms. However, getting these products safely and effectively into the brain is complex and poses several challenges. These challenges include multiple issues relating to surgical instrumentation, trial design, the selection of suitable and sensitive primary and secondary outcomes and compliance with regulatory regulations.
In addition, production of clinical-grade cell and gene medicinal products requires adherence to regulatory standards with extensive quality control of the protocols across different laboratories and production centres.
Addressing the challenges
Currently, there is no consensus on how best to address these challenges, so we formed two international consortia to address these issues for Huntington’s Disease (HD); Stem cells for Huntington’s Disease (SC4HD) and the Advanced Therapies Working group (ATWG), which is under the umbrella of the European Huntington’s Disease Network. The ATWG covers issues related to both cells and genes and the SC4HD picks up the additional cell-specific challenges.
Both groups comprise researchers and clinicians who are working to develop guidance and greater standardization for the HD field, in the hope that this will also provide a template for other neurodegenerative diseases. Both groups were established in 2018 and have held a series of international face-to-face meetings across Europe and North America (funded through Welsh Government, the European Huntington’s Disease Network, the California Institute of Regenerative Medicine and CHDI), in addition to regular online discussions.
Together we have published several papers that are starting to provide guidance for the field. This work is ongoing and in order to provide more depth of discussion to address the most difficult issues, we have formed several task forces. One example of a task force is the Neurosurgical Task force, which is holding a workshop in Venice in Autumn 2025, led by Professors Liam Gray, Anne Rosser in Cardiff and Romina Aron Badin in Paris, as part of the Neuroscience School of Advanced Studies series.