Praktyczne zagadnienia dotyczące podawania terapii genowej i komórkowej w padaczce skroniowej i innych zaburzeniach neurologicznych
Practical Considerations for Gene and Cell Therapy Delivery in Temporal Lobe Epilepsy and Other Neurological Disorders
W skrócie
Terapie genowe i komórkowe mogą być skutecznym sposobem leczenia padaczki i innych chorób neurologicznych, które dotychczas nie dają się wyleczyć. Jednak dostanie się tych leków do mózgu jest trudne ze względu na naturalne bariery w organizmie, a także wiele technicznych wyzwań związanych ze sposobem podania leku. W artykule porównano trzy główne sposoby podawania takich terapii - przez krew, przez płyn mózgowo-rdzeniowy lub bezpośrednio do mózgu - opisując zalety i wady każdej metody oraz to, jak wybrać najlepszy sposób dla konkretnego pacjenta.
Oryginalny abstract (angielski)
Biological cell and gene approaches have great potential to provide durable, disease-modifying therapies for, as yet, incurable neurological disorders. The central nervous system (CNS), unlike other organ systems, however, poses unique challenges for access for biological therapies. Access challenges include physical barriers such as the blood-brain barrier, technical barriers such as procedural considerations, and variability in response to biological therapies that are dependent on route of delivery. In this review, these challenges are discussed along with the practicalities of therapeutic access for biological therapies to the CNS by systemic intravenous (IV) delivery, intrathecal delivery, and direct intraparenchymal delivery in the context of epilepsy and with relevance to other neurological disorders. In the context of IV delivery, the practicalities of CNS target and off-target systemic effects are discussed. In the context of intrathecal delivery, the practicalities of procedural access, cerebrospinal fluid dynamics, and tissue penetrance are reviewed. Finally, in the context of direct intraparenchymal delivery, the technical aspects of therapy administration, local and systemic spread, and immune response are highlighted. Each delivery method provides a different balance of procedural, targeting, and inflammatory considerations, which may affect future therapeutic agent selection and trial design. This framework highlights that delivery-route selection should be individualized according to therapeutic modality, target anatomy, desired distribution, procedural risk, and clinical infrastructure.