Intrathecal gene therapy for neurologic disease in humans

The remarkable efficacy of recombinant adeno-associated virus gene therapy for rare genetic diseases, such as spinal muscular atrophy type 1 (SMA1),1 has raised expectations for similar benefits with other rare diseases. However, each disease has a unique mechanism and may require a specific distribution of transgene expression. In addition, the target cells for some diseases, such as the lower motor neurons for SMA1, may be easier to reach than deeper CNS structures with systemic intravenous (i.v.) AAV9 infusion.