Many of the more sophisticated forms of medicine, including gene therapies and immunotherapies, are challenging to deliver to the brain. At the very least there are far fewer practical options for delivery, and it is possible that none of that that exist fit a given desired use case. The blood-brain barrier stands in the way of intravenous injection as a path for most approaches, blocking passage of most cells and molecules from circulation to brain tissue. While direct injection into the brain or into reservoirs of cerebrospinal fluid can be achieved, they are sufficiently invasive and challenging to rule out commonplace use.
The brain is made up of many different cell types, and more sophisticated approaches will want specificity to regions or cell types. Small molecules can readily pass everywhere in the body, but are a poor tool if the goal is to engineer selective activity in a given cell type. That selectivity is readily achievable via any form of gene therapy in which expression is keyed to a promoter only active in the cell type of interest. But gene therapies with that capability are largely very hard to get into the brain, or have other characteristics that present hurdles. Forms of AAV viral vectors now exist that can pass the blood-brain barrier, but AAV is restricted in size of payload, and payload size is required for promoter-driven selectivity, ability to turn off the therapy at any point, and other add-ons.
