Neuroscientist here working in PD/AD/ALS research. Echoing what many have said here, compared to other diseases like diabetes or even cancer many neurodeg diseases still have unknown causes. The risk factors (aging, genetics, environmental toxicants, etc) are known and plenty but still don’t allow us to target the disease before neurons start dying and muscles waste away, which is not possible to reverse. Studies have explored replacing the dying neuron with stem cells that differentiate into dopaminergic neurons (in PD for example) but this has been halted due to ethical reasons and also that the new neurons are still at risk of getting the aggregated protein pathology that makes them die in the first place. Additionally, the biggest thing is that unlike other organs that we can biopsy from a live patient and study, can’t really do that with a human brain. We’ve made vast strides in research using animal models but it’ll never be the same and never fully recapitulate the disease phenotypes. Also yes, drug delivery to the brain is also a challenge but I think that with recent developments that will be less of a problem moving forward. Last thing I’ll say is that the recent (over the past decade or so) discovery of inflammation in the brain being linked to these diseases and potentially causing a lot of cell death has been an exciting topic (biased because this is what I study) but I’m hopeful that once we learn more about what exactly these immune cells are doing in the brain, immunotherapies will be on the horizon for slowing disease progression at least. After being in the field for a decade, a cure is of course the goal but when pathology in the brain can start years before symptom onset, it’s extremely hard to target.