Currently all prion diseases are considered fatal and incurable. I'll resolve yes if, by the end of 31 December 2045, there's a human being who was previously infected with prion disease (previously fatal and incurable) and has been cured of it, according to widespread medical consensus. Even if there are lingering side effects, I will resolve YES if the consensus is that death of said disease is no longer inevitable for that person. ("Inevitable" as in "the person is certain to die of said disease unless something else kills them first")
If a human has definitely been cured but the relevant medical intervention is hard or impossible to replicate, it's enough to resolve YES anyway. Something like the Berlin patient (but for a prion disease instead of HIV) would trigger a YES resolution.
If the medical intervention was intended for something else and accidentally cured the prion disease as a side effect, it's also enough to resolve YES.
If a human has been cured of a prion disease and it's unknown how that happened and what the cure was, this is still enough to resolve YES if there's a widespread medical consensus that this person really has been cured of said prion disease.
I may or may not freeze the market, resolve N/A, and/or consult the traders if a weird edge case arises and I'm unsure which was to resolve.
Related questions
How about exceeding the pre-treatment life expectancy by, say, 5 years as a sufficient criterium? From what I can see all four currently existing human prion diseases (CJD, vCJD, GSS, FFI) reliably kill in under 2 years from symptom onset
I doubt that for economic reasons, the potential cure would likely have to be extremely complex/expensive and the total number of patients is very low, compounded with problems with early detection
Also, unlike most other rare diseases the whole category is tiny, so there isn't even hope of easily reusing the research for other similar diseases