This game should get native support for Nuzlockes. Yes I understand that it'd be a ton of work and that devs would need to focus on that rather than other things like regions. But so many people would benefit from this being a naturally supported thing. For example, look at Runescape they had ironman mode as an unofficial game mode that people would do by themselves. It got so popular it got implemented into the game. It brought tons of enjoyment and tons of new players enjoying that specific mode, it didn't matter that it was an MMO which encouraged training and stuff it made the game more diverse and better.
All you'd have to do is setup the nuzlocke rules, restrict trading , and a that'd be a wrap. So many people would want this. It'd probably be the most wanted feature behind a new region.