When I was replacing peewee with PonyORM, I was evaluating a few options, including moving away from an ORM entirely and simply storing the metadata in indexed tables in memory. This would have also helped to solve a couple of minor annoying design issues (such as improper encapsulation of the actual content state into the application instance), but I ended up not doing this.
A big reason why is that there don’t actually seem to be any useful in-memory indexed table libraries for Python. Or many other languages.