With only looking through the article and being a 6502/NES programmer myself, you can't escape having to know 6502 and the NES hardware to write a NES game. This Lisp is cool and it will certainly smooth the process and is a good fit for an Adventure game and other parts of NES game development where you aren't counting cycles (like UI).
Good to know. Assuming it's true that 6502 asm is not too difficult to learn, co2 looks like it would be fun to work with on a simple game. Really neat project.
For me the challenge with the NES itself was getting a good tutorial and then with making a game, getting your art from your mind into the tiles and sprites and in your project. Your art 'pipeline'. Once that's established it becomes easier.
