Please check whether your newsletter issue template contains an editable region macro (check it here: CMS Desk -> Tools -> Newsletters -> Templates -> Edit). It often turns out that an editor deletes the following macro expression by accident: $$content:600:400$$. Once it is inserted back to your issue template, it is editable again.
Just a note: the “content” expression stands for a title of the editable region window – any codename (i.e. the name without spaces and special characters) can be used at its position.