The present invention relates generally to methods for treating progressive neurodegenerative diseases, including their progressive forms. In particular, the present invention pertains to methods of treating or preventing progressive neurodegenerative diseases and its associated symptoms by administration of a combination of geranylgeranylacetone (teprenone) and ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine), or pharmaceutically acceptable salts thereof.