Methods for determining a rapid progression rate of amyotrophic lateral sclerosis (ALS) and restoring phagocytic function of microglia thereof using a NCK-associated protein 1 (NCKAP1) protein or an mRNA thereof

A method for determining a rapid progression rate of amyotrophic lateral sclerosis (ALS) in a test subject who has been diagnosed with ALS and restoring phagocytic function of microglia in the test subject with the rapid progression rate of the ALS, the method comprising:

• measuring a level of a NCK-associated protein 1 (NCKAP1) protein or an mRNA thereof in the microglia derived from a biological sample isolated from the test subject diagnosed with ALS;
• comparing the level of the NCKAP1 protein or the mRNA thereof in the microglia derived from the biological sample of the test subject with a level of the NCKAP1 protein or mRNA thereof in the microglia derived from the biological sample isolated from a healthy subject without ALS;
• determining whether the test subject has a rapid or slow progression rate based on the level of the NCKAP1 protein or the mRNA thereof compared to that of the healthy subject without ALS,
• wherein a lower level of the NCKAP1 protein or the mRNA thereof in the biological sample derived from the microglia of the test subject compared to that of the healthy subject is an indicator of the rapid progression rate,
• wherein a higher or equivalent level of the NCKAP 1 protein or the mRNA thereof in the microglia derived from the biological sample of the test subject compared to that of the healthy subject is an indicator of the slow progression rate;
• and
• wherein the progression rate is expressed as a change in amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) score (delta ALSFRS-R), the rapid progression rate has the delta ALSFRS-R score/month of greater than or equal to 1.5 and the slow progression rate has the delta ALSFRS-R score/month of less than 0.5, and
• administering the NCKAP1 NCKAP1 protein or the NCKAP1 protein-encoding gene to the test subject determined to have the rapid progression rate of the ALS and thereby restoring phagocytic function of the microglia in the test subject with the rapid progression rate of the ALS.