Ran proteins in sporadic amyotrophic lateral sclerosis

A method comprising:

• (i) detecting in a biological sample obtained from a subject at least one RAN protein;
• (ii) when at least one RAN protein is detected in (i), determining that the at least one RAN protein is not expressed from a C9orf72 or SCA36 locus of the subject;
• and
• (iii) identifying the subject has having or being at risk of developing sporadic ALS (sALS) based on the detecting of at least one RAN protein not expressed from a C9orf72 or SCA36 locus of the subject.

A method for diagnosing C9orf72 negative sporadic amyotrophic lateral sclerosis (C9− sALS), the method comprising:

• (i) detecting in a biological sample obtained from a subject at least one RAN protein;
• (ii) when at least one RAN protein is detected in (i), determining that the at least one RAN protein is not expressed from a C9orf72 locus of the subject;
• and
• (iii) diagnosing the subject as having C9− sALS based on the presence of the at least one RAN protein that was not expressed from the C9orf72 locus.

A method of monitoring a C9orf72 negative sporadic amyotrophic lateral sclerosis (C9− sALS) therapeutic regimen, the method comprising:

• (i) detecting in a second biological sample obtained from a subject that has been administered a therapeutic regimen for C9− sALS a level of one or more poly(GR), poly(GP), poly(GA), and/or poly(PR) repeat-associated non-ATG (RAN) protein(s);
• (ii) comparing the level of one or more RAN proteins detected in (i) to a level of the same RAN protein(s) in a first biological sample obtained from the subject prior to being administered the therapeutic regimen;
• and
• (iii) continuing to administer the therapeutic regimen for C9− sALS when the level of the one or more RAN protein(s) in the second biological sample is reduced compared to the level of the first biological sample,
• wherein the first biological sample and/or the second biological sample is blood, serum or cerebrospinal fluid (CSF).