A molecule found in blood and cerebrospinal fluid could serve as an indicator for the most common form of amyotrophic lateral sclerosis (ALS), offering a much needed tool to measure disease outcomes in clinical trials, a new study reports. No effective treatments currently exist for ALS (also known as Lou Gehrig's disease), a neurodegenerative disorder that rapidly progresses from symptoms of weakness and muscle atrophy to complete paralysis and death within 30 months of the initial diagnosis in almost half of all cases.

Despite more than 30 clinical trials since 1995, only one ALS treatment has been brought to market, and that compound, Riluzole, only extends survival by two to three months. Here, Tania Gendron and colleagues demonstrated that a genetic change associated with the most common form of ALS - known as C9ORF72 - also caused an abnormal protein called polyGP to accumulate in the cerebrospinal fluid (CSF) and blood cells of patients.

The researchers detected polyGP in CSF from 134 individuals with the C9ORF72 form of ALS, including from 83 ALS patients, 24 people with diseases other than ALS, and 27 asymptomatic carriers. Interestingly, polyGP was not found in CSF from 120 people lacking the C9ORF72 mutation, including 57 patients with a different form of ALS. What's more, when the scientists administered a therapy targeting the C9ORF72 mutation in mouse models of C9ORF72 ALS, they observed reduced polyGP levels in the animals' CSF.

The authors say that with further development, polyGP may prove to be a useful pharmacodynamic marker for therapeutic responses in clinical trials, especially for those patients who carry the mutation, but are not yet symptomatic.

Article: Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis, Tania F. Gendron et al., Science Translational Medicine, doi: 10.1126/scitranslmed.aai7866, published 29 March 2017.