Protein in Cerebrospinal Fluid May Be Marker for ALS Therapy Success, Study Suggests

Scientists have found a potential protein biomarker in the cerebrospinal fluid of people carrying the most common mutation linked to amyotrophic lateral sclerosis (ALS) — suggesting that this protein may be useful to test the effects of drugs to treat this form of ALS in future clinical trials.

The study, “Poly(GP) proteins are a useful pharmacodynamic marker for-associated amyotrophic lateral sclerosis,” appeared in the journal Science Translational Medicine.

ALS is a devastating motor neuron disease for which there are still no effective treatments. Scientists have discovered that a mutation in a particular gene is the most common genetic defect leading to ALS, so they are investigating potential therapeutic strategies targeting this particular defect.

But the lack of measurable markers has hampered understanding of the effects of these investigational therapies. Now, scientists think they may have found a marker for the genetic defect which may be used to measure the potential for drugs to reduce ALS symptoms or even cure the disease.

Researchers first studied a group of ALS patients carrying the mutation in C9ORF72. They found that most of these patients had much higher levels of a protein, called poly(GP), in their cerebrospinal fluid and blood cells.

Of 134 individuals carrying the mutation, 83 already displayed ALS, while 27 were asymptomatic and 24 had other diseases. Moreover, they found that the levels of poly(GP) in the central nervous system of these individuals remained relatively constant over time. This is a good characteristic, suggesting its potential value as a marker for assessing the clinical outcomes of potential treatments.

Scientists used cells retrieved from individuals carrying the C9ORF72 mutation and a mouse model for ALS-caused by C9ORF72 to test one of these potential targeted therapeutics. The results showed that poly(GP) behaved as a marker for the changes induced by the therapy.

Overall, these results suggest that tracking poly(GP) proteins in the cerebrospinal fluid is a promising strategy to assess the effects of drugs targeting C9ORF72 mutation in symptomatic ALS patients, as well as in presymptomatic people who may benefit greatly from early therapeutic interventions.