Watch the video here to learn more about the science behind ALS TDI's C9ORF72 discovery.


Scientists at the ALS Therapy Development Institute (ALS TDI) have discovered a new drug target for C9ORF72 ALS.

In a study that was recently published in Frontiers in Pharmacology, ALS TDI scientists present evidence implicating previously unexplored therapeutic target for C9ORF72-mediated ALS. The report titled, Type I PRMT inhibition protects against C9ORF72 arginine-rich dipeptide repeat toxicity, was authored by ALS TDI scientists, Alan Premasari, Anna Gill, and Fernando Vieira, M.D.

The study demonstrated that by inhibiting certain PRMTs (a class of enzymes that post-translationally modify proteins), scientists were able to protect against C9ORF72 arginine-rich dipeptide repeat toxicity. Specifically, they found that they could protect cells from C9ORF72 dipeptide repeat toxicity by inhibiting the PRMTs that cause asymmetric dimethylation, a specific molecular modification, to the amino acid, arginine. The results suggest that inhibition of asymmetric dimethylation could be protective against C9ORF72 ALS or also C9ORF72 frontotemporal dementia (FTD).

The recent study builds upon findings that ALS TDI scientists published in December of 2019, demonstrating that some arginine-rich dipeptide repeat proteins produced because of mutations in the C9orf72 gene are more toxic to neuronal cells than to non-neuronal cells.

“Finding new promising treatments for ALS will require new approaches. Our discovery of the potential involvement of Type I PRMTs in C9orf72-mediated ALS opens up entirely new and unexplored avenues for neurological drug discovery. I’m excited to advance this program and see what impact this could have on ALS,” said ALS TDI’s Chief Scientific Officer and study contributor, Fernando Vieira M.D.

This is significant because C9orf72 is the most common known mutation found in people with familial ALS, and has also been seen in some cases of sporadic ALS. Dr. Vieira noted that the discovery is most immediately relevant for patients who have the C9orf72 mutation, however, the findings may translate to other subtypes of ALS.

As next steps, ALS TDI scientists will explore this therapeutic target in other experimental model systems, both cell-based and in animals, and in human tissues in order to better understand its clinical relevance and ultimately identify or invent drugs that could be explored clinically.

To read the published study on Frontiers in Pharmacology, click here.