Researchers Identify a New Therapeutic Target for C9orf72-Associated ALS

Researchers supported by The ALS Association announced that they had identified a new protein called SUPT4H1 that has potential to be used in therapy development for people whose ALS is caused by the C9orf72 gene. This research was published in the journal Science by Drs. Aaron Gitler at Stanford University in Stanford, California and Leonard Petrucelli at the Mayo Clinic in Jacksonville, Florida. Read on to learn more about this latest discovery.

Why SUPT4H1?

Drs. Gitler and Petrucelli targeted SUPT4H1 since it was shown that reducing its presence decreases the production of proteins containing long repeat expansions associated with another neurodegenerative disease, Huntington’s disease. However, reduction of SUPT4H1 did not affect expression of normal, non-expanded proteins.

Study Question

From the above observations, researchers decided to test whether reduction of SUPT4H1 would affect the expression of C9orf72 repeat expansions, which is the most common genetic variation associated with familial (inherited) ALS. The C9orf72 expansion, discovered with support from The ALS Association, leads to the production of both expanded “sense” and “antisense” RNA, along with proteins called dipeptide repeat proteins (DPRs) – all of which are potentially toxic to the cell.

Key Findings

Researchers found that reducing the amount of SUPT4H1 in yeast, fly and worm ALS models, reduced the production of toxic species produced by expanded C9orf72. The effect was specific in that SUPT4H1 reduction did not affect the normal C9orf72 gene. In worm and fly models, reduction also improved survival. Importantly, similar results were observed in cell derived from people living with ALS.


The exciting finding that reduction of a single protein, SUPT4H1, specifically reduces toxic gene products associated with C9orf72 long repeat expansions, gives researchers a new potential therapeutic target. The advantages to the approach of SUPT4H1 reduction are that it specifically targets only long repeat expansions and it targets all three potentially toxic gene entities (“sense” and “antisense” RNA and DPRs). Together, this could offer a powerful route to ALS therapies.

Next Steps

Researchers supported by The Association are developing specific inhibitors of SUPT41 and will then test them for safety and efficiency. These SUPT4H1 inhibitors represent a novel therapeutic approach to reduce toxicity associated with C9orf72 expansions.

Read more about SUPT4H1 in this press release.

4 thoughts on “Researchers Identify a New Therapeutic Target for C9orf72-Associated ALS”

  1. Adam,you are very brave,my son Larry also has been diagnosed in 2008. He is still fighting strong . He had a stem cell done inChina nothing evolved from that he is on cannibass oilwhichis helping some. He says the worst part of this disease is not being able to communicate. Stay strong and prayers for you and your family. I hope they can find a cure soon.


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