Frederick “Eric” Arnold, PhD, on Examining Genetic Variants for Polyadenylation

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The postdoctoral scholar at University of California – Irvine discussed research aiming to link genetic variants and neurodegeneration.

“We really want to do more detailed experiments to understand exactly what's happening when you lengthen this 3′-UTR. Is that affecting the trafficking of this RNA to different regions of the neuron... We think that eventually maybe we can try to design an array of antisense oligonucleotides to shift the polyadenylation site from the one that's associated with disease risk to the normal one, as a as a targeted therapy."

New research from University of California (UC) – Irvine is examining the TDP-43 protein, and how changes in alternative polyadenylation that are regulated by TDP-43 affect neuronal cells and amyotrophic lateral sclerosis (ALS). The team is aiming to find other associations and potential therapeutic targets for the disease apart from the known genetic causes, which only make up around 5-10% of ALS cases. Of these cases, the predominant associated genes are SOD1 and C9orf72.

The research, headed by Frederick “Eric” Arnold, PhD, postdoctoral scholar at UC Irvine, is also looking at genetic variants at the DNA level that are associated with changes in the polyadenylation site for tissues at the RNA level. Arnold discussed both the TDP-43 and the genetic variants research during a session at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, entitled "Translational research in ALS: Novel Biomarkers and Model Systems" held March 3-6, in Orlando. CGTLive® spoke with Arnold to learn more about the research, the findings so far, and how the work may lead to a better understanding of neurodegeneration.

Click here to view more coverage of the 2024 MDA Conference.

REFERENCES
1. Arnold F. Characterization of Alternative Polyadenylation Events in ALS Highlights New Disease Mechanisms and Novel Gene Therapy Targets. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Orlando, FL.
2. Amyotrophic Lateral Sclerosis (ALS): Causes/Inheritance. MDA website. https://www.mda.org/disease/amyotrophic-lateral-sclerosis/causes-inheritance#:~:text=About%205%2D10%25%20of%20ALS,specific%20region%20of%20a%20chromosome.
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