The fight against ALS is made extremely challenging due to its largely unknown origin in most patients. This is the case for sporadic ALS, which accounts for up to 90% of all ALS cases, leaving this cohort of patients searching for answers. Our proposal aims to tackle one of the dominant theories surrounding sporadic ALS onset – a protein known as TDP-43. Significant research shows this protein appears to abnormally accumulate in motor neurons – the neurons that eventually die – in ALS patients. For this work, we aim to use small molecules of DNA called aptamers. These molecules can recognize and interact with some biological target thanks to a variety of forces between the aptamer and target. In our group, we can discover aptamers for different targets that are essentially like a lock and key – a unique DNA sequence being the key, and the target being the lock. By discovering unique sequences of DNA that can bind to the Prion-like domain (PrLD) of TDP-43, we hope to inhibit accumulation of TDP-43 and reduce TDP-43-associated toxicity.
