TDP-43 for Neuro Disease

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Allosteric Modulators of TDP-43 for Treating Neurodegenerative Diseases Tech ID: UA20-044 Invention: This invention is a small molecule drug, nTRD22, that can be used to treat currently incurable neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and potentially even Alzheimer’s disease (AD) and Parkinson’s disease (PD). This molecule targets the N-terminal domain (NTD) of the DNA binding protein-43 (TDP-43) and causes allosteric modulation of the RRM of TDP-43, allowing for a new way to modulate RNA binding domains (RRM1 and RRM2) and target RNA-protein interactions in neurodegenerative diseases. Specifically, the nTRD22 compound, and its further derivatives, can be utilized to target the NTD of TDP-34 and disrupt the dimerization of TPD-43. Background: Neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis are among the top 10 most fatal incurable diseases. As the global population ages, the incidence of these diseases will continue to increase. Current drugs targeting these diseases can slow progression and reduce the severity of the disease’s symptoms, but they are not extremely effective at doing so, and none are able to cure the disease permanently. The present invention offers an alternative approach of targeting the NTD of TDP-43, which is a critical factor in several neurodegenerative diseases, involved in RNA metabolism. The present invention is a small molecule compound that offers a new way of modulating the RNA binding domains by causing allostermic modulation of the RRM of TDP-43.