TDP-43 Inhibitors in Amyotrophic Lateral Sclerosis: An Application of Drug Repurposing Approach Using FDA-Approved Drugs

A motor neuron disease, Amyotrophic Lateral Sclerosis (ALS) causes the continuous decline in the functioning of neurons resulting in the symptoms like muscle cramps, weak muscles, difficulty in chewing and swallowing, muscle twitches, and unusual fatigue in limbs eventually resulting in paralysis. Being a Neurodegenerative Disorder (NDD), complete treatment is still not present. Studies provide some treatments and medications to slow down the progression of the disease and in the current era, based on the mechanisms of ALS several insillco studies are resulting in repurposed drugs that can be used for the treatment of the disease. These drugs can be used for further clinical research. In this paper, a list of FDA-approved drugs has been used to find a potential inhibitor for the treatment of ALS by inhibiting the mechanism of Transactive response DNA binding Protein (TDP-43). The entire work is based on the in-silico studies and drug repurposing approach. Abiraterone acetate resulted as the best binding drug with a binding affinity of -9. 1kcal/mol. Along with this drug, 9 more best-binding drugs were listed which can be repurposed for the inhibition of TDP-43 to slow down the progress of ALS.