HYDERABAD: INDIAN Institute of Technology, Hyderabad (IIT-H) researchers have found a molecule called ‘AIM4’ which can help in the treatment of a rare and debilitating neurodegenerative disease called ‘Amyotrophic Lateral Sclerosis’ (ALS), also known as ‘Lou Gehrig’s disease.’ ALS is a neurodegenerative disorder that severely affects voluntary movement of muscles and can lead to paralysis and death.
It occurs due to changes in specific genes, which may be triggered by factors such as smoking, exposure to toxins, metals and pesticides. Treatment can help in managing symptoms but this condition cannot be cured as there are no drugs for curing ALS. Research is going on throughout the world to find better drugs that can arrest this disorder and not m e re ly manag e t h e symptoms. “One of the causes of ALS is the alterations in the genes that code for a critical protein called TDP-43. The gene alteration modifies the protein, which results in its liquidliquid phase separation.
This phase separation, in turn, causes the proteins to be deposited on nerve cells, resulting in neurodegeneration,” explained Dr Basant Kumar Patel, Associate Professor, Department of Biotechnology, IIT-H, whose work was recently published in the Jour nal of Biological Macromolecules. In 2016, Dr Patel and Professor G Prabushankar found a small molecule called ‘AIM4,’ which seemed to be better than the other related molecules that have been studied all around the world, in its ability to inhibit abnormal aggregation of TDP-43 in vitro ALS disease model systems.
Armed with this knowledge, the IIT-Hyderabad scientists proceeded to analyse this molecule and study its action on TDP-43, to predict how it would potentially inhibit the deposition of the protein in nerve cells.