IIT Hyderabad's researchers identify a possible cure for neuro disease ALS

• Indian Institute of Technology (IIT) Hyderabad on Wednesday said its researchers have found a molecule 'AIM4' that shows promise in the treatment of a rare and debilitating neurodegenerative disease called 'Amyotrophic Lateral Sclerosis' (ALS).
• It occurs due to changes in specific genes, which may be triggered by factors such as smoking, exposure to toxins, metals and pesticides, a release from IIT Hyderabad said.
• The IIT Hyderabad research team discovered through computational studies AIM4 has specific binding site on this protein and binding energy calculations have shown that the bond between AIM4 and the mutant protein is energetically favourable, which makes it a promising drug for potential treatment of ALS

Indian Institute of Technology (IIT) Hyderabad on Wednesday said its researchers have found a molecule 'AIM4' that shows promise in the treatment of a rare and debilitating neurodegenerative disease called 'Amyotrophic Lateral Sclerosis' (ALS).

ALS, also known as 'Lou Gehrig's disease' 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, a release fromIITHyderabad said.

The results of this research, performed by a team led by faculty from the Department of Biotechnology, and Department of Chemistry, IIT Hyderabad, has recently been published in the peer-reviewedInternational Journal of Biological Macromolecules, it said.

According to the release, there are no drugs available at present to cure ALS and treatment options are limited to two drugs only for management of the condition.

Elaborating on this research, Associate Professor Basant Kumar Patel said,"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 liquid-liquid phase separation. This phase separation in turn causes the proteins to be deposited on nerve cells, resulting in neurodegeneration," he added.

In 2016, Patel and Prof Ganesan Prabushankar of Department of Chemistry 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, it said.

The IITH scientists then 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.

"We have shown that AIM4 prevents liquid-liquid phase separation of the modified protein, TDP-43-A315T. By this, AIM4 prevents aggregation of the protein andmay potentially prevent thedeposition on neurons,"Patel added.

The IIT Hyderabad research team discovered through computational studies AIM4 has specific binding site on this protein and binding energy calculations have shown that the bond between AIM4 and the mutant protein is energetically favourable, which makes it a promising drug for potential treatment of ALS, the release said.

The work by the IITH researchers shows that AIM4 is a promising molecule that must be studied further for development of drugs for ALS and perhaps even other neurodegenerative diseases, the release added.