‘1938’ a New Compound Boosts Nerve Regeneration; Protects Heart—Discovered in a New Research

By Sarnith Varun

May 25, 2023
spinal cord neuron cell
Nervous Tissue: Spinal Cord Motor Neuron

Research conducted by University College London (UCL) in collaboration with MRC Laboratory of Molecular Biology (MRCB), Cambridge, and AstraZeneca, a pharmaceutical company, discovered a compound named ‘1938’.1

1938 can not only regenerate nerves after injuries such as an accident, a fall, or sports, which can stretch, compress, crush, or cut nerves, and medical conditions, such as diabetes, and auto-immune diseases, it can also protect heart tissues from damages like in cases of heart attacks.

The compound serves several functions: it was found that 1938 increased neuron growth in nerve cells, and when tested on animal models, it reduced damage to the cardiac tissues after trauma, and it successfully regenerated lost motor in a nerve injury.

Currently, there is no medicine for nerve generation, though concrete research is needed to put compounds like; 1938 into practice, it is definitely a key find in developing advanced medicine for nerve generation and other cures. 

How does 1938 perform its functions?  

Phosphoinositide 3-kinase (PI3K), described as Molecular Machines by Dr. Roger Williams, a senior author of the study from the MRC Laboratory of Molecular Biology, is an enzyme that helps control cell growth, for example, it initiates wound healing. 

Dr. Roger explains Kinases are ‘molecular machines’ that are key to controlling the activities of our cells, and they are targets for a wide range of drugs. 

The study aimed to find activators of one of these molecular machines, with the goal of making the machine work better, eventually, they found that 1938 can directly activate a Kinase to achieve therapeutic benefits in protecting hearts from injury and stimulating neural regeneration in animal studies.

UCL and MRCMB tested thousands of molecules from the chemical compound library of AstraZeneca to create one that could activate the P13K signaling pathway, eventually, 1938 proved to be successful and its biological effects were tested.

Heart attacks cause damage to the heart cells, and once blood flow is restored, dead tissue areas form which causes problems later in life.

This is one such case where administering 1938 15 minutes after a heart attack could prove useful as it was found that 1938 provided substantial tissue protection in a preclinical model. 

Another experiment found that adding 1938 to lab-grown nerve cells significantly increased neuron growth, 

Nerve generation was achieved on the model of a rat with sciatic nerve injury, delivery of 1938 to the injured nerve resulting in an increased recovery in the hind leg muscle. 

The research group is now working on developing therapies for peripheral nerve damage in hands or arms caused by diabetes, but it can also result from injuries, infections, and exposure to toxins.

Further research on the effects of PI3K activators on the treatment of damage in the Central Nervous system such as spinal cord injury, stroke, or neurodegenerative disease., generally caused by an auto accident, sports injury, fall, ruptured brain aneurysm, lack of oxygen, gunshots, or an explosive blast, is also underway.

References

  1. Roger L. Williams et al., ‘A small-molecule PI3Kα activator for cardioprotection and neuroregeneration’, Nature, 24 May 2023, “Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development 1,2,3,4,5. This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation.”, https://www.nature.com/articles/s41586-023-05972-2[]
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