Natural enzyme re-engineered to tackle stroke and spinal cord damage

When nerve cells become damaged through a severe injury such as spinal cord damage or a stroke, the body’s natural defences go to work to limit the damage. This forms what is known as a glial scar, which protects against further injury but can impede long-term nerve repair.

Scientists have now redesigned an enzyme found in nature that selectively untangles some of the scarring in a way that promotes regrowth of the nerve cells, opening up new pathways in the development of treatments for these types of conditions.

The breakthrough comes from a team of engineers from the University of Toronto and the University of Michigan, but can be traced back a couple of decades to when scientists discovered an interesting function of an enzyme called chondroitinase ABC, which is produced in nature by bacteria. A glial scar consists of tightly woven cells and biochemicals that come together around the damaged nerve, and it was found that chondroitinase ABC could selectively degrade some of these building blocks in useful ways.

So much so that follow-up studies demonstrated how the enzyme could promote regrowth of nerve cells, with some experiments even demonstrating how it could lead injured animals to recover some of their lost functions. But scientists kept running into the same roadblock, with the enzyme proving too unstable for the job at hand.

The team sought the help of computer algorithms that enabled them to determine the correct building blocks to form a re-engineered form of chondroitinase ABC. Lab tests showed this version, with a total of 37 amino acid substitutions, to be more stable and active than the wild version.