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Researchers Stabilize ChABC to Degrade Scar Tissue and Promote Tissue Regeneration in SCI Patients

A team headed by Rutgers scientists has efficiently stabilized an enzyme that can degrade scar tissue caused by spinal cord injuries and stimulate regeneration of tissues with the use of artificial intelligence (AI) and robotics to make therapeutic proteins.

Researchers Stabilize ChABC to Degrade Scar Tissue and Promote Tissue Regeneration in SCI Patients.
Rutgers researchers are harnessing AI and robotics to deliver new hope for spinal cord injury patients, successfully stabilizing an enzyme able to degrade scar tissue resulting from spinal cord injuries and promote tissue regeneration. The study, recently published in Advanced Healthcare Materials, details the team’s ground-breaking stabilization of the enzyme Chondroitinase ABC, (ChABC.) Image Credit: Shutterstock.

The study explains the team’s radical stabilization of the enzyme Chondroitinase ABC (ChABC), which provides new hope for patients with spinal cord injuries. The study was recently published in Advanced Healthcare Materials.

This study represents one of the first times artificial intelligence and robotics have been used to formulate highly sensitive therapeutic proteins and extend their activity by such a large amount. It’s a major scientific achievement.

Adam Gormley, Study Principal Investigator and Assistant Professor, Biomedical Engineering, Rutgers School of Engineering, Rutgers University

Gormley stated that his research is also partly inspired by a personal association with spinal cord injury.

I’ll never forget being at the hospital and learning a close college friend would likely never walk again after being paralyzed from the waist down after a mountain biking accident. The therapy we are developing may someday help people such as my friend lessen the scar on their spinal cords and regain function. This is a great reason to wake up in the morning and fight to further the science and potential therapy.

Adam Gormley, Study Principal Investigator and Assistant Professor, Biomedical Engineering, Rutgers School of Engineering, Rutgers University

Shashank Kosuri, a doctoral student of biomedical engineering at Rutgers SOE and a lead author of the work stated that spinal cord injuries, or SCIs, can negatively affect the physical, psychological and socio-economic wellness of patients and their families. After an SCI, a secondary cascade of inflammation creates a thick scar tissue that can hinder or stop the regeneration of nervous tissue.

ChABC — the enzyme stabilized efficiently in the study — is known to reduce scar tissue molecules and stimulate tissue regeneration, but it is extremely unstable at 98.6 ° F (the normal human body temperature) and loses all activities in a few hours. Kosuri stated that this requires several costly infusions at much-increased doses to retain its therapeutic efficiency.

Synthetic copolymers are capable of wrapping around enzymes, like ChABC, and stabilizing them in hostile microenvironments. For enzyme stabilization, the team utilized an AI-driven methodology to synthesize and assess the capacity of multiple copolymers with liquid-handling robotics to stabilize ChABC and retain its activity even at 98.6 °F.

Although the scientists were able to detect many copolymers that functioned well, Kosuri noted that one combination of copolymer even persisted to maintain 30% of the enzyme for a maximum of one week, which is a hopeful result for patients who are seeking care for SCIs.

The study was financially supported by the National Institutes of Health, the National Science Foundation, and The New Jersey Commission on Spinal Cord research. Along with Gormley and Kosuri, the Rutgers research team also comprised SOE Professor Li Cai and Distinguished Professor Martin Yarmush, as well as many SOE-affiliated students. Faculty and students from Princeton University’s Department of Chemical and Biological Engineering also worked on this study.

Journal Reference:

Kosuri, S., et al. (2022) Machine-Assisted Discovery of Chondroitinase ABC Complexes toward Sustained Neural Regeneration. Advanced Healthcare Materials. doi.org/10.1002/adhm.202102101.

Source: https://www.rutgers.edu/

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