In Search of a Biologic for Treating Back Pain

Two-time OREF grantee envisions injections to treat diskogenic pain
Samuel K. Cho, MD, a spine surgeon and research scientist on the faculty at Icahn School of Medicine at Mount Sinai in New York City, is leading an exploration of the molecular biology of notochordal cells. He is particularly interested in what chemical factors they may release or trigger that contribute to healthy disk cells. With the right combination of those factors, he hopes to create a biologic cocktail capable of managing or even eliminating the back pain that degenerating disks cause.


Samuel K. Cho, MD

Enlisting notochordal cells
In healthy young humans, notochordal cells are present in the intervertebral disk. Their role is to promote differentiation of other cells to bone, disk, or nerve tissues. Chemicals released by the notochordal cells orchestrate this work.

Both in utero and early in life, notochordal cells contribute to the highly gelatinous nature of disk nucleus by producing large quantities of proteoglycan and regulating the development of the disks' complex cellular structure.

However, all of that comes to a halt in early childhood, when human notochordal cells disappear.

By contrast, some animal species, such as pigs, retain notochordal cells through adulthood and do not experience disk degeneration.

"We want to better understand notochordal cells and learn what factors they release to the surrounding area that keep the disk cells healthy," said Dr. Cho.

Inhibiting pathways
Dr. Cho aimed to identify the growth factors and transcriptional regulators that are present as disk cells form and mature. With that knowledge, he saw the possibility of targeting and modulating specific genes associated with cell survival, differentiation, and matrix deposition.

Using human nerve and endothelial cells, the research team conducted a series of in vitro experiments: cell culture, inhibition, and rescue/blocking studies. They followed these with in vivo experiments that incorporated the results of the in vitro studies. Using a rat model, the team evaluated the effects of injectable biologic factors, both for impact on disk degeneration and for effectiveness in inhibiting nerve and vascular ingrowth.

"Learning what factors have an impact on disk degeneration could ultimately lead to medications that relieve patients' diskcogenic pain," said Dr. Cho.

Early encouragement
Participation in OREF-sponsored resident research symposia helped Dr. Cho cultivate his interest in research early in his career. The experience led him to apply for and secure a 2007 OREF/DePuy Resident Research Project Grant. That first OREF grant, he said, was "the impetus to continue my research efforts and continue my work in the lab and also in the clinic."

Six years later, Dr. Cho was awarded a 2013 OREF Young Investigator Grant to pursue this and other work toward new therapies to treat patients with disk degeneration. He described the grant as a launching pad for his work as a clinician scientist, treating patients and seeking biologic solutions for degenerative disk disease.

"The funding from OREF is providing invaluable preliminary data for long-term and bigger grants. With the results we obtain from the OREF-funded study, we'll potentially see ways in which we can treat patients with disk degeneration," said Dr. Cho.

Sharon Johnson is a contributing writer for OREF. She can be reached at communications@oref.org

© Orthopaedic Research and Education Foundation (OREF)

References:

  1. Heiney J: An examination and discussion of unintended consequences of being an employed physician. J Orthop Trauma 2013;Oct.
  2. Dyrda L: 25 Concepts for Young Orthopedic & Spine Surgeons to Build a Successful Practice. May 4, 2012. Becker's Spine Review http://www.beckersspine.com/spine/item/11832-25-key-concepts-for-youngorthopedic-spine-surgeons-to-build-a-successful-practice Accessed April 23, 2017.