Anna-Maria and Stephen Kellen Physician-Scientist Career Development Award Program- Part II
Research to Develop Non-Invasive Spine Fusion
We will post a series of blogs which will discuss specific research projects that are being conducted in part to the Anna-Maria and Stephen Kellen Physician-Scientist Development Award Program. In our second installment, Dr. Matthew E. Cunningham discusses his research on the development of non-invasive spine fusion.
Spine and scoliosis surgeons attempt to treat their patient’s conditions and ailments with non-operative options at first, including physical therapy, medicines taken orally (non-steroidal drugs among others), and specialized injections (epidural steroid injections, trigger points, and intra-articularly to the facets and sacro-iliac joints). But when clinical symptoms from end-stage arthritis, instability or spine deformity do not respond to non-operative measures, patients frequently need to undergo fusion of the spinal vertebral bones. Spine fusions can greatly improve or eliminate clinical pain symptoms, but the surgeries are relatively extensive and can have complication rates up to as high as 60% in some patient demographic populations. In an effort to minimize complications, hasten postoperative illness, and return patients to activities of daily living more quickly, I have been researching a method whereby a patient could obtain a solid spinal fusion after undergoing only an injection. Theoretically, this technique could eliminate postoperative procedure-related pain and requirement for hospitalization,. In addition, patients would not be at risk for intraoperative blood loss necessitating transfusion, wound infection, or other iatrogenic sequelae.
The spine is a repetitive series of hard bones (vertebrae) that support the structure of the spinal column, and soft-tissue discs between the vertebrae that allows spinal motion. There are also a collection of muscles that attach to the vertebral and other bones (such as the pelvis, ribs and shoulders) that support the spine in 3-dimensions. My research has concentrated on the disc tissue, in that it is a contained locale between 2 vertebral bones, which if converted from soft-tissue disc to bone, would allow the fusion of those 2 vertebral bones into a single one. The disc is comprised of 2 tissues: an inner jelly-like Nucleus Pulposus, and an outer ligament-like Annulus Fibrosus (AF). The disc is largely devoid of a blood supply, and gets its nutrition through diffusion from the peripheral AF capillaries, and those present in vertebrae juxtaposed proximally and distally to the disc. The NP tissue also appears to have an inherent homeostasis mechanism to prevent bone formation within the disc. Without a sufficient blood supply in the disc tissue, and with a tissue that apparently thwarts bone production, we expected that the research goal for developing a treatment to be injected into the NP space to make the disc turn into bone would be challenging. Delivery of genes (specific bits of DNA encoding proteins of interest) to alter the environment within the disc was chosen as a powerful method thorough which we might be able to achieve the goal. Initially, bone growth factors (bone morphogenetic proteins or BMPs) were utilized, and impressive amounts of bone were produced outside of the disc space that ultimately led to spine fusions in an animal model. Later study allowed us to discover a small molecule that made the NP tissue permissive to blood vessel ingrowth, a potentially big step forward towards making the disc more hospitable to bone growth.
The Kellen Physician-Scientist Center Development Award has enabled me to continue the quest towards injection-based non-invasive spine fusion. The grant support helps to fund a full time technician and PhD-level graduate student in my lab who complete the day-to-day work that has enabled us to make further discoveries, including delivery of 2 specific genes that render the NP cells permissive to generate calcium crystals within the NP disc tissue. Full description of the molecular mechanisms involved in this gene-mediated “reprogramming” of the NP cells is underway, and we are very excited about what this might mean for production of “real bone” within the disc space. I am very appreciative of the support provided by both Maria Kellen-French and HSS to provide the opportunity to continue by basic and translational research, and I remain confident that we will keep making progress towards, and eventually achieve the goal of percutaneous spine fusion.
Matthew E Cunningham MD PhD is an orthopedic surgeon at HSS, specializing in Pediatric and Adult, Spine and Scoliosis surgery. Dr. Cunningham’s interests include minimally invasive and open surgery for spine deformity and degenerative conditions. He currently is the Interim Chief of the Scoliosis Service, Director of the John Cobb Scoliosis Fellowship, Principal Investigator of the Molecular and Cellular Spine Research Laboratory at HSS, and acts as a reviewer for Clinical Orthopedics & Related Research, Hospital for Special Surgery Journal, Journal of Orthopedic Research, Arthritis Research & Therapy Journal, Scoliosis Journal, Biochemistry Journal, American Academy for Laboratory Animal Science Journal, and Journal of Biomechanics.