A Q&A with neurological surgeon and spinal cord researcher James Guest, M.D., Ph.D.
James Guest, M.D., Ph.D., FACS has dedicated his career to the treatment of spinal cord injury and has made significant contributions to the field.
A Professor of Neurological Surgery at the Miller School of Medicine and the Miami Project to Cure Paralysis, he has authored more than 75 peer-reviewed publications, many of them focused on cellular therapy for spinal cord injury. He has also been actively involved in promoting innovative clinical trial design and the progress of essential data registries, including as an investigator for the North American Clinical Trials Network for the Treatment of Spinal Cord Injury.
Dr. Guest is a member of the Scientific Advisory Board for InVivo Therapeutics, which is developing the Neuro-Spinal ScaffoldTM for the treatment of acute spinal cord injury. We asked him about the current standard of care for spinal cord injury patients – and the potential for future improvements.
How do you define success in treating spinal cord injury?
Our concept of success has matured through experience and new knowledge.
We used to prioritize getting people to walk again. Now we also think about successes as helping people regain control of functions regulated by the autonomic nervous system, such as bowel, bladder and sexual function. We think about better cardiovascular control, and reducing the risk of complications such as metabolic syndrome, which is a cluster of conditions including high blood pressure and high blood sugar that together increase the risk of heart disease, type 2 diabetes and impaired brain function.
If we can improve regulation of the autonomic functions and reduce the risk of additional health complications, we can significantly increase quality of life. That’s a success.
Patient-reported outcomes are also very important to the success question. What does a person with the spinal cord injury think is success? Questionnaire responses from the spinal cord injury community have articulated their priorities. Recovery of hand function was the number one priority, then recovery of bowel, bladder and sexual function. Walking — was ranked third.
Is this type of success common?
We do see early successes – but we need to see them more widely, across more people.
Some of the variability in recovery is linked to the acute care. For example, the spinal cord should be completely decompressed so that the spinal fluid can move easily up and down the spine. But we don’t have a standard, either during or after the surgery, to evaluate how well we are decompressing the spine. If it’s not sufficiently decompressed, the opportunity for neurological recovery may be reduced.
Another issue is the quality and intensity of rehabilitation. Some patients go to state-of-the-art facilities after their acute care; others go to nursing homes with very minimal rehabilitation opportunities. That’s a large-scale problem as well.
Based on these examples, there is considerable room for improvement in the treatment of spinal cord injury.
How can InVivo’s Neuro-Spinal Scaffold potentially aid in the treatment of spinal cord injury?
The testing of the Neuro-Spinal Scaffold represents a major innovation in the potential treatment of spinal cord injuries and has been an important step in our field.
The idea with this scaffold is to treat severe injuries by opening up the damaged portion of the spinal cord and allowing the dead tissue to come out. That space is where the scaffold is inserted.
The highly porous scaffold leads to formation of a “neuropermissive matrix” that may improve the healing of the damaged cord. It is designed so that new cells settle in and grow during the repair process.
The testing of the Neuro-Spinal Scaffold represents a major innovation in the potential treatment of spinal cord injuries and has been a very important step in our field.
Is there potential to seed the scaffold with cells before inserting it into the patient?
When you put cells into the spinal cord without a scaffold a number of things can happen. Some cells might not survive, others migrate away, others may stay where they were implanted but fail to integrate into the spinal cord circuitry.
The introduction of cells along with a scaffold could have advantages if certain consequences occur. First, if the cells implanted with the matrix organized in a linear manner that traversed the injury site, nerve fiber regrowth could be improved.
Secondly, innovations of scaffolds could increase the likelihood of the cells’ survival. In this way, the scaffold could serve as a drug delivery tool. Even if the cells did not organize linearly, cells may attach to the scaffold and release various compounds into the damaged area of the spinal cord, which could promote healing. One application is to use the scaffold to release drugs that modify inflammation at the site of injury.
What is most exciting in terms of future treatment options with the scaffold?
The Neuro-Spinal Scaffold that InVivo has developed is a first-generation product. It came out of Bob Langer’s lab at MIT, and that’s a highly innovative group.
As the experience with the Neuro-Spinal Scaffold increases, I’m hopeful that there will be future iterations. There’s a lot of excellent research going on now to enhance the potential of biocompatible scaffolds. I see considerable potential for advancement as the scaffolds to combine therapeutics are developed.