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Turning Experimental Data Into Clinical Trials

Interview with Dr Jim Guest

James Guest is a professor of Neurosurgery at the Miami Project to Cure Paralysis at the University of Miami

We caught up with him to learn about his background and research into solving translational questions related to human clinical application in spinal cord injury.

Did you always want to be a scientist?

At some level, yes as I was a member of Science Clubs and interested in biology from an early age, but I didn’t know any scientists or doctors.

How did you progress into your current position?

I trained in neurosurgery at the University of British Columbia, and spent six months on the SCI unit. I was astounded by both the instantaneous change in people’s lives following injury, as well as the lack of restorative treatment.

I found there was a lot of progress being made in surgery, but there wasn’t anything to rebuild the damaged spinal cord. So I came to Miami for further training, completed my Ph.D. in cell transportation and finished my residency in Vancouver. Further training in the US led to me joining the faculty in Miami.

Image from Chang et al., 2021
Image from 'MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait', Chang et al., 2021

We have also been testing deep brain stimulation and have identified a target in the brain known as the cuneiform nucleus that can evoke walking.

Can you tell us simply about your area of research?

My research is quite broad, but one way to think about it is solving the problems of taking experimental animal data forward into testing in people with spinal cord injury.

Over the last 15 years I’ve been combining both clinical research and preclinical scientific experimental research. In the last 10 years we’ve been very interested in neuromodulation – use of electrical stimulation to elicit functional recovery – including to improve upper extremity function. We recently participated in the Up-Lift clinical trial conducted by the company Onward Medical. The relative simplicity to use some of these techniques in this area has really impressed us.

We have also been testing deep brain stimulation in a large animal model and have identified a target in the brain known as the cuneiform nucleus that can evoke walking even after spinal cord injury.

I am still involved in stem cell research. It was recently discovered that exosomes (small structures that carry cell products) have properties that don’t require stem cell transplantation. The benefit is that these are much easier to deliver to the spinal cord as they are infused intravenously and can cross the blood-brain barrier.

Key Terms

  • Stem cells: Cells with the ability to become other cells in the body.Some stem cells, such as multi-potent stem cells are limited in what they can become. Others, like pluripotent stem cells can become any cell in the body
  • Exosomes: small 'vesicles' or bubbles of cell membrane that bud off from the cell and transport cellular components, like growth-stimulating chemicals

Does length of time after injury affect the outcome of the research?

Time after injury is important – secondary Injury (increased inflammation and cell death) is real. If we can reduce secondary injury, we should be able to preserve tissue.

However, neuromodulation has changed the idea chronic injury was a limitation as you can have an effect decades after injury. An individual in our study had been injured for 36 years and responded to stimulation.

What is the current state of play in terms of research progress?

It has been accelerating tremendously over the years. Research programs take time to develop but we’re seeing multiple clinical trials for biologics (small molecules, antibodies, etc.) that hadn’t even been discovered two decades ago. Over the next 3 or 4 years we’ll discover if there’s a clinical effect of those drugs.

Chondroitinase (CHASE) – an enzyme that breaks down inhibitory tissue – has been a big source of encouragement as well, and something Spinal Research has been supportive of exploring for many years. Recently I’ve been involved in developing a new clinical trial for CHASE to be tested in people for the first time.

It is also unlikely that one single treatment will have a big effect, we need to address multiple targets. Combinatory treatments, such as rehabilitation coupled with stimulation and cell therapies, are very exciting.

Transcutaneous stimulation could be more widely available in the next two years.

Do we know when any meaningful therapies may be available?

With neuromodulation, what is needed now are robust clinical trials to determine who is likely to respond to the techniques and equipment we have now. Transcutaneous stimulation could be more widely available in the next two years.

In terms of biologics, those clinical trials are happening now. In 5 years we will have an answer as to whether those are beneficial.

Any specific plans for 2023?

We will be initiating studies of epidural stimulation for the recovery of autonomic function (involuntary bodily processes like blood pressure regulation)  in the next year, which I’m very excited about. Also hoping for a vacation at some point too!

Read Dr Guest's research

Pathophysiology, Classification and Comorbidities after Traumatic Spinal Cord Injury, 2022