Medical first! New hope for the paralyzed
BACKGROUND: Damage to any part of the spinal cord or nerves surrounding the spinal canal usually causes permanent changes in body functions below the site of injury. A traumatic spinal cord injury can come from traumatic blows to the spine that can dislocate, fracture, compress, or crush the vertebrae. Common causes of a spinal cord injury are falls, acts of violence, alcohol, motor vehicle accidents, and sport injuries. Additional damage can come from bleeding, inflammation, swelling, and fluid accumulation around the spinal cord that has gone untreated. A non-traumatic spinal cord injury is caused by cancer, arthritis, infections, inflammation, or disc degeneration of the spine. Researchers around the world have high hopes that advances in research will someday make the repair of spinal cord injuries possible. (Source: webmd.com)
TYPES/SIGNS: The ability to control the limbs after a spinal cord injury depends on two things: the place of the injury along the spinal cord and the severity. The lowest part of the spinal cord is referred to as the neurological level of the injury. The severity is classified as either complete or incomplete. A complete injury is when almost all sensory and ability to control movement are lost below the spinal cord injury. Incomplete injury is when some sensory or motor functions below the affected area are lost. Other names for a spinal cord injury is tetraplegia or quadriplegia, meaning arms, trunk, legs, hands, and pelvic organs are all affected by the injury. Paraplegia is a paralysis that affects part or all of the trunk, pelvic organs, and legs. Spinal cord injuries of any kind can result in loss of sensation, movement, bowels, changes in sexual function, difficulty breathing, exaggerated reflex activities, or pain caused by damage to the nerve fibers. (Source: webmd.com)
NEW TECHNOLOGY: Current treatment options include: medications, immobilization, surgery, and experimental treatments. There is no cure yet. Scientists have been trying to find new ways to stop cell death, promote nerve regeneration, and control inflammation. The FDA just approved a trial to evaluate the safety of Schwann cells. These cells are responsible for sending electrical signals throughout the nervous system. They are supportive, adult cells. They are not stem cells. Schwann cells have been transplanted into spinal cord injury sites for years. Researchers know that Schwann cells: produce growth factors, surround axons that lost insulation after injury, produce components of the extracellular matrix, spontaneously enter the spinal cord, are accessible by performing a biopsy of a small nerve in the leg, can be obtained in large numbers through a biopsy, and can be genetically engineered to produce more molecules. Participants in the FDA trial to evaluate the safety have to be in their “acute” phase (five days after the injury) and will be between 18 and 50 years old. Twenty-six to forty days after the injury, the patients will be injected with the Schwann cells into the site of injury. They will receive follow up for one year after surgery to evaluate medical, neurologic status, pain symptoms, and muscle spasticity. Scientists believe Schwann cells are one component of a multi-faceted cure. (Source: themiamiproject.org)
Dalton Dietrich, III, Ph.D., Scientific Director of UHealth’s Miami Project to Cure Paralysis, A Center of Excellence at the University of Miami and Miller School of Medicine, talks about transplanting Schwann cells to repair spinal cord injuries.
Can you explain to me what the Schwann cells are?
Dr. Dietrich: The Schwann cell is a cell that helps myelinate the nerves of the peripheral nervous system. Nerves running through your brain/spinal cord (central nervous system) and your peripheral nervous system, in your arms for example, are myelinated. Insulated just like the wires running in the walls at home actually. And when they become demyelinated they actually don’t function very well. So Schwann cells myelinate the peripheral nervous system and the vision is that we can use these cells that normally function in the peripheral nervous system to repair the central nervous system. The basis of the Schwann Cell Clinical Trial is to transplant a subject’s own cells into the injured spinal cord.
Can you give a little bit of detail of how they work in the spinal cord?
Dr. Dietrich: The Schwann cell we think will work in the spinal cord to repair function in a number of ways. The first is when you inject the cells into the lesion in the spinal cord, they are going to remyelinate, re-insulate, the demyelinated fibers. We now know from a number of sources that after spinal cord injury not all the axons are severed, many are just demyelinated and that demyelination leads to dysfunction. The Schwann cell is going to remyelinate those fibers and introduces action potentials running up and down the cord hopefully returning some function. Secondarily, the Schwann cell also releases growth promoting factors that make the axons that are near them actually grow like bulbs in a tree for example. Furthermore, the Schwann cell may be neuroprotective and prevent progressive injury from occurring. So that’s what’s exciting about Schwann cells. They can actually have multiple mechanisms in terms of repair.
Would it work the same way for somebody who has had an injury for a long time?
Dr. Dietrich: The FDA has approved our IND to first focus on sub-acute spinal cord injury subjects. That means the cells will have to be injected within 6 weeks of their injury. Your question is a good one regarding can we use this therapy in people living with a chronic spinal cord injury. And we think the answer to that is yes. In fact that’s the next IND we’re going to submit to the FDA to get approved where we’ll be starting the therapy months, years after injury.
If this is the key to finding a cure for paralysis, why did it take so long for the FDA to give you the go ahead to start?
Dr. Dietrich: It wasn’t an FDA problem. First, the scientists in The Miami Project have been working for over twenty five years to understand the biology of spinal cord injury. These are things you can’t pick up a text book and read about. There was no information on it. So a number of years ago, we started defining exactly what do we know about spinal cord injury, what do we not know about spinal cord injury, what are the key cellular responses that we want to protect against or promote in terms of regeneration., Once we understand that fairly well the big question became, okay, cell therapy, what type of cells do we want to use? Do you want a stem cell, a Schwann cell, an olfactory ensheathing glia cell, a mesenchymal stem cell, an embryonic stem cell, a fetal stem cell; it goes on and on and on. So none of that data are really known exactly what cell is going to be the best. The Miami Project about three years ago decided that we’re going to go forward with the transplantation of human autologous Schwann cells. Once we made that decision, we started having a discussion with the FDA about what we wanted to do. We had to provide data to convince them that it’s safe and there is some reason to do it, because it’s a very invasive procedure. So over the three year period of time we went back and forth doing our science, doing the modeling in terms of preclinical studies and learning for the first time how to process human Schwann cells through good manufacturing processes, GMP. That’s a big deal too, academic institutions don’t usually do that, it’s usually biotech and pharmaceutical companies that invest millions of dollars on these things. So yes we were very fortunate to actually move this forward within a three or four year period and the FDA was very helpful at every stage. They were tough, it’s the toughest thing that I have ever done as a scientist. I’ve written over three hundred papers. I’ve gotten millions of dollars in grants, but to get approved by the FDA to test an experimental therapy, what a hurdle that was. And until the twelfth hour I didn’t know if they were going to give us permission or not. So it was a very emotional time for us when the FDA said, Dr. Dietrich we have released your clinical hold and you can go forward. Right now we’re working to get IRB approval, just heard last week that we got IRB approval that allows us to do this therapy at the University of Miami. So we’re moving forward and I think actually relatively quickly.
So Phase I you’re going to recruit about eight people. How long after the spinal cord injury occurs?
Dr. Dietrich: As soon as they come in to the emergency room we’ll start pre-screening those individuals. Number one, they would have to have no feeling or movement below the injury site. Number two, these are going to be thoracic injuries only because we need to show first that we can put cells safely in thoracic injury versus a cervical injury, which of course is much more dangerous because unexpected problems could affect very critical functions. There’s certain main inclusion and exclusion criteria that we’ll check off, then we approach the person and inform them about the trial and request permission to take a small nerve biopsy from a sensory nerve in the leg. And from that small biopsy over three or four weeks we can generate millions of your own Schwann cells and at that time we’ll come back and talk to you again and will have a second consent process. The transplant will occur by 6 weeks after injury. Then we’re going to follow those subjects closely for one year to look at safety and then monitor less intensely for an additional 4 years.
What is the outcome of this, what would you like to see happen?
Dr. Dietrich: Well the first thing I would like to convince ourselves of as well as our colleagues, the FDA, and the scientific field internationally is that we can put Schwann cells into people safely, that’s the primary goal of this first trial. Secondarily, we’re following these subjects for many years so hopefully we’ll see some long term outcomes that are not predicted based on spontaneous recovery patterns. At the same time we’re doing this we’re also now preparing to talk to the FDA to go in to the chronic state that we talked about briefly already. But even more excitedly, we have these combination approaches. It’s not just the cell by itself, we can do drug therapies plus cell bridging strategies that we think will provide more recovery of function after spinal cord injury.
Right now there’s not much once you have a spinal cord injury, it’s rehab, rehab, rehab right?
Dr. Dietrich: Rehab, rehab, rehab – yes, but the rehab literature is actually pretty exciting right now with electrical stimulation, whole body vibration, etc. All these things that seem to be enhancing circuit plasticity and recovery of function. There’s a lot of things that we can do today to make a difference in people’s lives and The Miami Project has been doing that for the last several years so we’re excited about that. But now we want to take it to the next level in terms of continuing to do those things in addition to Schwann cells. This summer we started a boot camp for people living with spinal cord injury. My daughter comes home and I say where have you been? She goes, well I’ve been to boot camp, been exercising and all this training. So we said why don’t we have a boot camp for people living with spinal cord injury. They come in to The Miami Project, you see them on the first floor and they’re doing conditioning rehabilitation to get themselves in the best physical and mental state they can be. After spinal cord injury your muscles atrophy, you have a higher incidence of diabetes, cardiovascular disease, etc. We’re trying to target that today and use this boot camp rehabilitation to add on the future clinical trials targeting chronic injury.
This is going to be a safety trial first. What could be a bad outcome?
Dr. Dietrich: A potential bad outcome that we’re very sensitive to has to do with neuropathic pain. Do you know that the majority of people living with spinal cord injury today have abnormal sensation or neuropathic pain? We want to make sure we do not aggravate that. There’s also a risk of infection because it’s an invasive technique. We do not believe there’s any evidence for any tumors, that’s the other thing that cell therapists are concerned about especially when you look at embryonic stem cells. We don’t think that that’s going to be a problem regarding Schwann cells, but we’ve looked at that very closely. Another possible bad outcome could be increased spasticity.
How much improvement have you had in animal models?
Dr. Dietrich? They’re highly variable depending on the experiment. But I will tell you that some of the improvements we’ve seen we think are very clinically relevant. We have not cured paralysis if you want to just put that phrase out. We have significantly improved function in these animals when Schwann cells are given acutely or chronically so that’s what we’re looking for. We’ll never know what we can accomplish until we do this experiment in man. So that’s why we’re moving forward to do this Phase I safety trial.
Schwann cells are not being used in humans at all right, this will be the first time?
Dr. Dietrich: Schwann cells have been used in some very early studies targeting Multiple Sclerosis (MS). Remember we talked about re-myelination. Well MS is a demyelinating disorder. So some people have tried to use Schwann cells to remyelinate. Some people have tried Schwann cells in other countries with variable results. We don’t know exactly the condition of their Schwann cells when they injected them because they don’t really have a lot of information on how they processed the cells. So this will be the first FDA approved clinical trial using Schwann cells that we know are functional and have the ability to remyelinate central nervous system axons.
Do you consider this a game changer?
Dr. Dietrich: Oh it’s a game changer. This is like a big brick in the wall if you will. We’re trying to build this wall to overcome paralysis and it’s got hundreds of bricks. This is a really big brick, it’s a foundation of the wall and over the next several years we’ll continue to improve upon and build that wall until we have something that has a cure for paralysis written on it. That’s the vision.
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