MIAMI, Fla. (Ivanhoe Newswire) - Confined to a wheelchair
for life; that's the fate of many of the 12,000 people who suffer traumatic
spinal cord injuries in the United States every year. Now, a one of a kind trial could change the
face of spinal cord research forever.
"Before I even hit the ground I knew I was paralyzed," Marc
Bouniconti told Ivanhoe.
Marc Bouniconti's final football play paralyzed him from the
neck down.
"Next thing I know, I went from the best shape of my life to
fighting for my life in a split second," Bouniconti said.
Now, the son of an NFL hall of famer is fighting to walk
again and this could be the key. For the
first time the FDA has approved a trial to evaluate the safety of Schwann
cells, cells responsible for sending electrical signals throughout the nervous
system.
"The vision is that can we use these cells that normally
function in the peripheral nervous system to repair the central nervous
system," Dalton Dietrich, III, PhD, Scientific Director at the University of
Miami and Miller School of Medicine, told Ivanhoe.
In the trial, patients newly diagnosed with acute spinal
cord injury will be injected with their own Schwann cells. The idea is to help existing nerves in the
injured site grow.
Researchers saw about 70-percent improvement in function and
movement in paralyzed animals injected with Schwann cells.
"We'll never know, will we, until what we can accomplish
until we do this experiment in men," Dr. Dietrich said.
While he's not taking part in the trial, Marc hopes one day
it will help him.
"Science can do more than build a wheelchair, we can, we can
find a cure," Bouniconti concluded.
The trial will help develop future studies targeting
different types of injuries and therapeutic combinations. Dr. Dietrich said the study could take about
three to four years to complete.
RESEARCH SUMMARY
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)
INTERVIEW
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.
FOR MORE INFORMATION, PLEASE CONTACT:
Scott
Roy
Director of Communications
The Miami Project to Cure Paralysis
University of Miami Miller School of Medicine
305-243-8939
sroy@miami.edu
