M. Calancie, Ph. D. is a Professor of Neurological
Surgery at the University of Miami School of Medicine.
He specializes in Clinical Neurophysiology and
spinal cord injury.
works to understand the recovery of voluntary
movements or the development of involuntary movements
following spinal cord injury in humans. He and
his team use a variety of techniques to measure
aspects of the injured spinal cord as little as
12 hours after injury. Calancie and his colleagues
repeated evaluations of these persons over the
following weeks, months and years have revealed
previously unknown examples of 'plasticity' within
the adult human spinal cord.
lab is currently running a clinical trial to establish
the effects of weight-supported exercise on people
with incomplete spinal cord injuries. This study
will help determine if this therapeutic approach
can enhance the spinal cord's ability to improve
voluntary gait. Calancie's lab has also developed
several tests of spinal cord and nerve root function
which are now used routinely during spine surgery
and which help reduce the risk of post-operative
weakness in the patient.
links to this scientist's home page and other related
infomation please see our resources
Sergio Urias asked:
How long until we can start experimenting with
humans with spinal cord injuries?
experiments, like those described in my laboratory
on the program are looking at people with spinal
cord injuries. Others from my laboratory that
were not shown are helping us with some very clinically
relevant issues, like how to better diagnose and
understand the possible extent of recovery in
persons who have just had a spinal cord injury.
Information from these studies will help us better
understand the amount of positive effect (or negative
outcome, a possibility that we can't ignore) that
results from more invasive 'transplantation'-type
studies; I think it is these types of studies
to which your question refers.
question of when such trials directed at curing
SCI will occur is surrounded by controversy. Some
trials are already underway, including tests of
fetal spinal cord grafts (trial is completed),
cells (macrophages) which come from the same person
(autologous) and which are associated with the
immune system, electrical currents for promoting
spinal nerve elongation, and drugs (neuroprotective
agents) designed to reduce the amount of nerve
damage which occurs in the minutes and hours following
the initial spinal cord injury. With the exception
of the neuroprotective drug trials, all of these
are officially "safety" trials, and no firm conclusions
about effectiveness can be drawn (there is not
a good "control" group included in this type of
study). Even the large-scale trials of neuroprotective
drugs are notoriously controversial at the moment,
because many have shown no positive benefit, or
the benefits reported in some studies have since
been questioned as new findings from these studies
are dealing very intensively these days on understanding
how best to conduct clinical trials to maximize
the chance for success. This includes thorough
study of the therapy being tested, and thorough,
objective evaluation of the patients selected
for the trial both before and after treatment.
There is by no means agreement within the scientific
community of how much evidence is needed before
a trial should go ahead. Some therapies, like
stem cells, are discussed as being on the verge
of trials, but in fact very little is known about
the ultimate fate of the majority of these cells,
even in laboratory tests. For this reason alone,
some investigators would argue that clinical trials
of these cells for treating spinal cord injury
would be premature at this time.
Shannon Wilder asked:
Will bruised complete cords like mine be cured
before severed cords? Or will it just be everything
at once? And if the day does come around when
doctors are able to cure spinal cord injuries,
what type of waiting list will there be for thousands
of people like myself? Also, will people with
the funds be first and every body else be excluded
until who knows when? Thank for you time, c7 complete
often test severed cords in the laboratory because
any regeneration they then see will absolutely
positively have to come from cut nerves. But,
few real injuries occur this way. This level of
proof is needed scientifically, but most laboratories,
including my colleagues in Dr. Mary Bunge's laboratory
are also testing bruised cords as a "clinically
relevant model." In fact, in the trials currently
underway with strategies like fetal spinal cord
tissue and activated macrophages, the inclusion
criterion states that the cord must not be severed.
cannot say right now what the criteria will be
for any future trials and how the subjects will
be chosen. There is no "master waiting list" because
each experiment has unique criteria. Once a particular
treatment for long-term (or 'chronic') SCI has
been reported and repeated through independent
studies, I believe that the technology will quickly
become available in other treatment centers, such
that the prospects of having to wait for who knows
how long for a proven treatment are unlikely.
On the other hand, the Miami Project does maintain
a list of individuals who may be interested in
participating in ongoing clinical trials, which
may span a wide range of topics. For information
on what studies are currently underway, or to
obtain an "intake form" for our studies, please
or call (305) 243-7108.
Can the Central Pattern Generator help young MS
patients who have lost a great deal of their mobility?
is understood about the CPG is that it is made
up of a large group of nerve cells in the spinal
cord, and whose actions can give rise to regular,
smooth stepping-like movements in the legs. It
is likely that these movements are being continually
affected by the sensory consequences of previous
movements, as well as by continual 'commands'
from areas higher up in the spinal cord or brain.
MS can cause slowing down or complete failure
of conduction in some of these nerve fibers, which
would likely interfere with the ability of the
CPG to generate smooth movements. This doesn't
mean that movement is impossible, but it would
likely require a much greater amount of conscious
control efforts than what is typically considered
necessary for CPG-produced stepping movements.
Hi, my name is Suki. I have AVM and I am paralyzed
from the waist down. Even though I cannot move
my lower limbs significantly.
Would thinking about trying to tense/move the
limbs really help or is this a lost cause?
Sometimes I get spasms in the legs - some sort
of involuntary movement - what causes this?
I understand that the peripheral nerves can repair,
but if the nerves in spinal cord are damaged and
in future replaced, will these 'new' nerves still
know how to move previously paralyzed limbs?
I have come across the studies with rats. Some
researchers are optimistic, but others have reservations.
I gather that research into spine and nerve repair
have been going on for some time. Why has the
research been taking such a long time for some
sort of a cure? Christopher Reeves is positive
that there will be a cure in the foreseeable future.
Is he over-optimistic in your opinion? Can you
speculate about the types of spinal cord injuries
that can be cured?
5) There are many nerve fibers in the spinal cord
how do you know which ones are connected to which
parts of the body? If nerve regeneration is possible,
will the persons movement mimic that of a baby
developing in the previously paralysed limbs?
hard to answer your question without knowing a
little more about your history, like how long
have you had this spinal cord blood supply problem,
whether or not it was surgically treated, whether
or not you have involuntary movements (spasms)
or any sensation in your legs, etc. As a scientist,
I'm interested in your use of the term 'significantly':
does this mean that you have some volitional control
over your leg movements, but not enough to be
functional? Depending on your answers to my earlier
questions, this could mean that such efforts to
move your limbs might, in fact, be helpful.
for your second question, believe it or not, we
still don't know. There are probably a combination
of things that - together - contribute to the
movements in your legs known as spasticity.First,
I'm assuming that you've had some sort of spinal
cord injury; spasticity is known to be associated
with damage to certain parts of the brain or spinal
cord. As a result of that damage, it's thought
that some connections onto nerves in your spinal
cord that control leg muscles are lost. This opens
up portions of this nerve surface to allow new
connections to form. In the case of spasticity,
such connections are probably coming from sensory
receptors in your legs, skin and joints that already
go to your spinal cord, and now are having a stronger
effect. Different examples of the same type of
new growth in nerve fibers probably give rise
to chronic pain in some subjects, and may even
be the cause of abnormalities in blood pressure
control in persons with injury to higher parts
of the spinal cord.
are a number of treatments for spasticity, but
none of them are considered ideal for the majority
of subjects. Most involve taking differents forms
of drugs: valium and baclofen are two of the most
commonly prescribed. The method in which these
drugs are delivered is changing. Most persons
will take these drugs orally (by mouth, as a pill).
However, there are some persons with stronger
levels of spasticity who might need so much drug
that the side effects (when taken orally) are
unpleasant. Many of these persons seem to do very
well with an implanted pump which delivers small
but constant levels of these drugs directly to
those regions of the spinal cord that need them.
is my completely unproven idea that once we've
come up with strategies that improve leg function
following chronic spinal cord injury, some of
these 'secondary' effects like spasticity will
likely also benefit ... we'll see!
third question has not been completely answered
by scientists. Regenerated nerves that reach muscles
will "know how" to move them. But, when natural
recovery requires nerve growth over very long
distances, like the length of the arm, sometimes
nerves do not make it to the right muscles. When
a nerve mistakenly targets the wrong muscle, it
can still stimulate it; this may lead to "co-contractions,"
that is, different muscles working against each
other, actually making it more difficult to, say,
move your hand as you would wish to.
whole topic is called "guidance" by neuroscientists.
It a very hot topic, as basic research is done
to understand what messages nerves look for as
they are growing, and how to coax regenerating
nerves to the correct targets. There is some reason
to believe that nerve types that would normally
make contact with one another through normal development
might still 'remember' which contacts to make
following injury and regeneration, but such a
concept has not, to my knowledge, been tested
in the spinal cord.
get your 4th question virtually every day. We
understand that from the patient's perspective
scientific progress is painstakingly slow. What
many people forget is that only two decades ago,
spinal cord regeneration was believed by most
researchers to be unachievable. Since that time
the scope of SCI research has exploded, as SCI
researchers and their colleagues in related fields
have achieved important breakthroughs. They are
testing a number of animal models of injury, and
looking at a variety of treatments for SCI; this
includes different types of injuries as potential
targets for new clinical treatments. Still, experiments
with chronic injuries require months of post-injury
and post-grafting time in which to evaluate recovery.
Until these techniques are proven to work reliably,
most investigators feel that it would be unsafe
to test them clinically. That does not mean that
the positive outlook is over-optimistic, just
that the expectations need to meet the realities
of the challenge this injury poses. For further
discussion of this very topic, please see the
Project's web site under "Frequently Asked
answer to your last question is pretty much the
same as an earlier one about guiding growing nerve
fibers. As you suggest, relearning movements is
likely to be a very important part of any curative
therapy. That is why rehabilitation research like
the type my colleagues and I conduct is not just
about "care" but may well prove to be an important
part of "cure" research.
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