Blair 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.

Calancie 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.

Calancie's 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.

4.17.01 Sergio Urias asked:
How long until we can start experimenting with humans with spinal cord injuries?

Calancie's response:
Some 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.

The 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 released.

Scientists 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.

4.17.01 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 since 4/29/99.

Calancie's response:
Scientists 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.

We 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 visit www.miamiproject.miami.edu or call (305) 243-7108.

4.17.01 Pam asked:
Can the Central Pattern Generator help young MS patients who have lost a great deal of their mobility?

Calancie's response:
What 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.

4.17.01 Suki asked:
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.

1) Would thinking about trying to tense/move the limbs really help or is this a lost cause?

2) Sometimes I get spasms in the legs - some sort of involuntary movement - what causes this?

3) 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?

4) 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?

Thanks, Suki

Calancie's response:
It's 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.

As 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.

There 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.

It 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!

Your 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.

This 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.

We 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 Miami Project's web site under "Frequently Asked Questions."

The 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.