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Regeneration of spinal cord

“Every step is a success”

09.04.2015
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Regeneration was long thought to be impossible for sufferers of spinal cord injuries. This might change in years to come.

Dr. Klaus Duffner | Germany

Professor Schwab, how far can our spinal cord regenerate after paraplegic injury?

Prof. Schwab: Up to 20 years ago it was believed that – unlike many other organs such as the skin, musculature or liver – there was no regenerative capacity whatsoever in the brain and spinal cord. Once destroyed, forever destroyed. At the time we wondered: why after cutting yourself with a bread knife is it possible to regenerate nerves in your finger, but not in your spinal cord? Despite initially good growth conditions we were not able to stimulate nerve cells from the spinal cord to grow sustainably.

 

Is this growth inhibition the case for all vertebrates?

Prof. Schwab: This is true for all higher vertebrates, i.e., frogs, reptiles, birds and mammals, not, however, fish and salamanders. Salamanders can regenerate and regain function in fibers cut off in the spinal cord or brain over long distances. They even renew whole legs. So these animals are of great interest to us. With this in mind we have scrutinized the processes after injuries in the mammalian spinal cord very closely, and we have indeed been able to observe very limited growth, but after about half a millimeter of nerve budding it was over. Why is this the case? At some point we realized: in central nerve tissue, mainly in myelin, there must be substances which inhibit growth.

 

So you set out in search of these substances…

Prof. Schwab: In cell culture we observed that extracted spinal cord strongly inhibited fiber growth. In contrast, extract from peripheral nerves was not inhibited at all. So there had to be an inhibitor in the CNS. And after a long search, we found it. This potent protein ensures that further growth is prevented in the spinal cord and “nothing else works”. We called it “Nogo A”. Then we developed an antibody to block a receptor of the protein using a lock & key mechanism. And guess what? When we applied the antibodies to a rat after a spinal cord injury, the nerve fibers did not cease to grow after half a millimeter, but were suddenly able to sprout for centimeters. That – a good 20 years ago – was the first proof that regeneration is possible in the spinal cord.

 

Do these new nerves tend to grow more on the periphery or more in the center of the cord?

Prof. Schwab: We very rarely find injuries to the spinal cord where the nerve pathways are completely severed. Ballistic wounds sometimes result in such a thing, but with “conventional” spinal cord injuries due to traffic or sports accidents we still tend to find thin bridges of tissue. It is these very bridges which use the regenerating fibers. But the time window for regeneration is limited owing to nerves retracting and scarring – in rats one week to ten days, in man probably about a month after an accident.

 

How far along are we from application in man?

Prof. Schwab: For the past few years we have been conducting clinical studies in cooperation with Novartis and a European network looking at people who have just been paraplegically injured. Phase I with 52 patients is complete, and a Phase II study is in the pipeline.

 

When will we see a drug?

Prof. Schwab: So far we have been in a highly experimental phase, and there is no therapy available yet. If we succeed clinically, it will still take a few more years for such a drug to be commercially available. We mustn’t forget: such an injury to the spinal cord is a catastrophic event. It is like hitting a computer with an enormous sledge hammer. You cannot simply patch it up. Many small steps are needed, but – just as for the patients themselves – even small steps are a success.

Dr. Klaus Duffner

Dr. Klaus Duffner | Germany

Scientific Journalist
Medizin & Wissen Freiburg

Interview by Dr. Klaus Duffner

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