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The History of Spinal Cord Research


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In the past, paralyzed people could not be treated. Today, the first patients are taking their own steps again - thanks to spinal cord research. A chronicle of the most important events and insights.

 

Dark times

2500 BC: The first trace
The first written mention of paraplegia can be found in the Edwin Smith papyrus. It is the world's oldest medical record and describes the prevailing attitude over a long time: “An untreatable condition.”

500-150 BC: Definition of spinal cord injury
The Greek physician Hippocrates, regarded as the “father of medicine”, leaves behind the first medical description of chronic paraplegia and develops a stretching bench for therapy. Several centuries later, the Greek doctors Aretaeus and Galen define the different levels of paraplegia.

 

Beginning of research

1890: First experimental model
To better study spinal cord injury, the German pathologist Hans Schmaus established the first experimental model in rabbits.

1911: Improved model
The American neurologist Alfred Reginald Allen perfects the experimental model for paraplegia. It is essential for later research and is still in use today.

1928: A quiet hope
The Spanish neuroscientist Santiago Ramón y Cajal, one of the founding fathers of modern neuroscience, writes: “In adults, the nerves are fixed [...], nothing seems to regenerate.” But he is also the first to observe how damaged nerve cells (neurons) at least try to regenerate. However, without success.

 

Better care & first hope

1930: Rehabilitation
American physician Donald Munro is building a small department in Boston to treat spinal cord injuries. He introduces the concept of rehabilitation - the only treatment for functional recovery to date.

1945: Better care
With Ludwig Guttmann, a British neurologist born in Germany, expectancy and quality of life of spinal cord injuries increases. He develops treatment methods and is considered by many to be the founders of the modern rehabilitation of paraplegics.

1968: First functional recovery in animals
The American neuro-anesthesiologist Maurice Albin and the neurosurgeon Robert White cools the spinal cord tissue in the animal model by using hypothermia. This improves functional recovery. The therapeutic approach has currently been taken up again and is being tested in a clinical study.

 

The dogma “paraplegia is incurable” is overturned

1981: Axons can regenerate
Doctor Albert Aguayo and neuroscientist Sam David, both from Canada, write history. They show that axons (extensions of a nerve cell) can also regenerate in the central nervous system - if the environment is right. In rats, they transplant part of the sciatic nerve (leg nerve) into the spinal cord. Axons of the central nervous system grow into this graft. A sensation!

 

Explore new approaches

1990: First spinal cord injury recovery
The Swiss neuroscientists Lisa Schnell and Martin Schwab succeed to promote the growth of axons in a rat spinal cord injury model. With an antibody, they can lift the “inhibition” and achieve a recovery. This work has great influence on the research field and acts as a magnet for scientists and sponsors.

1990: The glial scar
For the first time, the American neuroscientist Jerry Silver describes how the glial scar - the scar over the injury site - prevents nerves from growing out again.

1991: Hope for chronic paraplegia
The American neuroscientist John Houlé shows that axons continue to regenerate long after a spinal cord injury. The proof that regeneration is possible - even for patients with chronic injuries.

1995: First Hydrogel
Swiss physician and neuroscientist Patrick Aebischer manufactures the first biomaterial. He develops a hydrogel into which neurons can grow.

1998: First Electrostimulation
The Slovenian doctor and neuroscientist Milan Dimitrijevic shows with his work in Austria that an electrical stimulation of the spinal cord can trigger walking in paralyzed people.

2001: Receptor of inhibition
American physician and neuroscientist Stephen Strittmatter discovers a Nogo receptor that inhibits the growth of axons. A clinical study based on these findings is currently in preparation.

 

New findings

2002: Scar softening
British neuroscientists James Fawcett and Stephen McMahon show that the glial scar (see 1990) can be softened by using a special enzyme (chondroitinase ABC).

2004: Plasticity
Martin Schwab describes plasticity in paraplegia. This means that nerve endings form new links. Pre-existing circuits are used, which are still intact after the injury.

2005: Stem cells
For the first time stem cells are used in spinal cord injury. The American neuroscientist Hans Keirstead demonstrates in an experiment with rats that human stem cells can rebuild the missing myelin sheath and thus restore functions.

2007: Immune paralysis
The German neurologist and neuroscientist Jan Schwab finds out that paraplegia affects the immune system allowing for infections which render recovery difficult.

2008: Molecular brake
Neuroscientist Zhigang He of Harvard Medical School is able to strengthen the nerve-gowning ability to regenerate by turning off a molecular brake for axon regeneration (PTEN).

 

Moving to humans

2010: First study on embryonic stem cell therapy
A clinical trial is testing the effects of embryonic stem cells on subacute paraplegia. In 2015, this approach will be revisited in a new study.

2010: Release the brake
Based on the findings of 2008, Zhigang He succeeds for the first time in regenerating the corticospinal axons. These are essential for motor control.

2012: Neurotechnology
French neuroscientist Grégoire Courtine presents a technology that allows rats to walk despite severe paraplegia. He uses an electrochemical neuroprosthesis and a robot-assisted rehabilitation training.

2015: Pressure matters
Neurosurgeon Marios Papadopoulos and neuroscientist Samira Saadoun from St George's University Hospital, London, are studying the pressure in the spinal cord of recently injured patients. Optimal pressure conditions should reduce the consequences of paraplegia.

2016: News for the scar
The American neuroscientist Michael Sofroniew shows that the “demonized” glial scar is in fact important for the regeneration of damaged neurons. Without astrocytes, which are significantly involved in the formation of the scar, the axonal re-sprouting is much more difficult.

2018: Regeneration, breathing and first attempt
Grégoire Courtine succeeds in restoring walking function in three incompletely injured patients. He uses an electrostimulation developed from his 2012’s project. In the same year, Jerry Silver can restore breathing in chronic model of paraplegia. 

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