Wings for LIFE magazine - Edition No. 8

WINGS FOR

We have one mission: to make spinal cord injuries curable.

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EDITION NO. 8

www.wingsforlife.com

SPINAL CORD RESEARCH FOUNDATION

We

Love This Run!

The Wings for Life World Run moves the World PEOPLE A Dive That Changed Everything

RESEARCH The Potential of the Vagus Nerve

INTERVIEW Yale-Professor Stephen Strittmatter

FOREWORD

IMPRINT Wings for Life International Spinal Cord Research Foundation Fürstenallee 4, 5020 Salzburg, Austria Phone: +43-662-6582-4244 Email: office@wingsforlife.com Company Registration: FN 251592p Legal Form: Private non-profit foundation Register Court: Landesgericht Salzburg (Jurisdiction) Chief Executive Officer: Anita Gerhardter Wings for Life United Kingdom Seven Dials Warehouse 42-56 Earlham Street London WC2H 9LA Great Britain UK Registered Charity No: 1138804 Wings for Life USA Spinal Cord Research Foundation Inc. 1630 Stewart Street, Santa Monica, 90404, CA

Dear friends and supporters, Everyone experiences living with a spinal cord injury differently.

For Gabor, it means requiring constant help after spending a day at the seaside. For Raphael, it is pondering the memory of his last trampoline jump. For Julia, it means dealing with her own uncertainty as to whether she can be a good mum to her little daughter despite being confined to a wheelchair. Every spinal cord injury has its own personal history. We would like to share some of these with you in this issue.

501 c3 Charity Contributors: Markus Boettinger, Vieri Failli, Wolfgang Illek, Verena May Editors: Marco Gröbner, Stefanie Schwarz Head of Commercial and Publishing Management: Stefan Ebner Creative Director: Dominik Uhl Photo Editor: Matti Wulfes Design: Andreea Parvu Lithography: Clemens Ragotzky

However, we are also eager to share why we harbour so much hope. A review of the history of spinal cord research illustrates the progress so far and the speed at which new discoveries are currently being made (see page 54).

Furthermore, we examine an exciting study in Texas. Researchers are creating new nerve connections with nothing more than a small chip in the patient’s neck (see page 44).

Coverphoto: Marcelo Maragni; Photo: Alexandra Fazan

Translation: Manfred Thurner Sub-Editor: Jonathan B. James Producer: Friedrich Indich, Walter Sadaba, Sabine Wessig

You make all this possible. Thank you for donating to us, attending our events, and helping us make a difference.

Editor & Executive Director: Andreas Kornhofer Printer: Offset 5020 Druckerei & Verlag Ges.m.b.H., Bayernstraße 27, A-5072 Siezenheim

We hope you enjoy reading this latest issue of our magazine.

Your Wings for Life team

Acknowledgement: We would like to express our gratitude to Red Bull Media House for producing this magazine free of charge and Offset 5020 for donating the paper.

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CONTENT ISSUE No 8

10 PEOPLE

RESEARCH

16 How Do You Tell Your

Child He Is Paralysed?

The touching story of a special family

28 Did You Know…

…what a functional hand is?

30 Gabor’s Last Dive

How a head-first dive into the water completely changed the life of a young man

16

50 The Baby Adventure

Julia recounts what it’s like to

give birth with a spinal cord injury

66 Column

Thoughts after visiting

a rehab facility

24

20 Scientific Meeting

The elite of spinal cord

researchers meet

22 Research Compact Global advances in science

24 Mission: Research

Yale professor Stephen

Strittmatter talks about his clinical trial

STANDARDS 3 Foreword, Imprint

50

34 44 FUNDRAISING

Photos: Alexandra Fazan, Samo Vidic, Predrag Vuckovic, Karlo Ramos, Mark Teo

44 The Vagus Nerve –

A Jack of All Trades Researchers in Texas create

6 Snapshots

Our most beautiful moments

and greatest events

new nerve connections by stimulating the 12th cranial nerve

 54 The History of Spinal Cord Research From papyrus to the

present day

60 The Axon Whisperer Neurologist Zhigang He

has managed to regrow nerve fibres

34 We Love This Run!

The Wings for Life World Run

moves the world

64 Favourite Pieces

Our new collection is here

6

SNAPSHOT

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Independent Photo: Ann Ziegler

We all held our breath when we saw David Mzee at the Wings for Life World Run in Zug. The spinal cord injury patient from Switzerland participated in an electrostimulation study funded by us. He demonstrated his progress when he walked across the starting line independently. A huge step for research – and a milestone for David. ... LIFE | 7

SNAPSHOT

Ready, set, go for the clay pigeons!

The traditional “Clay Day� always requires sure instincts and accuracy from all participants. Celebrity hosts Christian Horner and David Coulthard joined the guests in shooting at clay pigeons and raising money for Wings for Life. The relaxed afternoon event yielded the equivalent of 161,000 Pounds.

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Photo: Wings for Life

SNAPSHOT

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Walk of heroes Photo: Richie Hopson

Richard, Simon, and Stu on the coast of southern England. The three friends hiked 110 miles for us in less than four days! The trek was totally worth the blisters on their feet: their fundraising campaign yielded ÂŁ10,000 for spinal cord research. ... LIFE | 11

SNAPSHOT

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Big hitters on the green

Foto: Photo:Marcelo Ian Witlen Maragni

This photo shows Anthony Netto at the “Wings for Life Golf Classics�. The spinal cord injury patient from South Africa has developed a wheelchair that allows golfers with spinal cord injuries to enjoy the sport. He was one of many special guests on our golf tour with stops in Chicago, Scottsdale, and Miami. Auctions and sponsors raised more than 730,000 Dollar for research on the green.

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SNAPSHOT

And action!

Actor Gregor Bloéb “acted out” in front of our photo wall. This year’s “Gipfeltreffen” in Austria was not only a thoroughly enjoyable affair, but also a huge success in terms of donations: 383,777 Euros for spinal cord research.

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Photo: Jürgen Skarwan

SPINAL CORD INJURY

Photos: Alexandra Fazan, private

How Do You Tell Your Child That He is Paralysed?

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Raphael is lying in his hospital bed and has no idea that he has suffered a spinal cord injury. His mother s gaze lingers on his immobile legs. “Every now and then my heart begins to race and I think to myself: this here - his paralysis - will never go away

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1

2

3

W

e meet 15-year-old Raphael and his parents, Annette and Wolfgang, in a café.

Raphael doesn’t order anything and starts talking about the fateful day in the last summer holidays.“On August 15, I decided to visit a nearby lake. I arrived ten minutes before my friends and figured I’d kill some time on the trampoline.” The sun was out in full force, scorching the ground. Raphael jumped, sweated, and let off steam. He propelled himself upwards with forceful leg movements, again and again. But his body couldn’t take the strain, his circulation was weakened. “I felt dizzy and hit the middle of the trampoline neck first, unchecked.” Raphael’s body rebounded a little, then remained motionless. “I remember it very well. All I could do was move my eyes.”

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1. Raphael is allowed to sit up for the first time after intensive care 2. Raphael has got used to life in a wheelchair. He is, however, not willing to accept his fate just yet 3. The family stick together and offer the schoolboy as much support as they can

After a few minutes, a holidaymaker became aware of the injured boy. “Every touch felt like a burning knife being rammed into my body.”

A short while later, Annette got a phone call.

“Someone told me that my son had fallen down and couldn’t move his legs. I’m a mother of two boys, so I’m used to all sorts of trouble. I didn’t think it was anything dramatic at the time…” Annette arrived at the scene of the accident shortly thereafter. She knelt next to her son to calm him down. Raphael was lifted into a rescue helicopter by emergency physicians.

“MUM, I KNOW…” Annette feared for her child at the hospital. Her husband was on a foreign assignment with the Austrian military at the time. Her older son, Philipp, was spending several weeks in Ireland.

Raphael was examined closely and had to undergo emergency surgery. Then he was put into an induced coma. Two days later, Wolfgang returned home and had to absorb what had happened.

An attentive pastor soon realised that the parents hadn’t received sufficient information regarding their son’s injury. “Then the head physician filled us in. He explained that Raphael’s vertebrae were displaced by the fall and that the spinal cord was injured at the level of the fifth

“We were at his side all the time. All we could do was try and calm him down” Raphael´s dad Wolfgang

cervical vertebra. He told us that our son was now quadriplegic, which meant that he could not walk, that he could not move his arms and fingers.” It was a horrific diagnosis. Raphael spent two weeks in an induced coma, which was followed by a long recovery phase. He couldn’t talk. “We were at his side all the time. All we could do was try and calm him down,” Wolfgang explains.

The worries and fears came when the couple were alone in the evenings. “We were afraid of the future. But the worst aspect for me was that my son didn’t even know that he was paralysed,” Annette remembers. “They didn’t have to,” Raphael interjects. “I knew right from the start was happening with me, kind of. When my condition improved a little and I slowly regained my voice, I talked to a nurse about it.”

When Annette visited her son in the ICU that day, he welcomed her with the words: “Mum, I know.” It was a huge relief for the mother of two.

“I couldn’t have looked him in the eye and explained something like that…”

AN ARDUOUS PATH Raphael started his rehab after six weeks. None of the functions returned - his body remained paralysed. But he began to familiarise himself with the wheelchair, underwent various therapies, and built up muscles again. He was allowed to return home after eight months of rehab. Raphael seems serene. His family gives him enormous support. “I get up at 2am every night to turn and catheterise him,” Wolfgang explains. “And I help him whenever he struggles with drying himself or dressing,” Annette adds.

Their greatest wish is an independent life for their son.

Raphael wants to be a teacher. He’s very determined. “I’m actually coping quite well,” he says matter-of-factly. “But if there really was a cure, I’d love to play volleyball with my friends again.” He’d like to be as carefree as he was before the accident. At the lake with the trampoline …

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KNOWLEDGE

Scientific Meeting Personal exchange is paramount. Our annual scientific meeting provides the brightest minds in spinal cord research with a platform to present and discuss their latest findings

101

SCIENTISTS

@ IM

R AKE B N O AAR

Moving

OPENING SPEECH

@GCOURTINE

# C OM

on stage

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MONG

OAL

Photos: Andreas Schaad, Marco Grรถbner

Bright minds

Photo: R. Schedl

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SCIENCE

Research

Compact ➤ HOW MICROGLIA WORK Professor Steve Lacroix and his colleagues at the University of Laval, Canada, have discovered something truly amazing: microglia cells protect neurons and oligodendrocyte cells

SPINAL CORD INJURY PATIENTS MOVE ARMS AND HANDS Dr Natasha van Zyl is a neurosurgeon based in Melbourne. She and her team combined tendon and nerve transfers in 13 recently injured patients.

The result: increased strength and improved fine motor skills. Two years after surgery, some patients were able to eat, drink, write, or use their respective wheelchairs independently.

The next step is a more extensive study.

Lancet, July 2019

promoting the tissue-protecting function of microglia with a growth factor (M-CSF), thus improving recovery after a spinal cord injury.

Nature Communications, February 2019

♦ DESTRUCTION AIDS GROWTH Particular factors destroy the structure of the cytoskeleton after a spinal cord injury. Professor Frank Bradke’s team of researchers in Bonn recently discovered that this process can also promote growth. They proved, for the very first time, that influencing a single protein family (AC proteins) is sufficient to stimulate regeneration.

Neuron, September 2019

♦ NANOTECHNOLOGY RESCUES SPINAL CORD TISSUE Scientists led by Dr Lonnie Shea of Michigan University have developed special particles – so-called nanoparticles – that are absorbed by immune cells.

As a result, fewer immune cells reach the injury site in the spinal cord. This reduces the inflammatory reaction, which, in turn, means that less tissue is destroyed.

Thus, the nerve tissue can recover more effectively.

PNAS, July 2019

➤ CELLS DIGEST THEMSELVES Autophagy literally means “selfconsuming”. It is a natural process in which the cell removes superfluous or non-functional components and subsequently recycles them. Researchers from Miami and Louisville have discovered that this process is very 22 | WINGS FOR ...

from collapsing after an injury.

Conversely, experiments have demonstrated that the removal of microglia increases tissue damage and worsens motor functions. Moreover, the researchers have succeeded in

important for myelinisation, meaning the formation of an insulating layer around nerve fibres. Further research will reveal whether and how autophagy can be harnessed to repair the nerve insulation layer after a spinal cord injury.

Glia, June 2019

The importance of respiratory exercises It is extremely important to undergo respiratory muscle training after a spinal cord injury in order to avoid life-threatening pneumonia. A task force led by Dr Gabi Müller in Nottwil, Switzerland, has investigated data from 67 patients gathered over a period of five years.

Their analysis revealed that training intensity is the most critical factor in improving the strength of respiratory muscles.

This finding should help improve the breathing of patients in their clinical routine.

Spinal Cord, July 2019

Combination therapy restores motor functions

➤ OPIOIDS HAMPER

RECOVERY In an experimental model, Professor Michelle Hook’s team at the Texas A&M Health Science Centre has proven that opioids – as in commonly prescribed painkillers – reduce functional recovery, even weeks after treatment.

They have, however, also discovered that the antibiotic minocycline has the ability to block the negative effects of opioids while retaining the analgesic effect.

Brain Behaviour and Immunity, January 2019

Scientists led by Professor Michael Fehlings in Toronto, Canada, applied a combination therapy of Chondroitinase ABC and particular stem cells in a chronic model. The result: they managed to repair the damaged insulating layer surrounding the axons (myelin layer). Motor functions were successfully restored.

Stem Cells Report, November 2018

Breathing after a single injection Dr Philippa Warren, Professor Jerry Silver, and their colleagues at CWRU, Ohio, have proven in an animal model that a single injection of Chondroitinase ABC into the cervical cord can enable strong and prolonged breathing. What is particularly noteworthy is that this treatment is more effective in chronic spinal cord injuries than in acute ones.

Nature Communications, November 2018

Large-scale data exchange project Researchers generate vast amounts of data. Some of this data is published in scientific journals, but most of it remains stored on various hard disks without ever being read. Karim Fouad of the University of Alberta in Canada and Adam Ferguson of the University of California in San Francisco in the US have launched “Open Data Commons” to address this problem. Their platform allows scientists to share negative results and experimental data with peers.

This not only facilitates the interpretation of data, but also saves time and money.

No question has to be answered twice.

NEW CLINICAL TRIALS WEBSITE A team of experts has developed the website SCITrialsFinder.net. It allows patients to enter the degree of their respective injuries and they are subsequently informed about clinical studies that could benefit their particular case. It is, however, important to remember that a clinical study is not a therapy.

Participation can, of course, improve certain functions, but one always needs to be aware of the risks involved.

LAUNCH OF ANTIBODY THERAPY The endogenous Nogo-A protein prevents damaged nerve fibres from recovering after a spinal cord injury. This is why an antibody was developed in order to improve nerve growth and functional capacities. Now the antibody in question has been admitted to the clinic!

In selected hospitals, it is being injected into the spinal cord of patients with acute injuries – six times over a period of four weeks – for the purpose of testing its efficacy.

Please find these and more Scientific News in full lenth on www.wingsforlife.com

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RESEARCH

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Mission:

Research Yale professor Stephen Strittmatter has been fighting proteins that prevent nerves from growing for years. He has been successful thus far, as an extensive clinical trial is starting now

S

cheduling a private meeting with Stephen Strittmatter is challenging. At the Scientific Meeting in Salzburg he is usually surrounded by fellow researchers, engaged in animated discussions, or busy explaining his work. We, however, managed to arrange an interview after the lunch break.

Photos: Andreas Schaad, Samo Vidic; Illustration: Gograph.com

Professor Strittmatter, what did you have for lunch? (laughs) I didn’t eat anything, actually. I spent some time exercising in the hotel’s fitness area.

Sport is important for my inner balance.

How did you come to be a scientist?

I’ve always had an interest in research, even as a child. I discovered the field of neuroscience in high school. I was fascinated by how the brain and nervous system work. I couldn’t imagine any more exciting questions than the ones posed by this field. I studied medicine alongside neuroscience. In dealing with patients, one learns many things that are invaluable in a laboratory.

Now you specialise in spinal cord injuries.

Why? Axons and their networks really impress me and I am aware of their decisive role in spinal cord injuries. After all, there is an evident problem of

interruption in this area. When I met Annette, a patient living with a spinal cord injury, I discovered her personal story. She motivated me even more to make a difference.

You have been researching for many years.

Do you always have an exact plan?

80 to 90 percent of science is predictable. There are clear rules regarding successive steps. There are, however, moments when something utterly surprising happens. It’s like a new door being blown open. You have no idea where it leads, but you really want to walk through it and discover something new. The great moments for us were when we found out more about Nogo and Nogo receptors. That was hitherto unknown.

What exactly did you and your team discover?

There are proteins that can stop the growth of axons, i.e. nerve fibres. That’s what we’ve been focusing on. We discovered a receptor for this protein and developed an interceptor molecule called the “Nogo trap”. It protects the nerve fibres’ receptors from being detected and inhibited by the proteins. ... LIFE | 25

RESEARCH

The goal: an injection that improves motor functions That sounds very complicated. Can you explain what that means in practice?

We injected this molecule into the spinal fluid of rats with spinal cord injuries. And this is where the magic happens. Almost one third of the rats were able to regain full movement, even when we began the therapy a full three months after the injury occurred.

That’s impressive! The clinical study for this “Nogo trap”, entitled “ReNetX”, starts this year. What exactly are you planning to study?

We plan to administer infusions containing AXER-204 (“Nogo trap”) to patients with chronic spinal cord injuries. We inject it directly through the lumbar spine into the spinal fluid. By doing this, our hope and aim is that the nerves surrounding the injury site rearrange and form new networks. This should improve motor functions.

Will patients feel better after this drug treatment?

That’s our goal. Firstly, we will investigate the safety and tolerability of the drug. Then, we will assess its effectiveness to improve neurological function. During experiments, we didn’t see complete recovery, but clear progress. Naturally, it’s even more complicated when humans are involved. The study participants have residual functions in their arms and hands. We do not expect them to regain the original level of functionality, but we do expect them to experience demonstrable, significant improvements.

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Why do you focus on chronic patients?

It is very difficult to predict how patients will develop in the first few weeks after an injury.

Some make more progress than others. We can merely guess. If the injury happened a year ago, the patient’s condition hardly ever changes. This means that we have a clearly defined group and can carry out the necessary tests more quickly.

And there are many chronically injured patients who need help…

Do you think about your patients during your everyday routine in the laboratory?

Yes. I often think about the many people affected.

If this drug works, it will benefit everyone suffering from a spinal cord injury. This study is designed for a specific group to obtain clear answers to our questions. If it succeeds, we can expand it.

What motivates you to keep going?

I perceive my work as a mission of sorts.

And what’s the private Stephen Strittmatter like? (laughs) My wife and I have four grown children.

We have a boat and enjoy skiing. We don’t have any grand plans like a circumnavigation of the globe. We enjoy relaxing in our free time.

Do you have dreams for the future?

I hope that multiple forms of medication will improve the lives of those affected. I hope to change medical practice and develop therapies.

In this respect, my professional and private dreams don’t differ much.

How do you define happiness?

What would make me very happy is to successfully translate my scientific findings into practice.

Neuroscientists at work: Stephen Strittmatter and Jan Schwab in the lab

Stephen Strittmatter is the director of Yale University’s Department of Cellular Neuroscience, Neurodegeneration, and Neuroregeneration. His research focuses on the re-proliferation of damaged nerves. The company “ReNetX Bio” is a spin-off of Strittmatter’s work. Wings for Life has pledged 7 million dollars to the American researcher’s project - the biggest financial contribution to date.

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SPINAL CORD INJURY

Did you know…

…what a functional hand is?

T

he words still reverberate in my ears to this day: “Mr Illek, we need to mask your fingers in order to shorten your tendons.” I was laying in the ICU with a spinal cord injury – dazed by medication and mortally afraid of what those words meant. I actually told the therapists to stop.

A little later, in rehab, the mechanics of the so-called functional hand were explained to me calmly. As a quadriplegic I am paralysed from the 5th cervical vertebra down, meaning I can no longer move my hands and fingers. My wrist and fingers would have become deformed and bent over time.

The concept of the functional hand originates from occupational therapy. Tendons and ligaments are deliberately shortened. This is achieved through special positioning techniques, muscle training, or with the help of straps, adhesive tapes, and splints. My own functional hand was fully developed after three months.

My fingers contract when I tilt my wrist upwards – it’s called the Tenodesis Effect. The movement creates a loose fist. The reverse movement opens my fingers again.

If, by the way, I should ever regain functions in my fingers, the shortened tendons can be carefully stretched back into their original state.

Wolfgang Illek suffered a spinal cord injury during a bicycle accident

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Photo: Marco Gröbner

This makes it easier for me to grasp and hold certain objects. For example, it allows me to brush my teeth alone, hold a glass of water, and use cutlery. I can reach for my mobile phone and eat an apple without assistance. All these little things wouldn’t be possible without a functional hand and would make everyday life even more difficult.

Custom-made splints and wristbands make everyday life easier

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SPINAL CORD INJURY

Gabor s

Last Dive

Gabor finds himself on his back, floating in salt water. His mind is blank, the sun is blinding. He closes his eyes as he focuses on the warm feeling on his forehead and the tip of his nose. It seems as if gravity no longer affects him. His heartbeat is calm.

Time stands still. “This is what dying must feel like,” he muses

Q

uite suddenly, time kicks back in.

Someone pulls the young man out of the water and places his body on the hard sand. Gabor can feel the ground to a certain extent, but he cannot feel his legs.

This is the day that will change his life. From now on, he is paralysed from the neck down.

In summer 2010, Gabor decided to travel to Rügen on the Baltic Sea with his friends. “I wanted to take a dip in the water one last time. I headed for the sea at a run. When the water reached knee level, I threw myself forwards to dive in head-first.” Gabor hit something hard 30 | WINGS FOR ...

with his head. It wasn’t a rock, but maybe a sandbank. “I heard a crack and immediately realised that my legs went dead.” As a reflex, the young man turned onto his back and experienced the aforementioned moment when time stood still. “The only sound in my head was the whisper of the water. It felt like I was levitating.”

Gabor’s friends rushed to his aid. “I kept on telling them not to touch me, because I knew I had broken my neck.” They carefully pulled him ashore, placed his motionless body on the sand, and called the emergency doctor. Gabor was picked up by a helicopter and taken to hospital, where he underwent 14 hours of surgery.

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Photos: Phil Pham

SPINAL CORD INJURY

Gabor recently regained minimal movement in his right hand. This allows him to operate his electric wheelchair Gabor poses cheerfully with his friends. “Our connection feels more profound today,” he says

Weeks and months passed, but Gabor’s bodily functions never returned. His injury at the level of the fourth/fifth cervical vertebra allows him to breathe independently, but he cannot move his arms, hands, or fingers at all. The same applies to his legs.

“My situation worsened significantly when I returned home,” says Gabor in retrospect. He moved into a wheelchair-accessible house right next to his parents. A 24-hour nursing service was hired to help him to bed at night,, to wash him, to brush his teeth, to dress him, and to help him eat and drink. “I was sitting at home and suddenly realised that someone had to be around me all the time, as a kind of replacement for my hands and legs. I didn’t know how to live my life in this manner.”

Gabor required time to come to terms with his disability and to accept help. It’s been nine years since Gabor’s accident. Nine years of “wheelchair time”, as he calls it, during which he had to restructure his life completely. Today, Gabor himself says that he is happy. “My life may be different, but it’s still beautiful.” He is eager to retain his positive attitude. Nevertheless, he opens up to us very honestly about his limitations. “I used to meet women at the bar.

You can’t do that in a wheelchair. It isn’t a great idea to bump into someone’s leg before starting to flirt.” Gabor’s wish for himself is to be able to move his fingers again. “The worst thing for me is actually that I can’t play guitar as I used to. It still breaks my heart, even after nine long years.

But as they say: hope springs eternal.”

“I didn’t know how to live my life in this manner” Gabor about his injury

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Gabor uses his tongue to operate his mobile phone via a touch screen Support – his sister is one of the most important people in Gabor’s life A girlfriend helps him drink – it comes quite naturally

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WINGS FOR LIFE WORLD RUN

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We

Love This Run!

Initially, the Wings for Life World Run was just a crazy idea.

Today, thousands of people support spinal cord research every year, be it at a Flagship Run or via the App, be it as an ultra-runner or a hobby jogger, by day or by night, in the sun or in the rain. All participants worldwide run against the Catcher Car at the same time – to find a cure for spinal cord injury.

You can register at:

Photo: Marcelo Maragni

wingsforlifeworldrun.com

RIO DE JANEIRO, BRASIL

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Photo: Predrag Vuckovic

ZADAR, CROATIA

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Photo: Philipp Greindl

VIENNA, AUSTRIA ... LIFE | 39

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Photo: Marcelo Del Pezo

TAICHUNG, TAIWAN

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Photo: Tyrone Bradley

PRETORIA, SOUTH AFRICA

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RESEARCH

The Vagus Nerve – A Jack Of All Trades Researchers in Texas are developing a therapy for a whole range of neurological diseases – including spinal cord injuries. Their focus is a nerve with truly astounding capabilities

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Dr Michael Kilgard, the head of the study, explains where the vagus nerve is located

Photos: Karlo Ramos, David Robinson; Graphic: Vieri Failli

W

hy don’t you place your fingers on the left side of your neck? The vagus nerve is located just below your skin. It’s a super nerve, for want of a better term.

It extends from the brain to the stomach and is involved in many vital bodily functions such as breathing, your heartbeat, swallowing, and the production of gastric acid. Approximately 80 percent of its fibres are sensory, meaning they transmit information from our organs directly to the brain. Moreover, the vagus nerve is easily accessible, which is perhaps one of the reasons why medicine has long since recognised its potential. It is utilised to treat neurological conditions such as epilepsy and tinnitus. When patients fail to respond to conventional medication, doctors turn to the vagus nerve.

They use electrical impulses to stimulate the nerve, thus significantly reducing the impact of the respective disease.

TREATING SPINAL CORD INJURIES At first glance, it may seem that spinal cord injuries have very little in common with the aforementioned conditions, but they all share

The vagus nerve is a “principal link” between our organs and the brain

one essential aspect: impaired or disrupted nerves within the central nervous system. This raises the question whether what experts call vagus stimulation also has potential to treat spinal cord injuries. “It does,” says Dr Michael Kilgard from Dallas. He is a professor at the University of Texas and has been researching the vagus nerve with his colleagues for years. They first focused on tinnitus, then on post-traumatic anxiety disorders and stroke patients. More recent experiments have proven that vagus stimulation can also be used to treat spinal cord injuries. “We started with the most common neurological disorders. Spinal cord injuries are fairly rare, but they cause severe disabilities.

With vagus stimulation, we strive to create new neural connections and restore the independence of those affected,” he explains.

The will to help seems enshrined in Kilgard’s DNA. He joined the boy scouts as a teenager and was awarded the Eagle Scout, the highest honour of the American association, for his outstanding commitment. He also has a very personal connection to spinal cord injuries. The scoutmaster for his son’s boy scout troop suffered a terrible accident two years ago. ... LIFE | 45

RESEARCH

The core project team with the exception of Dr Michael Kilgard (left to right): Dr Pat Ganzer, Dr Rob Renneker, Michael Darrow and Dr Seth Hays

He had decided to relocate to the country to enjoy his well-deserved retirement. While packing the very last box, he fell and broke his neck. He has been paralysed from the neck down ever since.

Kilgard’s aim is to significantly improve the scoutmaster’s life – and that of many others – with vagus stimulation. The team from Dallas has already proven that this is possible with stroke patients. The treatment increased their arm function significantly. “Following a stroke, progress during physical therapy is three times greater when the vagus nerve is stimulated. We expect the effect in treating spinal cord injuries to be similar,” Kilgard states.

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HOW VAGUS STIMULATION WORKS The vagus stimulation procedure itself is relatively simple, but promises great benefits for patients. The first step is to wrap electrodes around the vagus nerve. This is achieved in a surgical procedure by means of a small skin incision. The electrodes are then connected to a stimulation device implanted below the skin at breast level. At least that was the case until now.

Kilgard’s university colleagues have modernised the entire procedure from the ground up.

Today, a small chip has replaced the old wire electrodes and the large stimulator. This makes the procedure faster and gentler for the patient.

A device called “ReLay” supplies the chip with power and data. When required, it is simply

“In experiments, we were even able to triple the number of neurons in the brain that control the arm” Dr Michael Kilgard

placed around the neck in a cuff and then communicates with the chip wirelessly.

Furthermore, the bioengineers have developed an app that controls the entire system. While a therapist had to activate the stimulator in the past, sensors and the app now ensure that the vagus nerve is stimulated at exactly the right time.

NEW NERVE CONNECTIONS When the stimulator is activated, it sends gentle electric impulses to the brain via the vagus nerve. There they stimulate the regions responsible for learning - for example the learning of new movements. This is the moment something truly amazing happens. Researchers

call it plasticity. The brain learns that it has to modify its circuits in order to trigger a certain movement. The nerve cells subsequently release neurotransmitters and begin to interconnect again. “In experiments, we were even able to triple the number of neurons in the brain that control the arm,” Kilgard explains. Perfect timing is an important factor. It makes no sense to set the stimulator to a permanent current.

Instead, the impulses need to occur when the patient repeatedly performs a certain movement. Only then does the brain know that something important is happening and that it’s supposed to form new nerve connections.

“There is no point in stimulating even the slightest movements. The best are the ones that

The “ReLay” device supplies the chip with power and data wirelessly

This is where the chip is implanted (No) comparison: the chip is 50x smaller than the “old” stimulator

... LIFE | 47

RESEARCH

really count, the top 20 percent so to speak,” says Kilgard, adding: “The sensors and the app check the exercise the patient is performing. If the patient executes the movement correctly, the app activates the stimulation automatically.”

According to Kilgard, first results can be observed after just one week of training and vagus stimulation. Even in this short time, new nerve connections are formed. It doesn’t require many new connections to achieve a positive effect. “In order to improve control and sensation, we only need to make small changes to the circuit. A handful of new connections is enough,” Kilgard is convinced.

NEXT STEP: CLINICAL TRIAL Following many experiments in the laboratory, Kilgard is currently testing the system for safety in a clinical study involving 10 patients. The study is necessary because of the newly developed technology. However, he does not expect complications. “Vagus stimulation for epilepsy has been around for about 20 years. No side effects have occurred, except for a little tickle in the throat from time to time.”

At the same time, Kilgard and his colleagues are continually optimising the therapy itself.

They are exploring how often stimulation should be applied in order to achieve the greatest effect. They not only want to improve control

Dr Rob Renneker – a former member of the US Marines – is the technical mastermind behind the therapy

This joystick allows spinal cord injury patients to train. If the exercise is performed correctly, the stimulator is activated

PhD student Michael Darrow has been working intensively on the project funded by us

48 | WINGS FOR ...

Dr Michael Kilgard is one of the leading scientists in the field of neuronal plasticity. He is credited with the invention of Targeted Plasticity Therapy (TPT). Visit www.utdallas.edu/txbdc to find out more about the therapy

over arm and leg functions, but also fine motor skills. Furthermore, they are keen on introducing voice control, which would benefit, for example, patients with high-level spinal cord injuries.

“Vagus stimulation is safe, effective, and can be applied at home,” says Kilgard with visible pride. He and his team have designed the therapy to be as cost-effective as possible. Vagus stimulation is expected to find widespread application in the treatment of spinal cord injury

patients in approximately five years. Who knows what the researchers from Dallas will find out about the vagus nerve – a real jack-of-all-trades – by then?

Wings for Life supported the precursor project with 300,000 Dollar.

Contract negotiations regarding Wings for Life’s involvement in the clinical trial have been in progress at the time of the editorial deadline.

NEURONAL PLASTICITY Our brain and spinal cord modify their respective architectures slightly every single day. New experiences or impulses result in new connections between nerve cells. Existing paths are expanded, while unused ones are torn down. This ability to reconnect nerves is called neuronal plasticity. Without it, we could never learn anything new

... LIFE | 49

The baby adventure Julia has been paralysed from the 12th thoracic vertebra down ever since suffering a serious car accident. She recently gave birth to her daughter Juna. We sat down with her to chat about the experience 50 | WINGS FOR ...

Photos: Alexandra Fazan

SPINAL CORD INJURY

Julia and her partner Markus are incredibly proud of little Juna. The pregnancy was a great challenge

L

et’s start with the most important question. How are you and your daughter doing?

We’re fine. Juna is healthy, incredibly well-behaved, and sleeps a lot. I am slowly recovering from the pregnancy and the birth.

Can women with spinal cord injuries conceive naturally?

Yes. Contrary to popular belief, we conceive the same way healthy women do. The female cycle is not affected in the long term by a spinal cord injury. Ovum maturation, ovulation, and the transfer of the ovum to the uterus are not controlled by nerves, but by hormones. My partner and I wanted a family, which is why we decided to give it a go. We were so happy when it happened.

How did you experience the pregnancy?

It was very, very laborious. The level of my injury allows me to move my arms and hands, but the weight gain made it more difficult for me to

transfer from the wheelchair to the bed. I became more immobile. The wheelchair felt increasingly tight. Besides, I wasn’t allowed to sit too long in order to avoid pressure sores. As with other pregnant women, my bladder capacity decreased. Given that I’m incapable of rushing off to the toilet, I had to plan everything even more carefully. The worst thing, however, was the extreme water retention. My whole body was swollen. My hands, in particular, hurt terribly.

How did you realise “it was time” on the day you gave birth?

Many women with spinal cord injuries can’t feel contractions. They feel nauseous, get dizzy, or experience goose bumps. I didn’t really know how my body would react, especially as I still experience residual sensations. One night, I went to the bathroom and realised that my membrane had ruptured. Seven weeks too early!

I felt really painful contractions in the hospital, but was given tocolytics for a week to delay the birth. Juna was then finally delivered by caesarean section. ... LIFE | 51

SPINAL CORD INJURY

The crib is custom-made.

Julia also needs to be creative when bottlefeeding her baby

Would it have been possible to deliver her naturally?

The level of paralysis plays an important role in this context. Many of those affected can no longer press. I might have managed with the help of doctors and midwives, but I felt the risk was too high. The baby could have got stuck in

things in terms of dealing with Juna. Given that she was born prematurely, we had three weeks to get used to each other in the ward.

Now the small family has arrived at home…

Exactly, and we have settled in well. The changing unit has been lowered and the

“I hope Juna can accept my disability“ the birth canal and failed to get enough oxygen.

That would have been too risky. The caesarean section was a conscious decision I made in advance.

customised crib allows me to pick Juna up without help. I can even push her pram with a Segway. If you’re restricted and can’t move your legs, you have to get creative…

How did it feel to hold your baby in your arms for the first time? (smiles) It was simply indescribable…

If you could make a wish…

I want our family to be happy. I hope Juna will grow into a healthy, strong girl with a unique personality and character. I hope she can accept my disability and won’t be too sad when I can’t join her for her first steps – or follow her first outing on a bicycle or skis.

What about the time you spent in hospital?

I had her little bed placed right next to mine and changed her nappies between my thighs.

Hospitals are not prepared for mothers with spinal cord injuries. I had to learn so many 52 | WINGS FOR ...

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KNOWLEDGE

The History of Spinal Cord Research In the past, people with a spinal cord injury could not even be treated.

Today, the first patients are taking their own steps again - thanks to research.

A chronicle of the most important events and insights

Dark times

2500 BC THE FIRST TRACE The first written mention of spinal cord injury 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 spinal cord injury and develops a stretching bench for therapy. Several centuries later, the Greek doctors Aretaeus and Galen define the different levels of spinal cord injury .

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 at least try to regenerate. However, without success.

54 | WINGS FOR ...

1911 IMPROVED MODEL The American neurologist Alfred Reginald Allen perfects the experimental model for spinal cord injury. It is essential for later research and is still in use today.

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

Photos: Wings for Life, private, Wikimedia

Beginning of research

An explanation of the technical terms can be found here: wingsforlife.com/glossary

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 for people with spinal cord injuries increases. He develops treatment methods and is considered by many to be the founder of the modern rehabilitation of paraplegics.

Sam David

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.

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!

The dogma “spinal cord injury is incurable� is overturned

... LIFE | 55

KNOWLEDGE

Explore new approaches 1990 FIRST SPINAL CORD INJURY RECOVERY The Swiss neuroscientists Lisa Schnell and Martin Schwab succeed in promoting 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.

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.

56 | WINGS FOR ...

1991 HOPE FOR CHRONIC PARAPLEGIA The American neuroscientist John Houlé shows that axons continue to regenerate long after a spinal cord injury. This is 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.

New findings 2004 PLASTICITY Martin Schwab describes plasticity in spinal cord injury. This means that nerve endings form new links. Pre-existing circuits are used, which are still intact after the injury.

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).

2005 STEM CELLS For the first time stem cells are used in spinal cord injury treatment. 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 physician and neuroscientist Jan Schwab finds out that spinal cord injury affects the immune system, which impedes recovery.

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

Steps to humans 2010 FIRST STUDY ON EMBRYONIC STEM CELL THERAPY A clinical trial tests the effects of embryonic stem cells on subacute spinal cord injuries. In 2015, this approach is 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.

... LIFE | 57

KNOWLEDGE

2012 NEUROTECHNOLOGY French neuroscientist Grégoire Courtine presents a technology that allows rats to walk despite severe spinal cord injuries. 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, study the pressure in the spinal cord of recently injured patients. Optimal pressure conditions should reduce the consequences of spinal cord injury.

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 project. In the same year, Jerry Silver can restore breathing in chronic model of spinal cord injury .

2019 CLINICAL STUDY American neuroscientist Stephen Strittmatter launches a clinical study involving patients with chronic spinal cord injuries. A protein is injected into the spinal cord. The aim is to promote plasticity and restore functions.

58 | WINGS FOR ...

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RESEARCH

The

Axon

Whisperer Fine, we may be exaggerating a little. However, neurologist Zhigang He is one of the first people to succeed in regrowing nerve fibres – i.e. axons – with the help of a specific molecule. We sat down for a chat with the highly respected top scientist

60 | WINGS FOR ...

... LIFE | 61

Photos: Andreas Schaad, Martin Lugger

RESEARCH

Zhigang He at the annual Wings for Life Scientific Meeting

Professor He, anyone interested in neurology and spinal cord research inevitably stumbles upon your name. Was this your childhood dream? (laughs) No, not really. I studied medicine in China. I first encountered many kinds of patients during an internship and realised that there were no treatments for them. Back then nobody even understood what was behind these clinical problems such as spinal cord injury. It soon became clear to me that I wanted to effect change. That’s why I went into basic research.

What was so exciting about that field?

When you conduct basic research, you soon realise how many questions are still unanswered.

Finding new answers is always exciting.

Could you elaborate on your greatest discoveries?

A spinal cord injury disrupts the connection between the brain and the rest of the body. This constitutes a highly complex situation. From the very beginning, the most important question 62 | WINGS FOR ...

FACT SHEET Zhigang He, who was born in China, is a professor of neurology and Ophthalmology at Harvard Medical School. He directs a research laboratory focusing on neural repair in Boston Children’s Hospital. Zhigang He is married and has two daughters

was how to restore the aforementioned connection. One has to realise that evolution took several million years for the body to function so perfectly. We published a paper on PTEN ten years ago. If this protein is eliminated, axons can regenerate.

What exactly is this PTEN? Cells grow. It’s in their nature. The enzyme PTEN suppresses the constant growth of cells.

Eliminating this “growth inhibitor” makes nerve

“There will be treatments and not every injury will result in chronic suffering” Dr Zhigang He

growth possible. But what can be so enormously important for parts of the spinal cord also harbours risks.

Eliminating PTEN in glial cells can result in an uncontrolled activation of the cell cycle and thus the forming of tumours. Now we need to work on a safe strategy that has similar effects on nerves as PTEN, but without causing any side effects.

What are you currently working on?

For example, we recently discovered that the molecule osteopontin can render nerve cells more susceptible to the effects of certain growth factors. A combined therapy of molecules and factors has already revealed a successful regeneration of axons in a cross-sectional model, thus mimicking the effect of PTEN. What are your next steps in the laboratory?

The laboratory is where we make new discoveries in controlled circumstances.

Translating everything we have discovered in the laboratory into clinical applications for patients remains a challenge. We published a paper revealing that we managed to reawaken dormant axons in a mouse last year. These findings have not been widely appreciated yet, but I believe that this approach has a great possibility of helping patients. We are working actively in this direction.

It seems every answer leads to another question… Researchers are inquisitive by nature.

That is our job.

How will spinal cord research change over the next few years?

Spinal cord research has made enormous progress in the last 10 to 15 years. There have been huge leaps in technology and clinical understanding. This development will continue in the coming years. I don’t necessarily believe that complete functional recovery after a spinal cord injury will be possible, but the procedures could resemble those we have for cancer. There will be treatments and not every injury will result in chronic suffering.

Does this mean research will become more clinical in its approach?

Every little piece, every discovery, contributes to the big picture. Based on the data we already have, I am cautiously optimistic. I hope that we will be able to translate many findings into clinical applications.

Do you ever switch off and relax?

I used to ski a lot. Boston is a perfect location for that. I took up snowboarding about seven years ago. It helps me clear my head. I also enjoy playing squash with my daughters. It is great to see they are getting better and better.

What is your vision for the future?

I hope that our research will help patients before I retire. That is my dream.

How much time do we still have?

It won’t take too long, hopefully. The sooner the better …

... LIFE | 63

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... LIFE | 65

PERSONAL

Column

BY ST E FA N I E S C H WA R Z

And Lukas has to live with it.

He knows that he won’t be scaling a mountain in summer, and that he won’t be playing volleyball or jumping into a lake. He knows that he will be forced to sit in the shade for longer periods of time to protect his skin. Lukas tells me about his girlfriend. They have been a couple for ten years, but now a bulky wheelchair has come between them. We talk about love, destiny, and dreams.

It feels like I’ve heard Lukas’ story before. People have been telling me how their accidents affect them for more than four

66 | WINGS FOR ...

years. They try to explain how it feels when you suddenly lose your freedom. I start every interview with a blank piece of paper. I leave with a long list of memories, thoughts, and hope.

But something is different when I return to the car this time.

I just sit there without starting the engine. I close my eyes and exhale very slowly. I’m so infinitely grateful for feeling fine. Everyone I care about is healthy. I can simply return to my intact world. I fasten my seatbelt and turn the key. But suddenly I start crying bitterly.

Hot tears trickle down my cheeks and stain my light-grey sweater.

Lukas could be my husband. Or my

brother. Or a friend.

I drive off. The rehab facility is getting smaller and smaller in my rear-view mirror. I’m driving slowly, not even 35km/h. Maybe I’m trying to stall. Maybe because I know that this day is coming home with me, no matter how fast I may drive.

I start to wonder whether this is the right job for me, whether it’s good for me that everything around me is always so vulnerable. People open up to me. They bare their innermost in such a raw and unembellished manner.

They allow me to come so close.

Even after a couple of years I cannot get used to their shit situation, their pure honesty, and their admirable strength. That’s probably a good thing, in a way.

My mobile phone vibrates. Lukas writes: “I will never forget this afternoon.” At this moment, on some random country road somewhere near Vienna, I realise that what I do is actually invaluable.

Stefanie was working as an editor when a wheelchair dancer shared her story with her during an interview. She applied to Wings for Life and has been responsible for our texts ever since

Photo: Tanja Schalling

I

’m in a rehab facility for patients with spinal cord injuries. Everything here reminds me of a hospital that is starting to show its age. Yellowing, scuffed walls. Wide, bare hallways.

The smell of cold fruit tea and disinfectants lingers in the air. I meet Lukas in a stuffy patients’ lounge. He tells me about how he fell from a ladder while he was at work. So trivial, yet so devastating.

He has been paralysed for a little more than five months. 159 days.

3,816 hours. 228,960 agonisingly long minutes of not being able to go to the toilet, not being able to stand up, let alone being able to walk. Nothing from the chest down works anymore.

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You

100% of all donations fund life-changing spinal cord research projects

Please continue to support our cause DONATION ACCOUNTS INTERNATIONAL Bankhaus Carl Spängler & Co, Salzburg, IBAN: AT27 1953 0001 0001 1911 BIC: SPAEAT2S Beneficiary: Wings for Life – Spinal Cord Research Foundation, Fürstenallee 4, AT-5020 Salzburg UNITED KINGDOM HSBC, Account No: 83882101 Sort code: 40-05-30 IBAN: GB72 MIDL 4005 3083 8821 01 BIC: MIDLGB22 Beneficiary: Wings for Life, Seven Dials Warehouse, 42-56 Earlham Street, London WC2H 9LA, UK USA Donate via Check to: Wings for Life USA - Spinal Cord Research Foundation Inc., 1630 Stewart Street, Santa Monica, 90404, CA