One of SCI research’s biggest and most heated disagreements may be nearing a resolution. At issue is: After a spinal cord injury, what exactly prevents a surviving axon from making its way through the injury site to reconnect with surviving axons on the other side?

Over years of heated debate, two camps have emerged. We’ll call them Team Scar and Team Poison. Team Scar is positive the problem is molecules produced by astrocytes, which are one of the three main kinds of spinal cord cells. Team Scar asserts these molecules form a barrier that is both physical and chemical — a scar.

Team Poison is just as certain that the culprits are different molecules found in myelin, the white coating that serves as a wrapper around healthy axons. Team Poison’s proposition is that these myelin-made molecules are toxic to growing axons.

Both kinds of molecules, those being studied by Scar and Poison, are part of a normal, healthy nervous system and, after injury, one or both of them act to prevent recovery. In my last column (“Three Molecules and a Mom,” January 2020), I told you about a company called NervGen, which was recently formed specifically to deliver a treatment based on the scar theory.

This column is about another company — named ReNetX — also recently formed to deliver a treatment based on what Team Poison scientists have been working on since 1988.

Meet Emily

Because I have trouble sometimes wrapping my head around the long time frames of research, I’m going to introduce a child to help me keep track of the passing years. Let’s call her Emily. In 1988, while Team Poison scientists are beginning their long, frustrating effort to figure out exactly which of the hundreds of protein molecules in myelin are poisoning axons, Emily is born. The scientist leader of Team Poison is in Zurich, Switzerland; his name is Martin Schwab.

In 1994, after six years of effort, the scientists in Schwab’s lab have found nothing. Emily is entering first grade. During that time, other labs have begun to look for the toxic molecule. That year, two of them hit the jackpot. They find a molecule they believe is the culprit, and they name it MAG. At first, the Zurich team panics because they believe they’ve been beaten to the goal. Soon, though, they produce evidence that MAG is not the only poison in the myelin. Sadly for us, there are multiple varieties of toxic molecules in myelin.

By the time Emily enters sixth grade in 2000, another one of those axon-poisoning molecules has finally been identified in Switzerland and simultaneously at Yale University in New Haven, Connecticut. It’s taken 12 years to get from the initial search to the publication of a paper in Nature that maps the molecule’s genes and gives it a name: NOGO.

A year after that, scientists at Yale produce a paper that identifies a receptor for NOGO; this receptor is a particular molecule that acts as a sort of lure for the toxin. It’s January 2001, and in a few weeks Emily’s father will fall and break his neck. Emily is real, of course. She’s my daughter, and that year she will celebrate her 13th birthday with our friends in the cafeteria of a trauma center.

The finding of the receptor is a hugely important step, because it invites our Team Poison scientists to get to work finding a way to neutralize that receptor, to make it chemically invisible. The theory is that if the NOGO can’t see the receptor, it won’t bind to it, and the axon will be able to grow safely past.

But how does a theory — even one backed by solid science — go from scientists publishing papers to treatments for real people? The simple answer is, it takes money. Lots of it.

Wings for Life

Two years after the Yale team discovered that NOGO receptor, a young Austrian named Hannes Kinigadner broke his neck. Hannes, though, was the son of a two-time world champion motocross racer named Heinz. In 2004, Heinz Kinigadner and a friend formed a nonprofit called Wings for Life. The friend was Dietrich Mateschitz, and Mateschitz is the man who founded the company that produces the energy drink, Red Bull. He has, to put it mildly, lots of resources.

Wings for Life has only one mission: to find effective treatments and cures for spinal cord injury (see sidebar). In 2017, Wings for Life committed to supporting Team Poison’s NOGO Inhibitor project via the newly formed company, ReNetX, with $7 million — enough money to build and carry out a clinical trial on people with chronic spinal cord injury. A November 2017 press release explained the critical role the funding would play:

“Our mission is to find a cure for spinal cord injury,” says Jane Hsieh, executive director of the Wings for Life Accelerated Translational Program. … Hsieh describes the funding as a critical bridge to help ReNetx Bio cross what is known as the “valley of death,” to advance programs to key proof-of-concept milestones needed from a large-scale clinical trial to spark additional investor and industry engagement to advance promising treatments for patients.

Let’s slow that down.

First, “cross the valley of death” means to get proof-of-concept milestones in place. That involves, among other things, showing that this treatment, which has restored full mobility to one-third of the rats that got it, works in at least one human being.
Second, set up a large clinical trial that will bring in investors willing to place bets on that treatment.

Third, use the investors’ money to build the medical infrastructure that can deliver treatments.

You can be part of this project by volunteering to be in the safety trial (see Resources).

“Are we there yet?” It’s a sentence my young Emily must have asked a thousand times on car rides. By the time her 33rd birthday comes around in 2021, she just might be able to read about a person who was successfully treated with a therapy that has been in the making since the day she was born. And then we’ll know whether it was Team Scar or Team Poison — or both — that was on the right track.

*****

The World Run

When one of the founders of your nonprofit is known for founding a company with a reputation like energy drink giant Red Bull, there is an expectation that you will host creative fundraisers. Wings for Life has surpassed that expectation with the World Run, the innovative annual race it launched in 2014. In the Wings for Life World Run, there’s no set time and no set distance; instead, each runner starts their race at exactly the same moment all over the planet, at one of the 35 designated starting points for each 100km course.

The runners get a 30-minute head start. Half an hour after the race begins, a “catcher car” leaves each starting point, traveling the course at just under 9 mph. When the catcher car passes a runner, that runner has been “caught” and is eliminated. The race ends when there is only one runner left on each course, and the distances covered by each are compared to find the overall champion.

The World Run is a bit of a metaphor-generator. It’s a race to get to a treatment before one more person gets “caught” by paralysis. It’s a global example of the kind of tight scientific coordination that will be necessary to get a therapy to market. It’s a visual reminder that efforts are underway to find those therapies in every corner of the planet, simultaneously.

All the costs of mounting this elaborate international event are born by Red Bull, and all the entry fees go directly to support the science the Wings for Life scientific board has identified as most promising.

Resources
• NervGen, nervgen.com
• ReNetX, renetx.com
• ReNetX Clinical Trials, renetx.com/clinical-trial.html
• NEW MOBILITY, “Three Molecules and a Mom,” newmobility.com/2020/01/three-molecules-and-a-mom
• Wings for Life, wingsforlife.com/en
• Wings for Life World Run, www.wingsforlifeworldrun.com/en