Navigating U2FP’s Science & Advocacy Symposium, Part 3

by Sam Maddox — Scientific Advisory Board Director
Originally published Aug 2, 2021

Save the date: this year’s Symposium is October 22 and 23 in Salt Lake City, Utah. You can view the current agenda here , our speaker lineup here , and hotel info here . Then go register online here .

The Symposium is not a TED talk or a lecture series. It’s an interactive partnership of people with a stake in the SCI world, including scientists, clinicians, funding agencies, biotech people, etc. The SCI community, those living with the injury, are a key part of it; you are encouraged to share your story and voice your priorities. Don’t miss this opportunity to engage with the experts during the sessions, during breaks or later in the hotel lounge. Don’t be shy — participants welcome this chance to meet you too, it keeps their endpoints, and motivation, real.

R+R+R = R.
We’ve defined three very broad research approaches to promote recovery in chronic spinal cord injury: previously, we covered Replace (add cells) and Rejuvenate (activate dormant nerve networks).

Let’s now consider Regeneration — the functional regrowth of spinal cord nerve fibers (axons). Axons are the long fibers that may travel down the cord, responsible for major muscle activity. Injury causes the axons to shrink back toward the cell body. Nerve cell bodies want to grow their axons after injury, and very much try to. But axons are confronted by an injury site that has become quite toxic and sealed off to growth. And it’s not just the inhibitory environment. The nerve cells don’t seem to have the juice to grow with the vigor they had when the embryonic and developing nervous system was first wired up.

So, the challenges are to unblock the axon pathways and to repower the cells. Downstream, of course, the new axon must eventually hook up with the appropriate connection to restore functional circuits.

In theory, it’s possible: growth machinery can be restarted by recoding developmental genes; barriers can be overcome by using molecular decoys or drugs to remove scar; long axons can be cultivated to extend far across the injury site, perhaps along a scaffold. (As we recently discussed, Michael Lane, from Drexel, has shown the beneficial effect of transplanting a specific stem cell subtype in restoring breathing to a paralyzed rat; the new cells wire in but also enrich the poisonous injury milieu. Jacob Koffler, from UCSD, has grown stem cells on 3D printed scaffolds. Both are in the spinal cord regeneration business — not entirely by building new circuits, but by adding support to existing circuits).

The final part-making functional connections between the spinal cord and muscle targets that might be 18 inches away- they’re working on it.

This is very difficult biology and let’s be clear, it’s a long way from human use. What’s clear to scientists is that a single approach probably won’t be the answer; regeneration will almost certainly be in the form of combination therapies along the stages of axon growth.

The theme of regeneration — and collaboration — is woven through the Symposium agenda.
Here are a few examples of how regeneration works:

Collaboration Matchmaking
At the 2020 Symposium U2FP featured a panel called Accelerating Translation with Porcine Models of Spinal Cord Injury: An Invitation to Collaborate. Candace Floyd, a neuroscientist from the University of Utah was joined by University of Toronto scientist Molly Shoichet and University of Texas researcher Nick Jefferies. Shoichet described a new formulation for a scar-busting drug (chondroitinase, or chase) that promotes regeneration much better than other less stable versions of chase. Jefferies talked about his well-developed veterinary model for spinal cord injury; he has used chase to help paralyzed dogs.

Here’s the collaborative payoff: Shoichet and Jefferies, who previously did not know of each other’s work, got together and wrote a grant to try her new chase formula in his paralyzed dogs.

Floyd returns in 2021 for a Friday morning panel (October 22) addressing Strategic Relationships. She will no doubt mention another potential alliance that evolved from last year’s Symposium. Floyd specializes in using larger animals (pigs) to test therapies usually done in mice or rats. Rodent research is valuable but in many ways not relevant to human SCI. Primate research is obviously preferable but harder to do, more expensive, and more exposed to animal rights activism. Pigs, well, they’re sentient beings too. But as long as people still consider them food, they will play a significant role in treatment development.

The group, also joined by Silver, is currently lining up funding for a multidisciplinary combination chronic SCI study in early 2022: use the peptide drug (NervGen/Silver) to free spinal cord axons from their bonds, add in epidural stimulation (Darrow/Parr) to optimize their growth and plasticity -try it in a clinically relevant large animal model (Floyd).

Other panelists on the Strategic Collaborations panel include Sabhya Rana, a neuroscience post-doc from the University of Florida and Warren Alilain, an Associate Professor at the University of Kentucky’s Spinal Cord and Brain Injury Research Center . (Alilain can be expected to weigh in on any discussion of chase; he’s studied it for years. He was lead author with Jerry Silver in a 2011 paper in showing that chase induced very cool recovery of breathing in a chronic model of SCI.)

Rana and Alilain are on the program to discuss the International Online Spinal Cord Injury Research Seminars (), created in 2020 to keep scientists in touch with online research seminars despite pandemic related travel restrictions. It’s a great idea which has gotten lots of support in the research community, and they want to make sure the SCI community participates in upcoming presentations.

Incubating Innovation
A Saturday panel, Discovery to Market, is about the process of bringing an idea from the lab to the marketplace and clinic. Featured are two companies, , a Symposium sponsor with spinal cord stimulation technology in clinical trials, represented by co-founder scientists Gregoire Courtine and Jocelyn Bloch, and CEO Dave Marver; and , the Utah firm that makes the implant arrays used for brain to computer control, in the person of Florian Solzbacher, co-founder and chairman.

Praxis pointed out the importance of tackling spasticity and pain. I had initially focused on the KCC2 enhancer to cure paralysis, but now I have learned that helping with pain and spasticity is as important as motor function.The support from Praxis has been truly far-reaching. Praxis supported our fundraising efforts and is helping to build out our regulatory, clinical and IP strategies. We are incredibly grateful for this mentorship and coaching

Next time: the 2021 Symposium looks at the science of sexual function, the keto diet and SCI, and the facts about exercise.

Originally published at https://u2fp.org.