Recap of #Working2Walk19 - Reeve Foundation

After several wonderful days at Reeve HQ for my first onsite visit and formal introduction to the team, I arrived in Cleveland energized for the Unite 2 Fight Paralysis 14th annual Working2Walk symposium. This was my first SCI science and advocacy conference. A chance at the outset of my journey as the first-ever CSO of Christopher & Dana Reeve Foundation for intense learning, ideating, and networking with a cross-section of the SCI community, including researchers, families, companies, and people with lived experience.

Science and advocacy conferences are familiar terrain coming from the rare disease world. I’ve attended dozens over the years. These are the places where community bonds form; where promises are renewed; where hope is restored; and where the troublemakers -- the “I have another question” askers -- make their presence felt. It’s an opportunity to forge a common cause. In short, my initiation into the SCI tribe.

Day 1 of #Working2Walk19:
Matthew Rodreick, Executive Director of U2FP and conference emcee, offered opening remarks in an enormous ballroom that would accommodate a wedding the next evening. Each science session featured three speakers giving 20-minute talks followed by a moderated panel discussion. I sat at a table in the front with Brian Keeter of The Walk On Foundation and David Darrow, MD, from the Department of Neurosurgery at the University of Minnesota Medical School. We were joined by my colleague Kim Beer, Director of Policy at the Reeve Foundation.

Darrow started things off with an update of the E-STAND trial, which stands for Electrical Stimulation After Neurological Damage. Eleven patients have been implanted to date.

The first question was from Corinne Jeanmaire, the founder of EndParalysis, about accelerating the translation of what’s broadly defined as FES (Functional Electrical Stimulation) to more people living with SCI. I’m only six weeks on the job, but I understand the frustration. I’ve heard this voice before over the years. It’s a combination of urgency and resignation fueled by countless cycles of anticipation and disappointment. I know those questions have been asked of experts before (likely many times), but never fully understood or satisfactorily answered.

Estim, neurostim, electroceuticals, prototype FES devices, and even safe but commercially discontinued devices have been used for decades. Simply put, the rate of translation is way too slow. During the Q&A someone asked if money is the rate-limiting step. Are the safety risks of implantation and subsequent tune-ups tolerable? How do we rapidly and responsibly grow the number from 50 implanted with neurostim devices? For example, a device for bladder control was once available in America but is no longer manufactured here, falling through the cracks of the humanitarian use device (HUD) regulatory pathway and languishing without a commercially viable business case.

The SCI panel opened my eyes to the visible and the invisible consequences of a traumatic spinal cord injury. There are 1.3 million individuals living with spinal cord injury and over 5.4 million Americans living with some form of paralysis. Car or motorcycle accidents, gunshots on the battlefield and home front, skiing, snowboarding, diving accidents. Rich and poor. White and black. Faces and stories we hear, and many more we never see. It’s an injury that doesn’t discriminate and can happen at any time, anywhere.

There is an able-bodied assumption that walking is the number one priority of the SCI community. While it’s certainly a critical priority and one the Reeve Foundation considers to be a top mission, people rightfully want to control their bladder and bowel function and autonomic dysreflexia, neutralize chronic pain and have an orgasm. And, they want increased movement and mobility. The pursuit of neurotechnology should never lose sight of organic solutions that address all challenges associated with paralysis, as well as the root cause of SCI.

The talk by Vivek Pinto from the FDA got me thinking. Can we address the lack of natural market forces for SCI devices with targeted federal regulation already proven to unleash innovation? The Orphan Drug Designation has stimulated the development of small molecule drugs and biologics because of the seven-year market guaranteed exclusivity, waiver of user fees, and tax write-offs for R&D. Why can’t there be an Orphan Device Designation? Or make it the ODDD: Orphan Drug & Device Designation? Are there other regulatory advantages of orphan status for SCI communities to consider in the US and other countries?

The second afternoon session was all about CSPGs as a therapeutic target for neuro-recovery and neuro-regeneration. The speaker, Jessica Kwok, was unfortunately unable to join us. CSPGs is short for chondroitin sulfate proteoglycans. The discovery of CSPGs as inhibitors of neurite extension in cell culture experiments, and as inhibitors of axonal regrowth in post-acute SCI rodent models by Jerry Silver’s group at Case Western Reserve University is currently being developed by a scrappy Canadian biotech called NervGen. Their clinical candidate is an oral peptide that specifically blocks the binding of CSPGs to their receptors (PTPσ) on the growing tips of axons. Could a combination of NervGen’s drug candidate and local delivery of chondroitin sulfatase, the enzyme that naturally digests CSPGs, spur regeneration better than the agent alone?

Day 2 of #Working2Walk19:
The first morning session of Day 2 was dedicated to stem cell therapy and stem cell grafts with 3D-printed biomaterials. There was even a cameo from spinal cord organoids, which seem like excellent models for drug repurposing. It was rock star lineup: Lana Zholudeva at Gladstone Institutes, Alina Garbuzov from Mark Tuszynski’s lab at UCSD, and Ann Parr from the University of Minnesota Medical School.

I remember the first stem cell hype cycle dating back to 2001, but I’m very bullish about the therapeutic potential of stem cells today and have renewed hope after hearing from these seasoned scientists. Technical challenges remain, like the intrinsic variability of contusive injury rodent models as testing beds for stem cell therapies (i.e., no two injured rats are the same). What about the risk of neuromas, asked discussion moderator Sasha Rabchevsky? Kill switches like those being developed for CAR T cells could be a solution.

The talks by Phillip Popovich and Dana McTigue, both from Ohio State University, covered the secondary consequences of a spinal cord injury on the gut microbiome, liver, and cardiovascular health. When I think about the ripple effects of a traumatic injury on so many organ systems and physiological processes, I see opportunities to achieve parallel improvements in quality of life with interventions as simple and relatively safe as probiotics.

The second to last session featured a talk about transcutaneous spinal cord stimulation (TSCS) with rehab by Rebecca Martin from the Kennedy Krieger Institute. Hal Hargrave and Mike Alpert from The Perfect Step talked about the Claremont Club in Orange County, CA, which has state-of-art equipment and professional staff serving not only the SCI community, but also people living with ALS, MS, and neuromuscular conditions. Harvey Sihota and his colleagues from Neurokinex in the UK are yet another example of an entrepreneurial, bottom-up Community Fitness and Wellness (CFW) facility. Exercise as medicine is basically a synonym for activity-dependent plasticity which, in its simplest definition, is another way of saying rehab. Every drug or device will require a foundation of rehab, and high-quality rehab will be delivered in SCI wellness centers by talented and devoted physical therapists, trainers, and other support staff. The greatest challenge, of course, is developing a sustainable business model for these CFW sites that allow 100% subsidized access by anyone with a SCI who can’t otherwise afford to pay.

The final session was a discussion of what’s happening since SCI 2020, the conference hosted by NIH eight months ago to engage stakeholders around the next decade of SCI research. We can all identify the stakeholders. We can all spot the low hanging fruit. We all know the ultimate destination. The question on everyone’s mind that was asked by someone injured a year ago—what is the roadmap?

My immediate priority as CSO for the Reeve Foundation is to create a comprehensive, consensus-driven, multi-faceted, multi-year SCI Cure Roadmap that also addresses the cheapest and most effective solution: prevention. Developing this Roadmap is a highly complex optimization and prioritization of goals already percolating in the SCI community. It’s my job and the job of the team I’m recruiting at the Reeve Foundation to enumerate specific milestones, timelines, budgets and contingencies – a dynamic SCI Gantt chart. #Working2Walk19 conference was my first chance to pressure test early ideas, as well as find intellectual sparring partners and reality checkers to constantly keep me honest and focused.

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About the Author - Ethan Perlstein

Ethan Perlstein

The opinions expressed in these blogs are the author's own and do not necessarily reflect the views of the Christopher & Dana Reeve Foundation.