Speaker Spotlight: Ann Parr & Jessica Kwok (Working 2 Walk)

Previously, we described the portion of this year’s Symposium (register now!) that will be devoted to stem cell research strategies (Alina Garbuzov and Lyandysha Zholudeva). Dr. Ann Parr, from the University of Minnesota will provide a presentation on combining neuronal progenitor cells (cells that give rise to the many cells found in the central nervous system) with a 3D printed scaffold that show signs of improved formation and connectivity.

Jessica Kwok, from the University of Leeds will present on her studies using a small molecule to address the lesion that forms after injury and inhibits regeneration and plasticity. This repurposed molecule which is used in the treatment of some rare brain diseases appears to show some efficacy in restoring lower limb functions in animal models. Both of these speakers will highlight some of the regenerative strategies being investigated. We expect both of these presentations to generate strong interest and provoke lots of questions.

Speaker Spotlight

Regionally Specific Spinal Neural Progenitor Cells in a 3-Dimensional Bioprinted Scaffold: Why Specificity Matters

Ann M. Parr, MD, PhD | Assistant Professor, Department of Neurosurgery, University of Minnesota

The Problem: While many have focused on therapies for subacute spinal cord injury (SCI), chronic SCI remains an unmet need, with an estimated 288,000 people currently living with chronic SCI in the US. We and others have transplanted non-specific neural stem cells into the injured spinal cord in various animal models and have reported functional recovery. Cell replacement, neuroprotection, modulation of the environment, and remyelination have all been proposed as mechanisms. However, it is unlikely that all of these will also be beneficial in chronic SCI, since these patients are outside of the time frame of benefit, and thus new mechanisms such as the establishment of a relay network should be pursued.

The Plan: Therefore, we propose a combinatorial strategy of bioprinting regionally specific spinal Neural Progenitor Cells (sNPCs) in a 3D printed scaffold. Regional specificity is crucial, as evidenced by recent literature and our own experience (i.e. we need to utilize cells that are normally found in the spinal cord rather than the brain). We propose to directly print these cells in precise locations within a patient specific scaffold that fits into the lesion cavity.

The Results: We can now create these human sNPCs directly from a patient’s own tissue through the use of induced pluripotent stem cell technology to avoid immune rejection. Our cells can communicate with other cells, a key feature in using them as a relay. Our cells also have the ability to form limited “mini spinal cords” as they regenerate. Printing them into the scaffolds provides protection during transplantation, guidance for regenerating axons, and increased formation of neural networks. This strategy could be a future treatment for chronic SCI, but work still needs to be done in optimizing the scaffold biomaterial and providing evidence to regulatory agencies that this would be safe and effective in humans.

Team: Ann M. Parr, Michael C. McAlpine, Nicolas Lavoie, Daeha Joung, Manuel Esguerra

Funding Sources: Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program, Morton Cure Paralysis Fund, Cure Paralysis Now, Spinal Cord Society

Links to Publications: https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.201801850, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802631/

Non-Invasive Treatment for Functional Recovery after the Spinal Cord Injury

Jessica Kwok, PhD | Associate Professor, University of Leeds (United Kingdom)

After spinal cord injury, there is a strong upregulation of neural inhibitory molecules around the lesion scar preventing regeneration and neuroplasticity. One of the key molecules is chondroitin sulphate proteoglycans (CSPGs).
In addition to their presence at the lesion site, CSPGs are also present in perineuronal nets (PNNs) under normal physiological condition. PNNs are dense pericellular structures that envelop sub-populations of neurons throughout the central nervous system providing stabilisation of circuitry and thus regulation of plasticity. To enhance recovery after spinal cord injury, therapies aim to promote regeneration of severed axons and the plasticity of surviving circuitry. Enzymatic removal of CSPGs using chondroitinase ABC (ChABC) opens a window of plasticity enhancing functional recovery, particularly in spinal cord injury models. However, there are significant hurdles translating ChABC into clinical use due to its bacterial enzymatic nature.
We have recently repurposed a small molecule, perineuronal net inhibitor (PNNi), which provides a non-invasive strategy in down-regulating CSPGs in the CNS. Daily oral administration of PNNi successfully down-regulates CSPGs in the injured spinal cords and PNNs in rodents. This downregulation enhances the recovery of hindlimb functions when combined with rehabilitation. We are currently exploiting the use of PNNi in enhancing recovery in chronic spinal cord injury.

Team
Sian Irvine 1, Sylvain Gigout1 and Jessica Kwok 1,2
1 Faculty of Biological Sciences, University of Leeds, Leeds, UK
2 Institute of Experimental Medicine, Czech Academy of Science, Prague, Czech Republic

Funding Sources
International Spinal Research Trust, Wings for Life, Medical Research Council

How did a handful of dedicated advocates pass $4M for SCI Research in one year ($3M in OH and $1M in PA)?

Come to Working 2 Walk (October 4–5 in Cleveland) and hear Jeni Belt, Peter Nowell and Allie Leatherman (from Ohio), and Jake Chalfin (from Pennsylvania) share their experience being a part of our Cure Advocacy Network. It’s a conversation you won’t want to miss!

Register Now

Online registration closes Monday, September 30

Stacy Elliot — (Working 2 Walk 2018)

We have another video up from last year’s Working 2 Walk Symposium in Vancouver, to help get you motivated for this year. Check out Dr. Stacy Elliott’s presentation entitled: Sexual and Fertility Rehabilitation Following SCI. Dr. Elliott gives an overview of sexual function research and entertains some interesting questions from last year’s audience. Definitely worth watching.

Dr. Elliott’s presentation is stored in our Vimeo album, and is currently featured on the Video Library page of our website.

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