Long Term Neural Stem Cell Transplant to repair Spinal Cord Injury: neurogenesis, gliogenesis and axon persistence

Paul Lu PhD Associate Researcher University of California, San Diego

Paul Lu, PhD, Associate Researcher, University of California, San Diego – School of Medicine
My primary research focuses on gene therapy and neural stem cells for spinal cord injury. My early studies focus on ex vivo gene therapy with neurotrophic factors to promote axonal regeneration into a cell graft placed into the spinal cord lesion site. However, regenerated axons rarely exit from the graft. To enhance axonal exit from the graft, our team uses combinatorial approaches, including modifications of both the injured environment with neurotrophic factors, and intrinsic neuronal growth capacity by alteration of intrinsic neuronal gene expression. Both sensory and motor axons regenerate beyond the lesion site with such an approach.

Video provided by U2FP:

Posted in Chronic Spinal Cord Injury Research, Regenerative Medicine, Spinal Research, Stem Cell Research | Tagged , | 2 Comments

Molecular controls over corticospinal motor neuron segmental targeting

Authors: *V. V. SAHNI1, S. SHNIDER1, D. JABAUDON2, J. SONG1, F. DING1, J. D. MACKLIS1;
1Stem Cell and Regenerative Biol. and Ctr. for Brain Sci., Harvard Univ., Cambridge, MA; 2Univ. of Geneva, Geneva, Switzerland

Vibhu Sahni, Harvard University

The corticospinal system controls performance of skilled and complex movements. For precise motor control, distinct corticospinal motor neurons (CSMN) extend axons to, and innervate, distinct target spinal cord segments – from rostral targets in the brainstem and cervical cord (controlling face and forelimb movements) to caudal targets in the thoracic and lumbar cord (controlling hindlimb movements). The molecular basis for this segmentally specific connectivity is unknown.
We identified specific CSMN subpopulations that exhibit striking axon targeting specificity during development. We identified that CSMN in rostrolateral sensorimotor cortex extend axons exclusively to subcerebral targets in the brainstem and cervical spinal cord (CSMNBC), and do not extend axons past these targets toward thoracic or lumbar cord. CSMNBC largely reside outside primary motor cortex (M1), comprise a significant subset of the total cortical projections to the cervical spinal cord, and exhibit distinct spinal connectivity from CSMN in M1 in the mature CNS. In complementary fashion, CSMN extending axons past the cervical cord toward thoracic and lumbar spinal segments (CSMNTL) reside exclusively in medial sensorimotor cortex, residing entirely within M1.
We isolated CSMNBC and CSMNTL during development, and identified differentially expressed genes between them. Using this approach, we identified that:
1. CSMN subpopulations are molecularly distinct from the earliest stages of development.
2. Using transgenic Cre reporter mouse lines, we find that these molecular controls prospectively identify developing CSMN subpopulations that eventually extend axons to bulbar-cervical versus thoraco-lumbar segments.
3. Using intersectional mouse genetics, we additionally find that CSMNTL extend exuberant collaterals into cervical spinal segments. This indicates that mechanisms controlling CSMN axon targeting versus axonal collateralization to specific spinal segments are independent of one another.
4. We identify that a subset of these controls direct CSMN axons to appropriate spinal levels – bulbar-cervical extension by CSMNBC and thoraco-lumbar extension by CSMNTL. These axon extension decisions occur prior to axonal collateralization, and therefore are independent of connectivity.
Together, these newly identified controls constitute new mechanisms directing CSMN axonal targeting. This work provides foundation for further investigation of mechanisms directing the development, regeneration, and evolution of precise corticospinal circuitry, and the roles of molecularly distinct CSMN subpopulations in voluntary motor control.

Disclosures
V.V. Sahni: None. S. Shnider: None. D. Jabaudon: None. J. Song: None. F. Ding: None. J.D. Macklis: None.
LINK: Society for Neuroscience

Grant Support
ALS Association
Grant Support
Travis Roy Foundation
Grant Support
Packard Center for ALS Research
Grant Support
Massachusetts Dept of Public Health

Vibhu Sahni

Posted in Chronic Spinal Cord Injury Research, Regenerative Medicine, Spinal Research, Stem Cell Research | Tagged , | Leave a comment

Novel induction of neural-ectoderm and differentiation of neural progenitors from human iPSCs using pressure

Authors: Z. PAPPALARDO1,2, L. CASSEREAU2, *B. A. ADAMS2, B. DOWNEY2, J. LIM2;
1San Francisco State Univ., San Francisco, CA; 2Xcell Biosci. Inc., San Francisco, CA

Induced pluripotent stem cells (iPSCs) can be used for autologous regenerative medicine to treat conditions such as spinal cord injuries and neuropathology-associated genetic disease. iPSCs can differentiate to neural progenitor cells (NPCs), a multipotent population that can give rise to all lineages of adult neural cells. However, a confounding limitation of neurons derived from iPSC-derived NPCs is that they are not genetically and functionally equivalent to adult neurons in vivo, rendering in vitro systems as sub-optimal surrogates. Furthermore, maturation of iPSC-derived neurons for regenerative medicine may improve clinical efficacy of neural cell transplants. Recent studies highlight the significance of micro-environmental factors such as hypoxia and mechanical force / pressure on stem cell maintenance and directed-differentiation to specific cell lineages, yet none have evaluated the combined contribution of these factors towards differentiation of iPSCs to NPCs and subsequent maturation of differentiated neurons. We demonstrate the biological impact of oxygen and atmospheric pressure on differentiation to NPCs from human iPSCs. Also, we explore how atmospheric pressure-mediated force can act with soluble factors to promote differentiation of NPCs to mature neurons. We used the AVATAR™, which allows tunable control of the microenvironment ex vivo, to allow precise control of physiologically-relevant levels of oxygen and pressure simultaneously. We demonstrate that combinatorial oxygen and pressure are significant drivers of NPC differentiation from iPSCs. We used settings for oxygen concentration (5% vs normoxia) and atmospheric pressure (2 PSI + atmospheric) during re-programming of fibroblasts to iPSCs and identified pressure-dependent increases in genes involved in re-modeling of the extra-cellular matrix and neural differentiation. We further show that in the absence of soluble differentiating factors, oxygen and pressure are sufficient to fully differentiate iPSCs to NPCs expressing PAX6, NES, and SOX2. When evaluating the effects of oxygen/pressure plus soluble factors for neural induction of iPSCs we see an increase in efficiency relative to a standard CO2 incubator workflow. We now are leveraging the differentiation potential of combinatorial oxygen and atmospheric pressure towards maturation of CNS neurons, astrocytes, and motor neurons. Our findings suggest that oxygen and pressure are important drivers of neural differentiation from human iPSCs, and that these factors have the potential to induce maturation of neurons such that they are better suited for translational studies in vitro and in the clinic.

Disclosures
Z. Pappalardo: A. Employment/Salary (full or part-time):; Xcell Biosciences Inc. L. Cassereau: A. Employment/Salary (full or part-time):; Xcell Biosciences Inc. B.A. Adams: A. Employment/Salary (full or part-time):; Xcell Biosciences Inc. E. Ownership Interest (stock, stock options, royalty, receipt of intellectual property rights/patent holder, excluding diversified mutual funds); Xcell Biosciences Inc. B. Downey: A. Employment/Salary (full or part-time):; Xcell Biosciences Inc. J. Lim: A. Employment/Salary (full or part-time):; Xcell Biosciences Inc. E. Ownership Interest (stock, stock options, royalty, receipt of intellectual property rights/patent holder, excluding diversified mutual funds); Xcell Biosciences Inc.

LINK: Society for Neuroscience

Grant Support
EDUC2-08391 CIRM bridges 2.0 to ZP

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Regenerative Medicine, Spinal Research, Stem Cell Research | Tagged , | 1 Comment

Differentiation and single cell RNA sequencing of V2a interneurons from human pluripotent stem cells

Authors
*J. BUTTS1, D. A. MCCREEDY2, J. A. MARTINEZ-VARGAS3, C. A. GIFFORD4, L. J. NOBLE-HAEUSSLEIN5, T. C. MCDEVITT4;
1Bioengineering, Gladstone Inst. of Cardiovasc. Dis., San Francisco, CA; 2Neurolog. Surgery, UCSF, San Francisco, CA; 3Univ. of California – Berkeley, Berkeley, CA; 4Gladstone Inst., San Francisco, CA; 5Dept. of Neurosurg and Physical Therapy and Rehabil. Sci., Univ. California, San Francisco, CA
Disclosures
J. Butts: None. D.A. McCreedy: None. J.A. Martinez-Vargas: None. C.A. Gifford: None. L.J. Noble-Haeusslein: None. T.C. McDevitt: None.

LINK: Society for Neuroscience

V2a interneurons (INs) are a critical population of neurons found in the hindbrain and spinal cord that are necessary for coordinated motor function, including control of breathing and locomotion. V2a INs span several spinal cord segments and relay excitatory information to adjacent INs and downstream motor neurons. While studies of murine V2a INs have provided critical early characterization of this population, there is no robust source of human V2a INs to phenotypically characterize this cell population in vitro as a potential therapy for human motor dysfunction. Therefore, we recently described a protocol to differentiate V2a INs, marked by the CHX10 transcription factor, from human pluripotent stem cells (hPSCs). Drawing inspiration from neural tube development, the critical signaling molecules retinoic acid (RA), Purmorphamine (Pur, a Shh agonist), and DAPT (a Notch inhibitor) were varied systematically until a CHX10+ population of approximately 30% was obtained with 100nM RA, 100nM Pur, and 1μM DAPT. After starting with human ESCs (H7), the protocol was reproduced in three additional hPSC lines (H1 ESCs, WTC and WTB induced PSCs), to yield CHX10 percentages between 25-50%. Expression of V2a IN lineage markers (CHX10, SOX14) was highly upregulated (~100-fold) when compared to a published motor neuron protocol. Single cell RNA sequencing was performed to identify the cell populations in the V2a IN differentiation. K-means clustering of twelve principle components revealed seven distinct cell populations including mature neurons, progenitor neurons, and glial cells. The cluster containing the majority of CHX10-expressing cells also expressed other markers of V2a interneurons (SOX21 and SHOX2), as well as genes associated with a glutamatergic phenotype (PCP4 and OAT). V2a cultures expressed a mature glutamatergic neuronal phenotypic (NeuN+ and VGlut2+) and demonstrated increased action potential frequency when cultured for up to 60 days. To determine if V2a interneuron cultures could integrate with the endogenous spinal cord, dissociated cultures were transplanted into T9 vertebrae of uninjured mice and resulted in survival and neurite extension greater than 5mm rostral and caudal to the transplantation site. Transplanted cells expressed the presynaptic maker synaptophysin on neurite terminals adjacent to host NeuN+ neurons, indicating integration with host circuitry. In summary, we have developed the first protocol to differentiate V2a INs from hPSCs that will allow for further characterization of novel phenotypic and electrophysiological properties of these cells.

Gladstone Article

Grant Support
CIRM Grant LA1-08015

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Regenerative Medicine, Spinal Research, Stem Cell Research | Tagged , | 1 Comment

Dr. Paul J. Reier presents at Working 2 Walk 2017

This Working 2 Walk 2017 video was taken in Miami Florida. Dr. Reier explained how electrical stimulation to activate silent neural circuits could be used to enhance spinal cord repair.

Dr. Reier’s research addresses spinal cord injury (SCI) and repair with emphasis on better definition of the targets for intervention and optimization of promising strategies such as the use of neural progenitors (i.e., neural stem or stem-like cells). Our therapeutic approaches and injury models are designed to address future bench-to-bedside translational issues with attention to experimental rigor, transparency, and independent replication. Our studies thus focus on gaining insights related to: (a) the contribution of gray matter pathology to post-SCI functional outcomes, (b) the development of a neuroengineering approach to reactivate a spinal circuit silenced by SCI, and (c) development of research proposals to use such neuroengineering approaches to promote more directed host-graft interactions following intraspinal transplantation of neural precursors.

Enhancement of Functionally Relevant Host-Graft Connectivity Following Neural Progenitor Cell Transplantation

Posted in Chronic Spinal Cord Injury Research, Rehabilitation, Spinal Research, Unite 2 Fight Paralysis, Working 2 Walk Science & Advocacy Symposium | Tagged , , , | Leave a comment

Partnership Hopes to Bring Breakthrough Epidural Stimulator Technologies to Millions

Inspired by the results of the first trial and the possibility of two very significant neuromodulation methods, the Foundation was motivated to accelerate its work. The prize of completing its mission and finding cures for spinal cord injury now seemed even more possible. The Foundation creatively turned to private business for help in bringing a commercially viable cure to the millions impacted by SCI. According to Wilderotter, The Foundation turned to Presidio Partners and jointly created a new entity, which formed NeuroRecovery Technologies (NRT) in November of 2016.

According to the Presidio Partners website, “NeuroRecovery Technologies is a new, cutting-edge medical technology company focused on the design and development of devices and applications to help restore function & movement in patients with paralysis. Our current technology evolved from collaborative research between The University of California Los Angeles, The California Institute of Technology, and The University of Louisville.

NeuroRecovery Technologies is dedicated to developing disease and injury specific devices to help restore optimal physiological function to damaged neural circuits and their target end points. Our goal is to commercialize and make readily available new technological advancements in medical devices, complemented by good clinical practices, which bring about the recovery of neuromotor and sensory function of the brain and spinal cord.”[1] SEC filings[2] show NRT was funded as the Reeve Foundation – Presidio Partners NRT, L.P. and formed in 2016. It is owned by the Foundation through a special purpose vehicle (SPV) that enables the Foundation to maintain its not-for-profit status. Initial funding was for $2.460 million yet Wilderotter said Reeve funding has increased to over $ 4million with a goal of $8 million by mid 2018.

http://www.boldbusiness.com/health/partnership-aims-to-end-spinal-cord-injury/

Posted in Chronic Spinal Cord Injury Research, Rehabilitation, Spinal Research | Leave a comment

Fortuna Fix Announces Series B Financing, Adding Amgen Ventures and Macnguyen Family Office as Shareholders

(Newswire.com) Press Release: November 8, 2017 Fortuna Fix

– Fortuna Fix (“Fortuna”), a private, clinical-stage Regenerative Medicine company is aiming to be the first to bring to the clinic a patient’s own neural stem cells (autologous) produced by direct reprogramming (“drNPCs”) to replace lost neuronal tissue in neurodegeneration and neurotrauma.

Fortuna announces today the closing of its USD 25 million Series B financing. The proceeds will enable the company to conduct Phase I/IIa clinical trials in Parkinson’s Disease and Spinal Cord Injury. Amgen Ventures and other new investors join existing shareholders, including Salamander Invest to support the development of Fortuna’s lead programs and its neuro-regenerative technology platforms. In addition to clinical development, the financing will enable further expansion of Fortuna’s automated robotic manufacturing capabilities.

“We are excited to welcome Amgen Ventures and our other investors to Fortuna and I would like to thank them for their strong support for the development of our ethical cell therapies and for their help in bringing our novel regenerative medicine solutions to patients suffering from neurotrauma and neurodegeneration,” says Jan-Eric Ahlfors, CEO and CSO of Fortuna.

Jan-Eric Ahlfors
Fortuna Fix

“With Fortuna’s technology platform, there finally exists a tremendous opportunity to deliver autologous drNPCs that can readily replace lost neurons, do not require immune suppression, are ethically sourced, efficacious and address some of the largest unmet medical needs by fixing the underlying pathology of cell loss to enable restoration of functionality in patients.”

Fortuna’s autologous drNPCs are expected to help regenerate neural tissue with the following major benefits to patients:

1. For the first time, patients suffering from neurotrauma or neurodegeneration will be able to be treated with their own neural stem cells providing functional integration without immunosuppression or ethical issues (the technology uses no fetal, embryonic-like, or other ethically challenging processes).
2. The manufacturing of autologous drNPCs is accomplished with a rapid, high throughput, and fully automated process, which does not involve genetic engineering, animal components, or staged pluripotency.

Fortuna’s second neuro-regenerative technology platform – Regeneration Matrix (RMx™) – will be developed as an off-the-shelf product to be used in acute settings to support regeneration and prevent secondary damage after neurotrauma. RMx™ is a unique and highly efficient bio-scaffold that promotes neural tissue regrowth that can also be used in combination with the drNPCs to help with grafting.

In conjunction with the investment by Amgen Ventures, Dr. John Dunlop (Ph.D), Amgen Vice President, Neuroscience Discovery Research, and Philip Tagari, Amgen Vice President, Therapeutic Discovery, will take the roles of Scientific Advisory Board member and Board observer at Fortuna, respectively.

Dr. Dunlop has been with Amgen since 2016 and is leading efforts focused on neurodegenerative diseases, migraine and analgesia. Previously he was VP and Head of the Neuroscience Innovative Medicine Unit at AstraZeneca, leading discovery and early development efforts. Prior to joining AstraZeneca, Dr. Dunlop was Executive Director in the Neuroscience Research Unit at Pfizer with responsibility for the preclinical portfolios in Neurology and Psychiatry. He joined Pfizer as part of the Wyeth integration and at Wyeth held roles as head of Psychiatry and Acting Head of Neuroscience. Trained as a neuropharmacologist, his current research interests include the role of proteostasis mechanisms, innate immunity and mitochondrial dysfunction in neurodegenerative diseases such as Alzheimer’s, Parkinson’s disease and ALS, and on the emerging genetics of brain disorders. He is a member of the Executive Scientific Advisory Board for the Michael J.Fox Foundation for Parkinson’s disease, a board member of Target ALS, and serves as a scientific advisor to the ALS Association, the frontotemporal dementia biomarkers SAB, the Weston Brain Institute of Canada and the National Institute for Neurological Disorders and Stroke for translational programs in neurological disorders.

Mr.Tagari has been with Amgen for close to 20 years and has amassed 25 years of research experience in the areas of neurobiology, hematology/oncology, metabolic disease, immunology & inflammation, cell and molecular biology, peptide chemistry, analytical chemistry & biochemistry, structural biology, pharmacokinetics, safety pharmacology, laboratory automation and information technologies, that have led to several important experimental and marketed therapies and over 65 peer-reviewed publications.

“This investment in Fortuna represents Amgen’s first foray into cellular regenerative research and underscores our commitment to advancing novel neuroscience research for serious brain diseases, such as Parkinson’s,” said Philip Tagari, Amgen Vice President, Therapeutic Discovery. “Regenerative medicine is one of the most exciting fields of healthcare today, and we are delighted to participate in the advancement of these
innovative solutions for patients suffering from severe neurodegenerative diseases and neurotrauma.”

About Amgen Ventures:
Amgen Ventures provides emerging biotechnology companies with financial and other resources to develop pioneering discoveries focused on human
therapeutics. Since 2004, Amgen Ventures has invested in biotechnology companies to advance promising medicines and technologies that could ultimately make a difference for patients suffering from serious illnesses. Leveraging Amgen’s industry leadership, deep knowledge, and longstanding expertise in biotechnology, Amgen Ventures’ investments are made in areas of strategic focus for the company to support innovation and generate
financial return.

About Macnguyen Family Office:
Curtis Macnguyen is founder and CIO of a Los Angeles based investment firm. His family office employs a private equity approach to execute a broad, opportunistic investment mandate in the private markets across industries, asset classes and capital structures.

About Salamander Invest:
Salamander Invest is a single purpose investment company established by Norwegian family offices and institutional investors to support the clinical
development and commercialization of Fortuna’s technology platforms for neuroregeneration. About Fortuna Fix Fortuna is a private, clinical-stage biotech company with a patented direct cell reprogramming technology platform (drNPC) and a proprietary bio-scaffolding technology (RMx™), for the treatment of neurodegenerative diseases and neurotrauma. The company is focused on its lead programs in Spinal Cord Injury and Parkinson’s disease with further development efforts in Stroke, Traumatic Brain Injury, Hearing Loss and ALS. The company has developed a proprietary, large-scale and fully automated GMP manufacturing system for production of autologous drNPCs.

Media contact
Dr. Masha Legris Stromme
Email: m.legris@fortunafix.com
www.fortunafix.com
Source: Fortuna Fix

Posted in Biomaterials, Chronic Spinal Cord Injury Research, Regenerative Medicine, Spinal Research, Stem Cell Research | Tagged ,

Targeting improvements in bladder function with epidural stimulation after human SCI

Abstract
Deficits in urological function after spinal cord injury (SCI) include neurogenic detrusor overactivity and uncoordinated bladder and external urethral sphincter contractions, resulting in inefficient emptying and high intravesical pressure. Urinary retention and an inability of the bladder to store urine under appropriately low pressures can lead to infection and ultimately impact renal health. Current therapeutic approaches aim to manage both the storage and voiding phases of bladder function and include intermittent catheterization, pharmacologic and surgical interventions, as well as urethral stents. While most of these strategies are necessary for urological maintenance post-injury they oftentimes are associated with dose-limiting side effects and therefore remain inadequate. Neuromodulation has also been implemented in various formats as a promising alternative treatment for neurogenic bladder in an effort to regain control of function after SCI. Thus, this study investigated bladder outcomes in AIS grade A and B subjects receiving spinal cord epidural stimulation (scES) at L1-S1 spinal levels in combination with locomotor and/or stand training by our research team at the University of Louisville Human Locomotion Research Center. Urodynamic assessments were performed at pre- and post-training time-points and cystometrograms were captured with and without the use of scES. In addition, specific configurations and parameters optimal for continence and micturition were identified in several subjects during filling cystometry. We found that while locomotor training resulted in improvements in bladder capacity and voiding efficiency, the use of scES further enhanced these parameters and in a frequency-dependent manner. Importantly, as capacity increased, bladder pressures continued to remain low, indicating better compliance. Overall, scES may help contribute to an improvement in quality of life by providing a means of extending the time to catheterization under safe pressures and restoring efficient bladder emptying, ultimately preserving lower and upper urinary tract health.

Authors
*C. HUBSCHER1, A. HERRITY2, L. MONTGOMERY1, A. WILLHITE2, C. ANGELI2, S. HARKEMA2;
1Dept Anatom. Sci. & Neuro, Univ. Louisville Sch. Med., Louisville, KY; 2KSCIRC, Frazier Rehab Inst., Louisville, KY
Disclosures
C. Hubscher: None. A. Herrity: None. L. Montgomery: None. A. Willhite: None. C. Angeli: None. S. Harkema: None.

LINK: Session 323 – Spinal Cord Injury Models and Mechanisms

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Rehabilitation, Spinal Research | 2 Comments

Cellular mechanisms influencing corticospinal and sensory axonal regeneration into neural stem cell grafts after SCI

Abstract
Injured corticospinal tract axons regenerate robustly into caudalized neural progenitor cell (NPC) grafts and form functional synaptic connections with graft-derived neurons. However, the developmental fate of grafted NPCs, and whether those differentiated graft-derived neural subtypes might influence the regeneration of host axonal projections, remain unexplored. We demonstrate that upon maturation, embryonic spinal cord NPCs grafted into the injured, adult spinal cord contain clusters of dorsal spinal cord sensory interneurons that are potent zones of exclusion for regenerating corticospinal axons, but receive dense innervation by host CGRP+ sensory axons, reflecting the normal topographical projection patterns of these axons into distinct spinal cord laminae. Notably, these sensory neuron clusters form curved, layered structures populated by neuronal subtypes normally present in superficial dorsal horn laminae I-III, revealing the endogenous self-assembly of spinal cord dorsal horn-like structures within dissociated NPC grafts. These findings reveal a previously unknown barrier to corticospinal axon regeneration into otherwise highly permissive neural grafts, and more generally that axons of adult central and peripheral neurons reinnervate topographically appropriate regions of newly-born neurons after spinal cord injury. Moreover, these findings demonstrate the ability of transplanted dissociated embryonic NPCs to recapitulate assembly of adult spinal cord cytoarchitecture following engraftment into the injured, adult CNS.

Authors
*J. N. DULIN1, A. F. ADLER1, H. KUMAMARU1, M. H. TUSZYNSKI1,2;
1Dept. of Neurosciences, UCSD, La Jolla, CA; 2Veterans Affairs Med. Ctr., San Diego, CA
Disclosures
J.N. Dulin: None. A.F. Adler: None. H. Kumamaru: None. M.H. Tuszynski: None.

LINKS: Session 522 – Regenerative Approaches: Spinal Cord Injury

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Regenerative Medicine, Rehabilitation, Spinal Research, Stem Cell Research

Motor recovery after activity-based training with spinal cord epidural stimulation in a chronic motor complete paraplegic

Enrico Recj PhD

The prognosis for recovery of motor function in motor complete spinal cord injured (SCI) individuals is poor. Our research team has demonstrated that lumborsacral spinal cord epidural stimulation (scES) and activity-based training can progressively promote the recovery of volitional leg movements and standing in individuals with chronic clinically complete SCI. However, scES was required to perform these motor tasks. Herein, we show the progressive recovery of voluntary leg movement and standing without scES in an individual with chronic, motor complete SCI throughout 3.7 years of activity based interventions utilizing scES configurations customized for the different motor tasks that were specifically trained (standing, stepping, volitional leg movement). In particular, this report details the ongoing neural adaptations that allowed a functional progression from no volitional muscle activation to a refined, task-specific activation pattern and movement generation during volitional attempts without scES. Similarly, we observed the re-emergence of muscle activation patterns suffcient for standing with independent knee and hip extension. These findings highlight the recovery potential of the human nervous system after chronic clinically motor complete SCI.

By: Enrico Rejc, Claudia A. Angeli, Darryn Atkinson, Susan J. Harkema

Read the Full Open Article at Nature Scientific Reports HERE
Published online October 26, 2017

UL Press Conference Video:

WLKY News HERE:

Newsweek Article:

Science Daily Article:

Medical Xpress News Article HERE

Posted in Chronic Spinal Cord Injury Research, Spinal Research | Tagged , , , ,