How paralyzed people are learning to walk

How paralyzed people are learning to walk | Susan Harkema | TEDxManhattanBeach

Until now, it was believed that paralysis resulting from spinal cord injury was irreversible. In her provocative talk, Susan Harkema shares breakthrough research showing amazing functionality of the spinal cord, giving people with paralysis new reason for hope. Medical Disruptor This talk was given at a TEDx event using the TED conference format but independently organized by a local community.

Posted in Neuromodulation, Rehabilitation, spinal cord injury research | Tagged | 1 Comment

Edonerpic maleate boosts motor function recovery from spinal cord injury

Authors: M. SATO, S. JITSUKI, H. MASUYAMA, H. MURATA, T. YAMAMOTO, T. TAKAHASHI

Lab Abstract:

Spinal cord injury (SCI) is a miserable neurological condition that often causes permanent sensory, motor, and bladder-bowel dysfunction. Despite the needs of treatments, clinical options for treatments is limited. Neuronal plasticity is a mechanism underlying the recovery process of motor function after the injury of central nervous systems, and the experience-dependent synaptic AMPA (α-amino-3-hydoroxy-5methyl-4-isoxazole-propionic-acid) receptor (AMPAR) delivery is a molecular and cellular mechanism of neural plasticity. We recently found that a small compound, edonerpic maleate (also known as T-817MA), facilitated experience-driven synaptic glutamate AMPA receptor delivery and resulted in the acceleration of motor function recovery after brain damage in mice and monkeys in a training-dependent manner (Abe et al. Science 2018). Here, we report that edonerpic maleate also facilitates the motor function recovery after spinal cord injury in rats.

*M. SATO1, S. JITSUKI1, H. MASUYAMA2, H. MURATA1, T. YAMAMOTO1, T. TAKAHASHI11Yokohama City Univ., Yokohama-Shi, Japan; 2Toyama Chem. Co., Tokyo, Japan. Edonerpic maleate boosts motor function recovery from spinal cord injury. Program No. 298.14. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

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Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, spinal cord injury research | 2 Comments

Opinion: Ethical Challenges in Using iPS Cells to Treat Paralysis

Uncertainties about the cells’ risk profiles and the potential for hyping unproven therapies mean scientists and the media must tread carefully.

On February 18, 2019, The Asahi Shimbun reported, “Ministry [of Health, Labor and Welfare in Japan] OKs 1st iPS [induced pluripotent stem] cell therapy for spinal cord injuries.” This announcement disseminated at a press conference has been viewed as an exciting clinical trial on the use of stem cells to treat spinal cord injury. However, caution is warranted here, for at least three reasons: the uncertainty of the stem cell type to be used in their clinical trial, the safety of transplanting stem cells into humans, and the responsibility of scientists and the press to communicate clearly the benefits and risks of the stem cell treatments, especially to desperate patients who would seek such unproven treatments.

Read the Full Article at The Scientist:

John D. Loike, a professor of biology at Touro College and University Systems, writes a regular column on bioethics for The Scientist. Martin Grumet is a professor of Cell Biology & Neuroscience, associate director of WM Keck Center for Collaborative Neuroscience, and director of the Stem Cell Research Center at Rutgers.

Posted in Chronic Spinal Cord Injury Research, spinal cord injury research, Stem Cell Research

Mechanisms of noradrenergic modulation of synaptic transmission and neuronal excitability in ventral horn neurons of the rat spinal cord

Authors: H. SHOJI, M. OHASHI, T. HIRANO, K. WATANABE, N. ENDO, T. KOHNO

Lab Abstract:
“Noradrenaline (NA) modulates the spinal motor networks for locomotion and facilitates neuroplasticity, both of which are important for neural recovery in the subacute and chronic phases of spinal cord injury. However, neither the effects of NA on synaptic transmission and neuronal excitability in spinal ventral horn (VH) neurons nor their mechanisms are well characterized. To gain insight into NA regulation of VH neuronal activity, we used a whole-cell patch-clamp approach in neonatal rats (7-15 day old). NA facilitated both excitatory and inhibitory synaptic transmissions through the activation of somatic adrenoceptors in the excitatory and inhibitory interneurons, respectively. In current-clamp recordings, NA depolarized resting membrane potentials in VH neurons, indicating that NA enhanced excitability of these neurons. In voltage-clamp recordings at -70 mV, the enhancement of excitatory synaptic transmission was induced by the activation of α1- and β-adrenoceptors. NA induced an inward current, also mediated by the activation of α1- and β-adrenoceptors. Activation of α1-adrenoceptors after spinal cord injury has been reported to be associated with muscle spasm or spasticity, which interrupt fluid motion in the extremities. Therefore, our findings indicate that the activation of β-adrenoceptors may instead be used as the foundation of one of the therapeutic targets to activate neural networks in the spinal VH without causing muscle spasm or spasticity and ultimately, improve motor function after spinal cord injury.”

Abstract Citation
H. SHOJI1, M. OHASHI1, T. HIRANO1, K. WATANABE1, N. ENDO1, *T. KOHNO2;
1Orthopedic Surgery, Niigata Univ. Grad. Sch. of Med. and Dent. Sci., Niigata city, Japan; 2Dept. of Anesthesiol., Tohoku Med. and Pharmaceut. Univ., Sendai-Shi, Japan. Mechanisms of noradrenergic modulation of synaptic transmission and neuronal excitability in ventral horn neurons of the rat spinal cord. Program No. 203.22. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Regenerative Medicine, spinal cord injury research | Tagged

Marquette receives $500,000 for research from the Bryon Riesch Foundation

The Bryon Riesch Paralysis Foundation pledged Feb. 15 to donate $500,000 to Marquette’s College of Health Sciences to fund research, particularly that of Murray Blackmore, an associate professor of biomedical sciences.

Dr. Murray Blackmore Marquette University

Blackmore’s lab studies spinal cord injuries, but more specifically studies gene therapy, grafts of stem cells that go into the spinal cord and regrowing axons, which allow the brain to communicate with the spinal cord.

Read the Full Article at Marquette Wire.

4 Chapters that explain the beginning

Posted in Chronic Spinal Cord Injury Research, Gene Therapy, Regenerative Medicine, spinal cord injury research | Tagged , ,

NERVGEN PHARMA COMPLETES $10 MILLION INITIAL PUBLIC OFFERING

Vancouver, Canada. March 13, 2019 – NervGen Pharma Corp. (“NervGen” or the “Company”), a regenerative medicine company dedicated to creating innovative solutions for the treatment of nerve damage, today announced that it has completed its initial public offering (“IPO”) of its common shares and listing as a Tier 2 company on the TSX Venture Exchange (“TSX-V”). The IPO consisted of the issuance of 10,000,000 common shares of the Company at a price of $1.00 per share for gross proceeds of $10,000,000. NervGen’s common shares are expected to commence trading on the TSX-V under the symbol “NGEN” on Friday, March 15, 2019.

Read the full article at this NervGen LINK

BioEnterprise Article March 18, 2019

Posted in Ligand, Regenerative Medicine, spinal cord injury research | Tagged , ,

Acteoside Improves Muscle Atrophy and Motor Function by Inducing New Myokine Secretion in Chronic Spinal Cord Injury

Authors: Kodani A1Kikuchi T1Tohda C1. Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Toyama, Japan

Chihiro Tohda, PhD

Lab Abstract:

Chronic spinal cord injury (SCI) is difficult to cure, even by several approaches effective at the acute or subacute phase. We focused on skeletal muscle atrophy as a detrimental factor in chronic SCI and explored drugs that protect against muscle atrophy and activate secretion of axonal growth factors from skeletal muscle. We found that acteoside induced the secretion of axonal growth factors from skeletal muscle cells and proliferation of these cells. Intramuscular injection of acteoside in mice with chronic SCI recovered skeletal muscle weight reduction and motor function impairment. We also identified pyruvate kinase isoform M2 (PKM2) as a secreted factor from skeletal muscle cells, stimulated by acteoside. Extracellular PKM2 enhanced proliferation of skeletal muscle cells and axonal growth in cultured neurons. Further, we showed that PKM2 might cross the blood-brain barrier. These results indicate that effects of acteoside on chronic SCI might be mediated by PKM2 secretion from skeletal muscles. This study proposes that the candidate drug acteoside and a new myokine, PKM2, could be used for the treatment of chronic SCI.

Citation:  2019 Jan 10. doi: 10.1089/neu.2018.6000. [Epub ahead of print]

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, spinal cord injury research | Tagged , , , , | 2 Comments

Restoring function after severe spinal cord injury through bioluminescence-driven optogenetic stimulation of spinal circuitry

Authors:
E. D. PETERSEN, A. PAL, J. ZENCHAK, E. D. SHARKEY, L. SHAFAU, A. PENA, M. PRAKASH, U. HOCHGESCHWENDER;
Central Michigan Univ., Mount Pleasant, MI

Eric D. Petersen, Graduate Student , Central Michigan University

Lab Team Abstract:
The ability to manipulate specific neuronal populations of the spinal cord following spinal cord injury (SCI) could potentially prove highly beneficial for rehabilitation in patients through maintaining and strengthening still existing neuronal connections and/or facilitating the formation of new connections. A non-invasive and highly specific approach to neuronal stimulation is bioluminescent-optogenetics, where genetically expressed light emitting luciferases are tethered to light sensitive channelrhodopsins (luminopsins, LMO); neurons are activated by the addition of the luciferase substrate coelenterazine (CTZ). This approach takes advantage of utilizing ion channels for current conduction while activating the channels through application of a small chemical compound, thus allowing non-invasive stimulation and recruitment of all targeted neurons. Rats were transduced in the lumbar spinal cord with AAV2/9 expressing the excitatory LMO3 under control of the synapsin or the Hb9 promoter. A day after contusion injury of the thoracic spine, rats received either CTZ or vehicle every other day for 2 weeks. We found activation of either interneuron or motor neuron populations below the level of injury to significantly improve locomotor recovery. This is the first example of non-invasive activation of an optogenetic component as a potential therapy following spinal cord injury. We are utilizing morphological and histological methods to identify mechanisms underlying improvements in locomotion. The findings will provide a foundation for a rational approach to spinal cord injury, thereby advancing approaches for functional recovery after SCI in the preclinical arena.

Abstract Citation
*E. D. PETERSEN, A. PAL, J. ZENCHAK, E. D. SHARKEY, L. SHAFAU, A. PENA, M. PRAKASH, U. HOCHGESCHWENDER;
Central Michigan Univ., Mount Pleasant, MI. Restoring function after severe spinal cord injury through bioluminescence-driven optogenetic stimulation of spinal circuitry. Program No. 138.10. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

Grant Support: NIH Grant MH101525, NIH Grant EY026427, NIH Grant NS099709
NSF Grant 1464686, NSF Grant 1707352, W.M. Keck Foundation

Posted in Biomaterials, Chronic Spinal Cord Injury Research, Neuromodulation, Neuroscience Abstracts, Rehabilitation, spinal cord injury research | Tagged , ,

Repositioning Flubendazole for Spinal Cord Injury

Authors: Yu CG1Bondada V2Ghoshal S3Singh R4Pistilli CK5Dayaram K6Iqbal H7Sands M8Davis K9Bondada S10Geddes JW11   University of Kentucky Spinal Cord and Brain Injury Research Center

Lab Abstract

We previously reported the serendipitous observation that Fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. In the present study we evaluated post-injury administration of a closely related, human anthelmintic drug, Flubendazole, using a rat spinal cord contusion injury model. Flubendazole, administered IP, 5 or 10 mg/kg day, beginning 3 hrs postinjury and daily thereafter for 2 or 4 weeks, resulted in improved locomotor function after contusion SCI compared to vehicle-treated controls. Histological analysis of spinal cord sections showed that such treatment with Flubendazole also reduced lesion volume, improved total tissue sparing, white matter sparing, and gray matter sparing. Flubendazole inhibited the activation of GFAP, suppressed cyclin B1 expression and Bruton’s tyrosine kinase activation, markers of B cell proliferation and inflammation, and reduced B cell autoimmune response. Together, these results suggest the use of the benzimidazole anthelmintic Flubendazole as a potential therapeutic for spinal cord injury.

 2019 Feb 12. doi: 10.1089/neu.2018.6160. [Epub ahead of print]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048737/2015 Jan 3.

 

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, spinal cord injury research | Tagged , , , ,

Regenerative metabolic signaling after nerve and spinal injury

Authors:
Elisabeth SERGER, G. KONG, I. PALMISANO, E. MCLACHLAN, S. DI GIOVANNI

Elisabeth Serger, PhD Student in the Prof. Simone Di Giovanni Lab

Lab Abstract:
Mammalian axonal regeneration is limited in the injured peripheral nervous system (PNS) occur and it fails in the central nervous system (CNS) such as after a spinal cord injury (SCI), strongly contributing to unsuccessful functional recovery. While we have been gaining knowledge in regenerative neuronal signaling pathways, the role of metabolic signaling remains rather elusive. Here, we hypothesize that injury as well as metabolism related signaling pathways might converge to regulate the axonal regenerative ability of sensory dorsal root ganglia (DRG) neurons. We performed high throughput unbiased studies investigating changes in metabolism and cell signaling to identify key regulatory mechanisms for the success of sensory axonal regrowth after injury. Currently, we are investigating the mechanisms underpinning metabolic signaling dependent regenerative phenotype. We next intend to manipulate the identified key pathways by gene therapy and/or pharmacologically to enhance the regeneration program. This will ultimately offer a new pathway to clinical translation for nerve repair after injury.

Grant Support: ISRT, Nathalie Rose Barr Studentship

Abstract Citation
*E. SERGER1, G. KONG2, I. PALMISANO1, E. MCLACHLAN1, S. DI GIOVANNI1;
1Imperial Col. London, London, United Kingdom; 2Univ. of Tuebingen, Tuebingen, Germany. Regenerative metabolic signaling after nerve and spinal injury. Program No. 213.17. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Regenerative Medicine, spinal cord injury research | Tagged ,