17th International Symposium on Neural Regeneration

Asilomar

The ISNR is a forum for the presentation and discussion of important research progress, insights and controversies important to advancing the understanding of injury responses and potential therapeutics targeting both peripheral nerve and central nervous system injuries. This year marks the 17th bi-annual meeting and the last time that we will be holding ISNR at the Asilomar conference grounds. I know that this is a meeting that many of you look forward to and I hope to see you again for this year’s meeting.

If you have already registered, thank you. If not, then please register and spread the word to your colleagues. Also, encourage your students and trainees to register. This is a perfect meeting for them!

The ISNR meeting will take place November 27-December 1, 2017 at the Asilomar Conference Grounds in Pacific Grove, CA.

Please visit http://theisnr.org/ to see this years agenda and to register.

Phillip Popovich, Ph.D., Director
International Symposium on Neural Regeneration
694 Biomedical Research Tower
460 W. 12th Ave
Columbus, Ohio 43210 USA
Phone: 614-688-8576 | Email: ISNR@osumc.edu

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Spinal Research | Tagged | Leave a comment

Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury

Marc A. DePaul

Eight weeks post contusive spinal cord injury, we built a peripheral nerve graft bridge (PNG) through the cystic cavity and treated the graft/host interface with acidic fibroblast growth factor (aFGF) and chondroitinase ABC (ChABC). This combinatorial strategy remarkably enhanced integration between host astrocytes and graft Schwann cells, allowing for robust growth, especially of catecholaminergic axons, through the graft and back into the distal spinal cord. In the absence of aFGF+ChABC fewer catecholaminergic axons entered the graft, no axons exited, and Schwann cells and astrocytes failed to integrate. In sharp contrast with the acutely bridge-repaired cord, in the chronically repaired cord only low levels of serotonergic axons regenerated into the graft, with no evidence of re-entry back into the spinal cord. The failure of axons to regenerate was strongly correlated with a dramatic increase of SOCS3 expression. While regeneration was more limited overall than at acute stages, our combinatorial strategy in the chronically injured animals prevented a decline in locomotor behavior and bladder physiology outcomes associated with an invasive repair strategy. These results indicate that PNG+aFGF+ChABC treatment of the chronically contused spinal cord can provide a permissive substrate for the regeneration of certain neuronal populations that retain a growth potential over time, and lead to functional improvements.

Authors: Marc A. DePaul, Ching-Yi Lin, Jerry Silver, Yu-Shang Lee

See the Full Publication at Nature Scientific Reports: LINK

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

Gait Rehabilitation with a Neurologically Controlled Exoskeleton

Gait Rehabilitation with a Neurologically Controlled Exoskeleton
Ziadee Cambier, PT, MSPT, DPT

Ziadee Cambier Physical Therapist Swedish Medical Center


Seattle Science Foundation is a non-profit organization dedicated to the international collaboration among physicians, scientists, technologists, engineers and educators. The Foundation’s training facilities and extensive internet connectivity have been designed to foster improvements in health care through professional medical education, training, creative dialogue and innovation.

http://www.seattlesciencefoundation.org

NOTE: All archived recorded lectures are available for informational purposes only and are only eligible for self-claimed Category II credit. They are not intended to serve as, or be the basis of a medical opinion, diagnosis, prognosis, or treatment for any particular patient.

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

Nanoparticles limit damage in spinal cord injury

Injection after an injury reduces inflammation and scarring

Credit: CC0 Public Domain

By Marla Paul

After a spinal cord injury, a significant amount of secondary nerve damage is caused by inflammation and internal scarring that inhibits the ability of the nervous system to repair itself. A biodegradable nanoparticle injected after a spinal cord trauma prevented the inflammation and internal scarring that inhibits the repair process, reports a new Northwestern Medicine study.

As a result, mice with a spinal cord injury receiving the nanoparticle injection were able to walk better after the injury than those that didn’t receive it. The treatment could potentially limit secondary damage to the spinal cord in humans after an injury, if administered a few hours after the accident in an emergency room or by paramedics in an ambulance. “It’s not a cure. There is still the original damage, but we were able to prevent the secondary damage,” said co-senior author Dr. Jack Kessler, a professor of neurology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neurologist. “It’s an exciting potential treatment. We really believe this is something we’ll be able to take to the clinic.”

Further studies would need to confirm the safety of the injected nanoparticle, Kessler said, but he noted scientists haven’t seen any signs of toxicity so far. The nanoparticles work by binding to the cells that cause the inflammation — inflammatory monocytes — and diverting them to the spleen. The particles are made of poly(lactic-co-glycolic) acid, a biocompatible substance already approved by the Food and Drug Administration (FDA) for use in re-absorbable sutures. Developed in the lab of Northwestern scientist Stephen Miller, the particles also are FDA approved as an investigational drug for a new clinical trial in celiac disease. “The study results suggest nanoparticle infusion could offer a novel and practical potential treatment for human spinal cord injury, a condition for which there are currently no effective treatments,” said Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Feinberg.

“The new treatment is unusual because it is potentially immediately translatable to human beings,” Kessler said. “All we have to do is literally inject these beads into the blood stream. It doesn’t require surgery or any fancy intervention.” The tiny beads also are very stable and can be kept in a syringe, Kessler noted. “An emergency medical technician at the site of an accident or somebody in an emergency room when someone is brought in can give this injection immediately,” he said.

The nanoparticle technology is being developed commercially by Cour Pharmaceuticals Development Co., which is working with Miller to bring this new approach to patients. Miller is a co-founder of Cour and a member of the scientific advisory board.

The study was published in Neurobiology of Disease on August 24.

Miller also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Northwestern coauthors include Su Ji Jeong, John G. Cooper, Igal Ifergan, Tammy L. McGuire, Dan Xu, Zoe Hunter, Sripadh Sharma and Derrick McCarthy.

This research was supported by grants EB013198 from the National Institute of Biomedical Imaging and Bioengineering and NS026543 and F30NS093811 from National Institute of Neurological Disorders and Stroke, all of the National Institutes of Health.

Northwester Now News Full Article LINK
Science Direct LINK
Medical Express Article LINK

Posted in Neuroscience Abstracts, Regenerative Medicine, Spinal Research | Tagged , | Leave a comment

It’s Not a Rat’s Race for Human Stem Cells Grafted to Repair Spinal Cord Injuries

By Scott LaFee
Lengthy study finds that implanted neural stem cells grow slow and steady, and success needs to be measured accordingly

Paul Lu PhD Associate Researcher

More than one-and-a-half years after implantation, researchers at University of California San Diego School of Medicine and the San Diego Veterans Administration Medical Center report that human neural stem cells (NSCs) grafted into spinal cord injuries in laboratory rats displayed continued growth and maturity, with functional recovery beginning one year after grafting.

The findings are published in the September issue of the Journal of Clinical Investigation. Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

“The NSCs retained an intrinsic human rate of maturation despite being placed in a traumatic rodent environment,” said Paul Lu, PhD, associate professor of neurosciences and lead author of the study. “That’s a finding of great importance in planning for human clinical trials.”

Neural stem cells differentiate into neurons and glia or support cells. Researchers like Lu and colleague, Mark Tuszynski, MD, PhD, professor of neuroscience and director of the UC San Diego Translational Neuroscience Institute, have explored their potential as a sort of patch and remedy for spinal cord injuries, implanting NSCs derived from induced pluripotent stem cells into animal models of spinal cord injuries to repair damage. In previously published animal studies, Lu and Tuszynski have shown NSCs can survive implantation and make new connections, even beginning to restore limited physical function, such as foot movement, that had been lost to paralyzing injury.

But major questions remained: At what rate do the NSCs mature? And for how long? Rat biology works at a much faster pace than human. The gestational period for a human is 280 days; for a rat, it’s 21. The brain of a 2- or 3-year-old human child is comparable in body/brain weight ratios to a 20-day-old rat. It was possible that human NSCs in animal models would not accurately reflect functioning in future human patients.

“Most NSC grafting studies have been short-term, measuring survival times in weeks to a few months,” said Tuszynski. “That’s not enough time to fully measure the growth and maturation rate of human NSCs or what changes might occur farther out from the original grafting. These are important considerations, not just for the basic science of stem cell biology, but for the practical design of translational human trials using NSCs for spinal cord injuries. We need to better understand the long-term nature and time course so that we can accurately assess results and success.”

See the full article at UC San Diego Health Newsroom LINK

See related commentary: Patient Pays In Spinal Cord Injury

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

It’s On! U2FP Working 2 Walk 2017 and SCI Curecast Episode 11

Plan to join us in Miami for our 12th annual Working 2 Walk Symposium. The conference is a unique opportunity for spinal cord injury advocates, scientists, clinicians, and investors to meet and share the latest news & strategies, and form partnerships that will accelerate progress toward curative therapies.

Working 2 Walk Symposium Registration
October 13-14, 2017 – Miami, Florida

Register HERE

Working 2 Walk 2017 Agenda LINK

Working 2 Walk Speaker List HERE

Venue Lodging LINK

Kate and Matthew talk with Donna Sullivan, U2FP’s Special Projects Director and Chris Powell, U2FP’s Research Consultant. We talk about their stories of becoming engaged with SCI advocacy after their son’s were injured and how that weaves its way into U2FP’s Scientific Advisory Board, the Spinal Cord Research and Advocacy Blog and our Working 2 Walk Science and Advocacy Symposium (this year in Miami along with our Title Sponsor the Miami Project to Cure Paralysis on Oct. 13th and 14th). Take a listen at the Podcast LINK.

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

InVivo Therapeutics restructures and suspends chronic SCI stem cell and gene therapy research programs

CAMBRIDGE, Mass. (August 28, 2017) – InVivo Therapeutics Holdings Corp. (NVIV) today announced that it is executing a strategic restructuring in order to focus on The INSPIRE Study: InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold™ for Safety and Neurologic Recovery in Subjects with Complete Thoracic AIS A Spinal Cord Injury The strategic restructuring will allow the company to concentrate its efforts on reopening patient enrollment for INSPIRE, completing INSPIRE, and filing a Humanitarian Device Exemption (HDE) submission for the Neuro-Spinal Scaffold. The INSPIRE Study is designed to demonstrate the safety and probable benefit of the Neuro-Spinal Scaffold in patients with complete thoracic spinal cord injury, and currently has 16 patients in follow-up.

As part of the decision to focus exclusively on INSPIRE, the company also has announced the suspension of its chronic SCI stem cell and gene therapy research programs and a halt in enrollment into its Canadian cervical study of the Neuro-Spinal Scaffold. The company is evaluating strategic options for allowing the cell and gene therapy programs to move forward outside of the company and plans to restart the cervical study once the FDA approves a protocol that allows for enrollment in the United States.

In conjunction with the corporate restructuring, the company is undergoing a reduction in force (RIF), in which it is eliminating 13 positions, or approximately 39% of its workforce. The RIF, the recent update to the INSPIRE timeline, the suspension of the chronic SCI programs, and the halt to the cervical study together are projected to result in 2018 operating expense savings of approximately $7.3 million and to reduce 2018 cash burn from approximately $2.0 million per month to approximately $1.5 million per month.

“I feel confident that going forward, we have aligned our operational efforts and financial resources to fully support our core goal of bringing the Neuro-Spinal Scaffold to market. We continue to work with the FDA as expeditiously as possible with the goal of reopening enrollment in INSPIRE, and we look forward to completing the study and submitting our HDE application,” InVivo’s CEO and Chairman Mark Perrin said.

InVivo Article LINK

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

Pretreatment May Unlock the Regenerative Potential of Neural Stem Cells in Chronic Spinal Cord Injury

Written by 

Dr. Michael Fehlings University of Toronto

Michael G Fehlings, MD, PhD, spoke with Spine Universe about the study outcomes and potential clinical implications for patients with chronic spinal cord injury.

Chronic injury of the spinal cord results in the formation of a harsh injury microenvironment that is inhibitory to neural repair and regeneration; this is seen particularly with the creation of the glial scar formed by astrocytes surrounding the site of injury, explained senior author Michael G. Fehlings, MD, PhD, Professor of Neurosurgery and Co-Director of the Spine Program at the University of Toronto in Ontario, Canada. As part of the glial scarring process, inhibitory chondroitin sulfate proteoglycans (CSPGs) are deposited into the extracellular matrix, reducing the ability of axons to regenerate and repair following transplantation with exogenous NSCs Dr. Fehlings and colleagues noted in their paper.

“While stem cells show considerable promise as a potential therapeutic option for spinal cord injury, NSCs alone are not sufficient to enable repair and regeneration of the injured spinal cord unless one deals with these critical impediments to regeneration,” Dr. Fehlings told SpineUniverse.

“In this study, we showed that if we pre-treated the chronically injured spinal cord with an enzyme called ChABC, which degrades CSPGs in the extracellular matrix of the glial scar, it unlocks the potential for plasticity of the chronically injured spinal cord,” Dr. Fehlings explained.

See the full article at SpineUniverse

H. Suzuki H, Ahuja CS, Salewski RP, et al. Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury. PLoS One. 2017;12(8):e0182339.

Findings Point to Possible Major Therapeutic Intervention for Chronic Spinal Cord Injuries Via Stem Cell Injections Article
Lead author Ivan Cheng, MD, and Michael G. Fehlings, MD, PhD, comment

Cheng I, Githens M, Smith RL, et al. Local versus distal transplantation of human neural stem cells following chronic spinal cord injury. Spine J. 2016;16(6):764-769.

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

Regulateable Chondroitinase ABC gene therapy as a treatment for spinal cord injury

Emily Burnside

Following spinal cord injury the extracellular matrix undergoes significant remodeling. Scar formation is associated with upregulation of molecules known to be inhibitory to neural plasticity and recovery of function, including chondroitin sulphate proteoglycans (CSPGs). Enzymatic removal of CSPG glycosaminoglycan chains by the bacterial protein Chondroitinase ABC (ChABC) renders the matrix more permissive to recovery, however this is curtailed by rapidly diminishing enzyme activity. We have previously demonstrated that gene therapy using a modified ChABC gene compatible with expression and secretion by mammalian host cells confers sustained and long-term delivery of ChABC to the injured spinal cord following a single administration. This treatment resulted in dramatic reduction in pathology and significant improvements in functional recovery following clinically relevant spinal contusion injury at both thoracic and cervical levels in adult rats. We now use novel immune-evasive vectors to enable regulatable gene therapy to exert greater control over ChABC expression, where ability to switch off delivery of ChABC greatly improves safety of the treatment. Using this system, doxycycline administration results in high expression of the ChABC gene and extensive functional enzymatic removal of inhibitory components present in the extracellular matrix. We also show this is accompanied by pro-reparative changes in inflammatory markers. We aim to utilise this system to manipulate timing and duration of ChABC delivery to adult rats which have received a clinically-relevant contusion injury to the cervical spinal cord and investigate its efficacy in promoting functional recovery. This represents both an experimental tool to optimise and control ChABC delivery to understand the role of timing in ChABC treatment, and a step towards clinical feasibility of ChABC gene therapy.

Authors
*E. R. BURNSIDE1, F. DE WINTER2, A. DIDANGELOS1, N. D. JAMES1, K. BARTUS1, E. M. MUIR3, J. VERHAAGEN2, E. J. BRADBURY1;
1King’s Col. London, London, United Kingdom; 2Netherlands Inst. for Neurosci., Amsterdam, Netherlands; 3Univ. of Cambridge, Cambridge, United Kingdom
Disclosures
E.R. Burnside: None. F. de Winter: None. A. Didangelos: None. N.D. James: None. K. Bartus: None. E.M. Muir: None. J. Verhaagen: None. E.J. Bradbury: None.

LINK: Session 323 – Spinal Cord Injury Models and Mechanisms

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

Miracle chemical ‘cocktail’ could cure spinal cord damage

By Stephen Beech, SWNS

A chemical “cocktail” could restore movement for people crippled after suffering spinal cord injuries, suggests new research.

Scientists say the mixture of three molecules could potentially be given therapeutically to patients to aid in their recovery after serious injury.

After spinal cord injury or stroke, axons originating in the brain’s cortex and along the spinal cord become damaged, disrupting motor skills.

Now, according to findings published in the journal Neuron, a team of scientists at Boston Children’s Hospital in the United States has developed a method to promote axon regrowth after injury.

They administered the therapeutic cocktail of molecules to mice with either a spinal cord injury or stroke and observed that the mice were able to recover fine motor skills.

Study senior author Doctor Zhigang He, of Boston Children’s Hospital and Harvard Medical School, said: “In our lab, for the first time we have a treatment that allowed the spinal cord injury and the stroke model to regain functional recovery.”

His team designed the mixture by building on earlier work from Dr. Joshua Sanes’ group at Harvard who focused on optical nerve injuries. Sanes observed that the combination of insulin-like growth factor 1 (IGF1) and a protein called osteopontin (OPN) promoted nerve regrowth and vision improvement in optically-injured mice.

Studying a mouse model of stroke, He’s team made a surprising observation.

He said: “We saw what we expected, axon sprouting in the spinal cord.”

“But we also found something unexpected, increased axon sprouting in the subcortical area.”

By genetic manipulation He’s team ablated the sprouted axons of the CST and found that the improvement diminished. That means the functional recovery was not particularly dependent on sprouting in subcortical regions but on those in the spinal cord.

He added: “The functional outcomes of such subcortical sprouting remain to be tested.”

He said that his team are now in talks with rehab centers to determine the prerequisites of ultimately taking their work forward to clinical trials.

See the full article at this New York Post LINK

Boston Children’s Hospital Vector Article LINK

Medical News Today LINK

Eureka Alert AAAS News Article

Posted in Chronic Spinal Cord Injury Research, Gene Therapy, Regenerative Medicine, Spinal Research | Tagged , , , | 1 Comment