Worldwide licensing agreement made on peptide developed in Silver laboratory at Case Western Reserve University

VANCOUVER, British Columbia, July 18, 2018 (GLOBE NEWSWIRE) — NervGen Pharma Corp. (“NervGen”), in Vancouver, and Case Western Reserve University (“Case Western Reserve”) in Cleveland have entered into an exclusive worldwide licensing agreement to research, develop and commercialize a patented technology with potential to bring new therapies for spinal cord injury and other conditions associated with nerve damage.

The technology was developed in the laboratory of Dr. Jerry Silver, a leading spinal cord injury and regenerative medicine researcher at Case Western Reserve. Dr. Silver’s research has implicated protein tyrosine phosphatase sigma (PTPs) as a key neural receptor which inhibits nerve regeneration through regions of scarring in spinal cord injury and other medical conditions.

Targeted treatment against PTPs with an agent known as ISP promoted regeneration of damaged nerves and functional improvement in animal models for various medical conditions. A series of receptor antagonists that can be delivered systemically have been identified including an analogue of ISP that is ready for clinical development.

Read the Full Article at Globe Newswire.  

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Nick Terrafranca from NeuroRecovery Technologies

NeuroRecovery Technologies specializes in Spinal Cord Stimulation for spinal cord injury. Nick Terrafranca, CEO, describes the technology and an update on the progress of their research.

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In a Break with Dogma, Myelin Boosts Neuron Growth in Spinal Cord Injuries

The molecule inhibits adult axon regeneration, but appears to stimulate young neurons by Scott LaFee

Recovery after severe spinal cord injury is notoriously fraught, with permanent paralysis often the result. In recent years, researchers have increasingly turned to stem cell-based therapies as a potential method for repairing and replacing damaged nerve cells. They have struggled, however, to overcome numerous innate barriers, including myelin, a mixture of insulating proteins and lipids that helps speed impulses through adult nerve fibers but also inhibits neuronal growth.

But in a new paper, published in the May 23 online issue of Science Translational Medicine, researchers at University of California San Diego School of Medicine report that adult rat myelin actually stimulated axonal outgrowth in rat neural precursor cells (NPCs) and human induced pluripotent (iPSC)-derived neural stem cells (NSCs).

Dr. Mark Tuszynski Professor of neuroscience and director of the UC San Diego Translational Neuroscience Institute

“It’s really a remarkable finding because myelin is known to be a potent inhibitor of adult axon regeneration,” said Mark Tuszynski, MD, PhD, professor of neuroscience and director of the UC San Diego Translational Neuroscience Institute. “But that isn’t the case with precursor neurons or those derived from stem cells.”

Neuroscience News Article

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

A new microtubule-based approach for augmenting nerve regeneration

Andrew Matamoros, Drexel Baas Lab

Most studies on microtubules in the nervous system have focused on the dynamic properties of the microtubules, with stabilization by taxol and related drugs being proposed as a therapeutic for nerve injury. However, while initial indications were hopeful, more recent observations have called into question whether such drugs directly help nerves to regenerate or if they only provide a small advantage by reducing proliferation within the glial scar. In particular, there is concern that microtubule-stabilizing drugs will impede the ability of the regenerating axon to navigate to its target, given that microtubule dynamics are known to be important for growth cone guidance. Even so, microtubules remain a worthy target, given that they are downstream of many of the growth factors and cell signaling pathways that have already been shown to be relevant to nerve regeneration. We hypothesize that a better approach than microtubule stabilization may be to boost the levels of the more dynamic component of the microtubule mass, which is more akin to how axons grow and navigate during development. Previously we showed in work on fetal neurons that fidgetin is a microtubule-severing protein that pares down the dynamic portions of microtubules in the axon, such that depleting fidgetin results in an increase in dynamic microtubule mass and improved axon growth. Using AAV5 to transduce adult dorsal root ganglion neurons with fidgetin shRNA, we have now tested whether fidgetin knockdown assists axon regeneration in a novel in vitro system in which the cells are plated on a laminin substrate with spots of aggrecan, which is a growth-inhibitory component of glial scarring after spinal cord injury. When dried onto glass coverslips, the spots create a gradient of aggrecan and lamanin that increases from the inside-out. Fidgetin knockdown resulted in faster-growing axons off the spots, as well as more crossing of axons through the laminin-aggrecan border, in both directions. With fidgetin depleted, axons of neurons on the spots grew against the concentration gradient of aggrecan, unlike their control counterparts. In addition, the fidgetin-depleted axons had less dystrophic growth cones than controls, with microtubules that invaded into the peripheral regions of broader growth cones than controls. These in vitro results bode well for improved regeneration in an in vivo model for nerve regeneration that we are currently pursuing.

Authors*A. J. MATAMOROS1, D. WU2, V. J. TOM2, L. BAKER3, D. SHARP3, P. W. BAAS2;
1Mol. and Cell. Biol. and Genetics/Neurobiology, Drexel Col. of Med., Philadelphia, PA; 2Neurobio. and Anat., Drexel Univ. Col. of Med., Philadelphia, PA; 3Albert Einstein Col. of Med., Bronx, NYDisclosures A.J. Matamoros: None. D. Wu: None. V.J. Tom: None. L. Baker: None. D. Sharp: None. P.W. Baas:None.

Grant Support

NIH 2R01NS028785-25

Craig H. Neilsen ID#259350

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

Lumbosacral spinal cord epidural stimulation improves voiding function after human SCI

Authors: Herrity AN1,2, Williams CS3, Angeli CA1,4, Harkema SJ1,2,4, Hubscher CH5,6

Deficits in urologic function after spinal cord injury (SCI) manifest both as a failure to store and empty, greatly impacting daily life. While current management strategies are necessary for urological maintenance, they oftentimes are associated with life-long side effects. Our objective was to investigate the efficacy of spinal cord epidural stimulation (scES) as a promising therapy to improve bladder control after SCI. A bladder mapping study was undertaken for sixteen sessions over the course of four months in an individual with chronic, motor complete SCI. Varying combinations of stimulating cathode electrodes were initially tested during filling cystometry resulting in the identification of an effective configuration for reflexive bladder emptying at the caudal end of the electrode array. Subsequent systematic testing of different frequencies at a fixed stimulus intensity and pulse width yielded lowest post-void residual volumes at 30 Hz. These stimulation parameters were then tested in four additional research participants and found to also improve reflexive voiding efficiency. Taken together with SCI studies on step, stand, voluntary motor control and cardiovascular regulation, these findings further corroborate that scES has an all-encompassing potential to increase the central state of excitability, allowing for the control of multiple body functions, including the urological system.

Read the Full Open Access Publication at Nature

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Gene therapy reverses rat’s paralysis at King’s College London

Researchers at King’s have shown that rats with spinal cord injuries can re-learn skilled hand movements after being treated with a gene therapy that could be switched on and off using a common antibiotic.

Researchers at King’s College London and the Netherlands Institute for Neuroscience have shown that rats with spinal cord injuries can re-learn skilled hand movements after being treated with a gene therapy.

People with spinal cord injury often lose the ability to perform everyday actions that require coordinated hand movements, such as writing, holding a toothbrush or picking up a drink. Regaining hand function is the top priority for patients and would dramatically improve independence and quality of life.

The researchers had to overcome a problem with the immune system recognising and removing the gene switch mechanism. To get around this, the researchers worked with colleagues in the Netherlands to add a ‘stealth gene’ which hides the gene switch from the immune system.

Professor Joost Verhaagen at the Netherlands Institute for Neuroscience says: ‘The use of a stealth gene switch provides an important safeguard and is an encouraging step toward an effective gene therapy for spinal cord injury. This is the first time a gene therapy with a stealth on/off switch has been shown to work in animals.’

    The gene therapy is not yet ready for human trials. While the ability to switch a therapeutic gene off provides a safeguard, the researchers found a small amount of the gene remained active even when switched off. They are now working on shutting the gene down completely and moving towards trials in larger species.

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

Jan-Eric Ahlfors CEO and CSO of Fortuna Fix Presented at Unite to Cure

Jan-Eric Ahlfors, CEO and CSO of Fortuna, presented at the Fourth International Vatican Conference “Unite to Cure”. Fortuna’s directly reprogrammed cell technology platform was in a session entitled “The Pharmacy of the Future – Stem Cells and Cardiovascular, Pulmonary and Neurodegenerative Diseases”.

Fortuna is a private regenerative medicine 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 has its lead programs in Spinal Cord Injury and Parkinson’s disease and on-going development efforts in Stroke, Traumatic Brain Injury, Hearing Loss and ALS. The company has developed a proprietary, large-scale and fully automated manufacturing system for production of autologous drNPCs. As a company, we have prioritized fully automated manufacturing for production of our personalized directly reprogrammed neural precursor cells (“drNPCs”) as we recognize manufacturing as a significant hurdle most companies face in large-scale manufacturing of cellular therapies.

With its fully automated manufacturing system, Fortuna aims to be the first to manufacture and bring to the clinic personalized neural precursor cells for treatment of diseases in the fields of neurodegeneration and neurotrauma. Manufacturing of autologous drNPCs is accomplished with a rapid, high throughput, and fully automated process, which does not involve engineering, animal components, or staged pluripotency. Patients suffering from neurotrauma or neurodegeneration will be able to get treatment with their own neural cells providing functional integration without immunosuppression or ethical issues (the technology uses no fetal, embryonic-like, or other ethically challenging processes).

“Fortuna’s mission is to “Cure CNS diseases with next-generation ethical regenerative medicine solutions” and we are honored to be part of this extraordinary event with a goal synergistic to our efforts”, said Jan-Eric Ahlfors, CEO and CSO of Fortuna. For more information, please visit http://fortunafix.com.

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

Marquette professor awarded $1.6 million NIH grant for spinal cord injury research

Marquette University professor Murray Blackmore was awarded a $1.6 million grant from the National Institutes of Health to continue his research of spinal cord injury and paralysis.

Dr. Murray Blackmore, associate professor of biomedical sciences in the College of Health Sciences at Marquette University. courtesy Biz News

Dr. Murray Blackmore, associate professor of biomedical sciences in the College of Health Sciences at Marquette University.

It’s the second $1.6 million NIH grant that Blackmore, an associate professor of biomedical sciences in the College of Health Sciences, has received in five years.

Blackmore’s primary research focuses on the use of gene therapy to treat brain cells damaged in spinal cord injuries, leading to nerve growth and regeneration at the injury site. The therapy can reverse paralysis, leading to partial regained movement and motor control.

With the findings funded from Blackmore’s first NIH grant, his lab will continue to the next phase of the project, which includes the use of stem cells and a recently developed nerve labeling technique to better visualize nerve growth and regeneration.

“To restore motor control after trauma in the brain and spinal cord, cut nerve fibers must regrow, and critically, must reconnect with the appropriate target cells, forming a ‘bridge’ across the injury,” Blackmore said. “My team and I are testing additional activity-based therapies to amplify and enhance the connections of the regrown nerves in order to make that nerve ‘bridge’ more structurally sound, with the goal of increasing motor control and function.”

See the Full Story at Biz News Milwaukee Business News

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Modulation of Receptor Protein Tyrosine Phosphatase Sigma Increases Chondroitin Sulfate Proteoglycan Degradation through Cathepsin B Secretion to Enhance Axon Outgrowth

Authors: Amanda Phuong Tran, Sapna Sundar, Meigen Yu, Bradley T. Lang and Jerry Silver

Amanda Tran, Case Western Reserve University


Abstract: Severed axon tips reform growth cones following spinal cord injury that fail to regenerate, in part, because they become embedded within an inhibitory extracellular matrix. Chondroitin sulfate proteoglycans (CSPGs) are the major axon inhibitory matrix component that is increased within the lesion scar and in perineuronal nets around deafferented neurons. We have recently developed a novel peptide modulator (intracellular sigma peptide) of the cognate receptor of CSPGs, protein tyrosine phosphatase σ (RPTPσ), which has been shown to markedly improve sensorimotor function, micturition, and coordinated locomotor behavior in spinal cord contused rats. However, the mechanism(s) underlying how modulation of RPTPσ mediates axon outgrowth through inhibitory CSPGs remain unclear. Here, we describe how intracellular sigma peptide (ISP) modulation of RPTPσ induces enhanced protease Cathepsin B activity. Using DRG neurons from female Sprague Dawley rats cultured on an aggrecan/laminin spot assay and a combination of biochemical techniques, we provide evidence suggesting that modulation of RPTPσ regulates secretion of proteases that, in turn, relieves CSPG inhibition through its digestion to allow axon migration though proteoglycan barriers. Understanding the mechanisms underlying RPTPσ modulation elucidates how axon regeneration is impaired by proteoglycans but can then be facilitated following injury.

SIGNIFICANCE STATEMENT Following spinal cord injury, chondroitin sulfate proteoglycans (CSPGs) upregulate and potently inhibit axon regeneration and functional recovery. Protein tyrosine phosphatase σ (RPTPσ) has been identified as a critical cognate receptor of CSPGs. We have previously characterized a synthetic peptide (intracellular sigma peptide) that targets the regulatory intracellular domain of the receptor to allow axons to regenerate despite the presence of CSPGs. Here, we have found that one important mechanism by which peptide modulation of the receptor enhances axon outgrowth is through secretion of a protease, Cathepsin B, which enables digestion of CSPGs. This work links protease secretion to the CSPG receptor RPTPσ for the first time with implications for understanding the molecular mechanisms underlying neural regeneration and plasticity.

LINK

This work was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke NS025713, the Kaneko Family Fund, the Brumagin-Nelson Fund, and the Hong Kong Spinal Cord Injury Fund.

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Translating promising strategies for bowel and bladder management in spinal cord injury

Loss of control over voiding following spinal cord injury (SCI) impacts autonomy, participation and dignity, and can cause life-threatening complications. The importance of SCI bowel and bladder dysfunction warrants significantly more attention from researchers in the field. To address this gap, key SCI clinicians, researchers, government and private funding organizations met to share knowledge and examine emerging approaches. This report reviews recommendations from this effort to identify and prioritize near-term treatment, investigational and translational approaches to addressing the pressing needs of people with SCI.

Authors: Tracey L.Wheeler Bowel and Bladder Workshop Participants William deGroat Kymberly Eisner Anton Emmanuel Jennifer French Warren Grille Michael J.Kennelly Andrei Krassioukov Bruno Gallo Santa cruz Fin Biering-Sørenseni Naomi Kleitman

Read the Full Publication Here:

Posted in Chronic Spinal Cord Injury Research, Spinal Research