Discovery Offers New Hope to Repair Spinal Cord Injuries

By Dana G. Smith, PhD / Gladstone News / April 24, 2017

Todd McDevitt (right), Jessica Butts (center) and Dylan McCreedy (left) created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. [Photo: Chris Goodfellow, Gladstone Institutes]


Scientists at the Gladstone Institutes created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. These cells, called V2a interneurons, transmit signals in the spinal cord to help control movement. When the researchers transplanted the cells into mouse spinal cords, the interneurons sprouted and integrated with existing cells.

V2a interneurons relay signals from the brain to the spinal cord, where they ultimately connect with motor neurons that project out to the arms and legs. The interneurons cover long distances, projecting up and down the spinal cord to initiate and coordinate muscle movement, as well as breathing. Damage to V2a interneurons can sever connections between the brain and the limbs, which contributes to paralysis following spinal cord injuries.

“Interneurons can reroute after spinal cord injuries, which makes them a promising therapeutic target,” said senior author Todd McDevitt, PhD, a senior investigator at Gladstone and a professor in the Department of Bioengineering and Therapeutic Sciences at UCSF. “Our goal is to rewire the impaired circuitry by replacing damaged interneurons to create new pathways for signal transmission around the site of the injury.”

Several clinical trials are testing cell replacement therapies to treat spinal cord injuries. Most of these trials involve stem cell–derived neural progenitor cells, which can turn into several different types of brain or spinal cord cells, or oligodendrocyte progenitor cells, which create the myelin sheaths that insulate and protect nerve cells. However, these approaches either do not attempt or cannot reliably produce the specific types of adult spinal cord neurons, such as V2a interneurons, that project long distances and rebuild the spinal cord.

Read the FULL News Article at the Gladstone Institute LINK

PNAS Abstract LINK

ABSTRACT VIDEO

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

Robotic platform maximizing gravity-dependent gait interactions to train standing and walking after neurological disorders

Jean Baptiste Mignardot (G. Courtine Lab)

Gait recovery after neurological disorders requires re-mastering the interplay between body mechanics and gravitational forces. Despite the importance of gravity-dependent gait interactions for promoting this learning, this essential aspect of gait rehabilitation have received little attention. Here, we introduce a robotic interface that assists trunk movements in order to maximize gravity-dependent gait interactions during highly participative locomotion within a large and safe environment. We elaborated an algorithm that automatically configures multidirectional forces applied to the trunk based on patient-specific needs. This robotic assistance enabled walking in non-ambulatory individuals with spinal cord injury and stroke, and allowed less impaired individuals to execute skilled locomotion that they could not perform without robotic assistance. The robotic interface improved locomotor performance after a single gait training session, whereas the same amount of training restricted to vertical support on a treadmill did not ameliorate gait. These results establish a new rehabilitation framework to augment motor recovery after neurological disorders.

Abstract Authors: *J.B. MIGNARDOT1,2, C. G. LE GOFF1,2, R. VAN DEN BRAND1,2, N. FUMEAUX1, S. CARDA4,2, J. VON ZITZEWITZ1, J. BLOCH2,3, G. COURTINE1,2; 1EPFL, Lausanne, Switzerland; 2Clin. Neurosciences, 3Neurosurg., Univ. Hosp. of Vaud, Lausanne, Switzerland; 4Neurorehabilitation, Univ. Hosp. of Vaud, Lausanne, Switzerland

Disclosures: J. Mignardot: None. C.G. Le Goff: None. R. van den Brand: None. N. Fumeaux: None. S. Carda: None. J. von Zitzewitz: None. J. Bloch: None. G. Courtine: None.

LINK: Session 158 – Spinal Cord Injury and Plasticity

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Mayo pushes forward with Neuromodulation Discoveries for SCI

Peter J. Grahn, PhD


Drs. Peter Grahn, Kendall Lee, Igor Lavrov, and Kristin Zhao, from Mayo Clinic in Rochester, MN, review the results of their study appearing in the April 2017 issue of Mayo Clinic Proceedings showing volitional movement, standing, and step-like actions via spinal cord neuromodulation in a patient with chronic paralysis due to spinal cord injury.

Read the Full Publication Text Here: Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia

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Gait rehabilitation enabled by epidural electrical stimulation of lumbar segments in a person with a chronic incomplete SCI

Various studies in animal models showed that robot-assisted gait rehabilitation enabled by epidural electrical stimulation of the lumbar spinal cord improves the recovery of leg motor control after spinal cord injury. Recent studies showed that this stimulation is also capable of activating lumbar spinal circuits in paraplegic people. Here, we conducted a preliminary study to evaluate the therapeutic impact of a gait rehabilitation program enabled by an overground robotic bodyweight support and continuous epidural electrical stimulation in a non-ambulatory person with a chronic incomplete spinal cord injury. The participant suffered a herniated disc collapse at the cervical level, which led to severe deficits on the left leg and moderate impairments on the right leg (AIS-C). After following a conventional rehabilitation program for more than one year after injury, she was not able to walk overground, even with assistive devices. She had previously been implanted with an epidural electrode array over lumbar spinal cord segments to alleviate neuropathic pain in the legs. We searched the electrode configurations in this array that targeted the muscles that the participant could not access voluntarily. Continuous stimulation through these electrode configurations improved a number of relevant gait parameters during locomotion. The participant then underwent a gait rehabilitation program that was conducted overground using a multidirectional robotic support system, and facilitated with the personalized stimulation protocols. After completion of the gait rehabilitation program, the participant was able to use a walker to progress overground without robotic assistance and without stimulation. Her WISCI-II score had thus increased from zero to thirteen, while her AIS score converted from C to D. Urodynamic examination revealed the disappearance of uninhibited bladder contractions and detrusor sphincter dyssynergia. This study provides preliminary evidence that robot-assisted gait rehabilitation enabled by epidural electrical stimulation may promote clinically relevant neurological improvements that persist without stimulation.

Abstract Authors
*C. G. LE GOFF1,3, J.-B. MIGNARDOT1,3, R. VAN DEN BRAND1,3, M. CAPOGROSSO2, I. FODOR4, G. EBERLE4, B. SCHURCH5, S. CARDA3,4, J. VON ZITZEWITZ1, J. BLOCH3,6, G. COURTINE1,3;
1Brain Mind Institute, Ctr. for Neuroprosthetics, 2Ctr. for Neuroprosthetics, Inst. of Bioengineering, Ecole Polytechnique Federale De Lausanne, Lausanne, Switzerland; 3Clin. Neurosci., 4Neurorehabilitation, 5Neuro-urology, 6Neurosurg., Univ. Hosp. of Vaud (CHUV), Lausanne, Switzerland
Disclosures
C.G. Le Goff: None. J. Mignardot: None. R. van den Brand: None. M. Capogrosso: None. I. Fodor: None. G. Eberle: None. B. Schurch: None. S. Carda: None. J. von Zitzewitz: None. J. Bloch: None. G. Courtine: None.

LINK: Session 158 – Spinal Cord Injury and Plasticity

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

Stretching the boundaries of neural implants

Rubbery, multifunctional fibers could be used to study spinal cord neurons and potentially restore function.
David L. Chandler | MIT News Office

Image: Chi (Alice) Lu and Seongjun Park Credit: MIT

Implantable fibers have been an enormous boon to brain research, allowing scientists to stimulate specific targets in the brain and monitor electrical responses. But similar studies in the nerves of the spinal cord, which might ultimately lead to treatments to alleviate spinal cord injuries, have been more difficult to carry out. That’s because the spine flexes and stretches as the body moves, and the relatively stiff, brittle fibers used today could damage the delicate spinal cord tissue.

Now, researchers have developed a rubber-like fiber that can flex and stretch while simultaneously delivering both optical impulses, for optoelectronic stimulation, and electrical connections, for stimulation and monitoring. The new fibers are described in a paper in the journal Science Advances, by MIT graduate students Chi (Alice) Lu and Seongjun Park, Professor Polina Anikeeva, and eight others at MIT, the University of Washington, and Oxford University.

Read the Full Article Here:

Read the Full Paper at Science Advances HERE:

Engineering a spinal cord repair kit at MIT – Science Nation (Professor Polina Anikeeva) Posted Earlier

Posted in Biomaterials, Chronic Spinal Cord Injury Research, Regenerative Medicine, Spinal Research | Leave a comment

Rerouting cortical drive through residual spinal tissue mediates motor function recovery after severe SCI

A severe contusion of thoracic segments disrupts the motor-circuit communication matrix linking the brain and the spinal cord. Electrochemical stimulation applied over lumbar segments restored this communication, which enabled volitional control of leg movements in rodents and humans with motor complete paralysis. However, the circuit-level mechanisms through which the cortical drive regains functional access to the spinal circuits controlling leg movements during electrochemical stimulation remain poorly understood. Using mice expressing light-sensitive channels in cortical projection neurons, we first showed that electrochemical stimulation enabled the hindlimb motor cortex to regain a graded control over hindlimb locomotor movements in otherwise paralyzed animals. Using virus-mediated tract tracing and circuit-specific inactivation techniques, we found that after injury the cortical drive is rerouted through glutamatergic reticular neurons with residual projections below the injury. Robot-assisted gait training enabled by electrochemical stimulation promoted an extensive reorganization of these pathways. We found a robust growth of motor cortex projections into the reticular formation, and a substantial sprouting of residual reticulospinal axons into specific regions of the spinal cord below the injury. We established causal relationships between this anatomical reorganization and the recovery of voluntary leg motor control in response to gait rehabilitation. These results illustrate the remarkable capability of neural pathways to reorganize in order to mediate motor recovery, even after the most severe types of spinal cord injury.

Abstract Authors
*L. ASBOTH, Q. BARRAUD, L. FRIEDLI, J. BEAUPARLANT, C. MARTINEZ-GONZALEZ, S. ANIL, G. PIDPRUZHNYKOVA, E. REY, L. BAUD, J. KREIDER, M. ANDERSON, J. VON ZITZEWITZ, G. COURTINE;
Swiss Federal Inst. of Technol., Lausanne, Switzerland
Disclosures
L. Asboth: None. Q. Barraud: None. L. Friedli: None. J. Beauparlant: None. C. Martinez-Gonzalez: None. S. Anil: None. G. Pidpruzhnykova: None. E. Rey: None. L. Baud: None. J. Kreider: None. M. Anderson: None. J. von Zitzewitz: None. G. Courtine: None.

LINK: Session 158 – Spinal Cord Injury and Plasticity

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Rehabilitation, Spinal Research | 1 Comment

Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury

Kathren L. Fink, Francesc López-Giráldez, In-Jung Kim, Stephen M. Strittmatter, William B.J. Cafferty Open Access
DOI: http://dx.doi.org/10.1016/j.celrep.2017.02.058

Highlights
•Mechanisms driving functional plasticity of intact CNS circuits are unknown
•Retrograde spinal tracing reveals CST neurons undergoing functional plasticity
•Transcriptional profiling of these neurons reveals pro-axon growth targets
•Molecular modulation of the identified LPA-LPPR1 axis enhances plasticity post-SCI

Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact circuitry. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from Ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild-type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation.

See the Full Article at Cell.com

Posted in Chronic Spinal Cord Injury Research, Spinal Research

U.S. Capitol Police arrest people in wheelchairs inside the Capitol Rotunda over Trumpcare Health Bill

A U.S. Capitol Police spokeswoman says 54 people, many in wheelchairs, were arrested Wednesday in the Capitol Rotunda as they protested the health care bill being considered in the House.

Spokeswoman Eva Malecki says the 41 women and 13 men arrested were charged under District of Columbia law that makes it illegal for someone to obstruct passage through a public building and continue to do so after being instructed by police to cease. Eva Malecki, says arrests were made and additional details will be provided later.

Chanting “Rather go to jail than die without Medicaid,” the protesters were led out individually or in pairs by members of the U.S. Capitol Police.

One of the protesters being led out says she is part of ADAPT, an organization that promotes rights for people with disabilities.

One protester is displaying a sign that says “Medicaid = Life 4 Disabled.”

The GOP-led bill would limit future federal financing for Medicaid.

VIDEO LINK:

ABC NEWS WIRE LINK:

Posted in Advocacy | 1 Comment

What Budget Cuts Might Mean for US Science

A look at the historical effects of downsized research funding suggests that the Trump administration’s proposed budget could hit early-career scientists the hardest.

By Diana Kwon | March 21, 2017

The Trump administration’s proposed federal budget has already evoked significant backlash from scientists and science advocacy organizations across the United States. The FY2018 budget proposal, released by the White House last week, includes massive cuts to agencies that fund research, including the National Institutes of Health (NIH) and the Environmental Protection Agency (EPA).

Despite the alarm surrounding the news of proposed science funding cuts, experts stressed that the budget request is unlikely to pass as is. “This is the president’s proposal . . . this is a statement from the White House about what they would like to see,” Rush Holt, CEO of the American Association for the Advancement of Science (AAAS), told The Scientist. “It’s Congress that makes the appropriations.”

Congress has traditionally shown bipartisan support for biomedical research, said Elias Zerhouni, who was director of the NIH from 2002 until 2008. “I used to say that ‘Disease knows no party affiliation’ and ‘Disease knows no politics,’ and frankly, that’s my experience, so I’m hopeful that the damage will not be as great as what is being proposed.”

Read the full article in The Scientist: HERE

Posted in Chronic Spinal Cord Injury Research, Regenerative Medicine, Rehabilitation, Spinal Research

CITC LTD and partners on personalized stem cell therapies for injury and diseases of the CNS

CITC Ltd has recently concluded a non-esclusive license agreement with Provendis GmbH, a technology transfer agency of 27 universities of North Rhine-Westphalia, including the University of Bonn, for a manufacturing technology of autologous induced neural stem cells (iNSC) from adult cells that are harvested from simple skin biopsy or from other somatic sources.

Directly reprogrammed autologous iNSCs are seen as a powerful and safe tool to treat patients with neurological illnesses and injuries, that may occur while they age.

In line with CITC ltd’s governing mission, this license agreement helps develop further our unique portfolio of technologies and Intellectual Property in the field of molecular diagnostics, nano-medicine, and advanced therapies, and to establish a translational path toward clinical use in humans, subject to successful clinical trials.

See the Full Article HERE

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