U2FP SCI CureCast now includes the 8th episode!

Join Matthew Rodreick, Kate Willette, and guests for our weekly podcast talking about everything related to finding a cure or therapies for paralysis after spinal cord injury.  Why should we care about the science and the whole process of bringing therapies to the clinic? Because that knowledge is fundamental to gaining a voice in decision-making.

Podcast Episode 8:
Kate and Matthew talk with Lee Thibeault about the process of participating in clinical trials. Lee was one of the first individuals from the SCI community to participate in the early clinical trials of Stem Cell Inc. He talks candidly about his experience, its effects and the importance of participating in clinical trials to further the science to cure paralysis.
LINK

Podcast Episodes 1-7 LINK:

Posted in Advocacy, Rehabilitation, Spinal Research, Unite 2 Fight Paralysis | Leave a comment

Chronic SCI: ReNetX Bio Launched to Advance Innovative Neuro-Regenerative Technology Developed at Yale University

NEW HAVEN, Conn., July 24, 2017 (GLOBE NEWSWIRE) — ReNetX Bio, a company developing first-in-class therapeutics to treat injury to the central nervous system, today announced its launch as a new company with the appointment of Erika Smith as Chief Executive Officer. The company also announced the initiation of a Series A financing round to fund its first clinical trial of its lead therapeutic candidate, Nogo Trap, in patients with chronic spinal cord injury.

ReNetX licensed the rights of the innovative neuro-restorative Nogo Receptor platform technology discovered by Stephen Strittmatter, M.D., Ph.D., at Yale University and founder and scientific advisor to ReNetX. The central nervous system contains major extracellular factors that limit regrowth of neurons. The company has developed a decoy receptor, called Nogo Trap, that binds the growth inhibitors allowing the body to grow nerve fibers naturally and directly targeting restoration across all facets of growth: axonal regeneration (long distance), axonal sprouting (medium distance) and synaptic plasticity.

ReNetX, formerly known as Axerion Therapeutics, currently receives development support for the Nogo Trap chronic SCI program from the National Institutes of Health and the National Center for Advancing Translational Sciences. The company is now actively seeking financing for a Series A financing round to provide the capital needed to initiate and complete a Phase 1/2 clinical trial of Nogo Trap in patients with chronic spinal cord injury.

“Spinal cord injury has been a condition so far resistant to treatment by a variety of therapeutic approaches,” said Dr. Strittmatter. “However, based on the research in my laboratory, we believe that we may have an approach that could benefit these patients. Nogo Trap has demonstrated improved neurologic function following central nervous system damage in several animal models. Based on these promising results, we now believe that Nogo Trap should be evaluated in chronic spinal cord injury patients.”

ReNetX appointed Ms. Smith as part of the recapitalization of the company. She has more than 25 years of experience as an investor and entrepreneur in life sciences. Most recently, she was director of the Blavatnik Fund for Innovation at Yale University.

“Spinal cord injury is one of the most significant unmet medical needs with an annual cost of more than $5 billion per year,” said Ms. Smith. “A treatment that could mitigate even only a part of the condition could both improve quality of life of these patients. When the funding is in place, we anticipate swift patient recruitment for our chronic spinal cord injury clinical trial. In the long-term, conditions beyond spinal cord injury including glaucoma and stroke.”

Article LINK:

Stephen Strittmatter PhD MD Lab Link:

Posted in Chronic Spinal Cord Injury Research, Regenerative Medicine, Spinal Research | Tagged , | 3 Comments

Overexpression of KLF6 in corticospinal tract neurons promotes axon growth after spinal injury

Zimei Wang PhD MD Marquette University

Axonal regeneration in the central nervous system is limited in part by a developmental decline in the intrinsic regenerative capacity of central nervous system (CNS) neurons. Changes in gene expression are likely involved, and thus transcription factors that orchestrate gene expression are attractive targets to understand and overcome intrinsic limits to axon growth in adult neurons. We have shown previously that forced expression of pro-regenerative transcription factors, including Sox11 and a transcriptionally activated form of Krüppel-like factor 7 (VP16-KLF7), can enhance the regenerative ability of injured corticospinal tract (CST) neurons. Here we assessed the ability of KLF6, a transcription factor closely related to KLF7, to promote CST regeneration. KLF6 was delivered to cortical neurons by injection of AAV-KLF6 along with AAV-EGFP tracer, and animals were subjected to pyramidotomy or unilateral cervical hemisection. KLF6 expression promoted a robust increase in midline crossing by transduced (EGFP+) CST axons in the pyramidotomy model, and extensive CST growth in the spinal injury model that extended up to 3mm from the injury site. Immunohistochemistry confirmed viral-mediated upregulation of KLF6 protein, but also revealed endogenous expression of KLF6 in cortical neurons that appeared largely unaffected by spinal axotomy. Intriguingly, forced expression of KLF6 had more modest effects in sensory neurons confronted with spinal injury, causing a decrease in net retraction but not sprouting or regeneration beyond the injury site. To identify potential functional interactions with other pro-regenerative transcription factors, either Sox11 or Myc were co-expressed with KLF6 in cortical neurons challenged with spinal injury. Neither combinatorial treatment resulted in significant increases in CST axon growth above the level of KLF6 alone. Ongoing experiments are testing co-expression of KLF6 with additional pro-regenerative factors including Jun and DCLK. In addition, using CRISPR-mediated knockdown in a Cas9-expressing transgenic mouse, we are currently testing combined KLF6 overexpression and knockdown of PTEN. Finally, RNAseq experiments are underway to identify KLF6 target genes. Overall, these data identify KLF6 as a potent transcriptional promoter of axon regeneration in the injured CST.

Abstract Authors
*Z. WANG, I. VENKATESH, N. KRUEGER, D. NOWAK, B. CALLIF, B. MAUNZE, M. G. BLACKMORE;
Dept. of Biomed. Sci., Marquette Univ., Milwaukee, WI
Disclosures
Z. Wang: None. I. Venkatesh: None. N. Krueger: None. D. Nowak: None. B. Callif: None. B. Maunze: None. M.G. Blackmore: None.

LINK: Session 323 – Spinal Cord Injury Models and Mechanisms

NIH RePorter Link: The Report Expenditures and Results tool allows users to search a repository of NIH-funded research projects and access publications and patents resulting from NIH funding
Project Number: 5R01NS083983-05 Former Number: 5R01NS083983-04
Contact PI / Project Leader: BLACKMORE, MURRAY G
Title: FUNCTIONAL TESTING OF KLF7 IN SPINAL CORD INJURY: AN OPTOGENETIC APPROACH
Awardee Organization: MARQUETTE UNIVERSITY

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

A potent anti-spastic effect after intrathecal NK1 antisense oligonucleotide or subpial AAV9-NK1-ShRNA delivery in rats with chronic spinal transection-induced muscle spasticity

Mariana Bravo Hernandez

BACKGROUND: The spinal NK1 receptor system has been demonstrated to play an important role in the development and maintenance of chronic pain states after peripheral nerve injury. In contrast, its role in the development of spinal hyper-reflexia and muscle spasticity resulting from spinal traumatic injury is not well defined. The goal of the present study was to assess the treatment effect of: i) spinal intrathecal (IT) delivery of NK1 antisense oligonucleotide (NK1-ASO), and ii) subpial (SP) delivery of AAV9-NK1-shRNA in rats with chronic spinal cord transection-induced muscle spasticity. METHODS: Adult Sprague-Dawley (SD) rats (female, 200-300 g) had the Th9 spinal segment transected to induce muscle spasticity. The presence of spasticity was defined as exacerbated EMG response recorded from the gastrocnemius muscle after applying progressively increased paw pressures using von Frey filaments (0.6-26 grams). After baseline spasticity measurement, animals received: i) a single lumbar intrathecal bolus of NK-1-ASO or control antisense oligonucleotide (Cont-ASO), or ii) subpial (SP) AAV9-NK1-shRNA or control AAV9-GFP. Before and after treatment, the presence of spasticity response was measured in 1-week intervals for up to 12 weeks. The effect of each treatment on spinal NK1 expression was evaluated by immunofluorescence and confocal microscopy or by qPCR. RESULTS:In spastic animals receiving IT injection of NK1-ASO, a progressive decrease in measured surface EMG activity after paw tactile stimulation was seen with the maximum effect measured at 2 weeks after injection (p<0.05). A significant anti-spastic affect was still present at 10 weeks after treatment. No changes in spasticity response were measured in animals receiving control ASO. In animals injected SP with AAV9-NK1-shRNA, a comparable anti-spasticity effect was seen at 2 weeks after treatment. Histological and qPCR analysis of the lumbar spinal cord showed a 75-85% reduction in NK1 signal with no change in substance P expression. CONCLUSIONS: These data show that NK1-ASO or AAV9-NK1-shRNA-mediated suppression of spinal NK1 receptor expression may represent a novel therapeutic approach for modulation of chronic spinal injury-induced muscle spasticity and hyper-reflexia.

Abstract Authors
*M. BRAVO HERNANDEZ1, T. YOSHIOZUMI1, M. R. NAVARRO1, K. KAMIZATO1, T. TADOKORO1, O. PLATOSHYN1, S. MARSALA1, J. D. CIACCI2, C. MAZUR3, M. MARSALA1;
1Anesthesiol., 2Neursurgery, Univ. of California San Diego, LA Jolla, CA; 3Ionis Pharmaceuticals, Carlsbad, CA
Disclosures
M. Bravo Hernandez: None. T. Yoshiozumi: None. M.R. Navarro: None. K. Kamizato: None. T. Tadokoro: None. O. Platoshyn: None. S. Marsala: None. J.D. Ciacci: None. C. Mazur: None. M. Marsala: None.

LINK: Session 320 – Injury Responses after Spinal Cord Injury

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

Non-Invasive Paired Stimulation and Anklebot Robot to Improve Lower Extremity Motor Recovery in Chronic Spinal Cord Injury

The Human Spinal Cord Injury Repair laboratory at Burke Medical Research Institute is currently looking for participants with some degree of motor dysfunction in the lower extremity after spinal cord injury for a clinical research study.

The aim of the study is to use robotic kinematics and neurophysiology as possible outcome markers to predict improvement in motor recovery.

Anklebot Clinical Trial for Chronic Incomplete SCI

This project has two objectives:
To investigate the quality of movement in the lower extremity using a robotic device, the Anklebot.
To strength the spared connections between the brain and the muscle after spinal cord injury pairing transcranial magnetic stimulation (TMS) and electrical stimulation. The two stimuli will target the soleus muscle in the lower extremity.

We are expecting to:
Objectively characterized the motor dysfunction using lower limb robotics.
Improve the voluntary motor output using the paired stimulation protocol.

Mar Cortes MD

Mar Cortes, M.D.
Lab Director
Human Spinal Cord Injury Repair Laboratory
Assistant Professor
Weill Cornell Medicine
Role: Principal Investigator

See the Full Article for Addition Enrollment and Eligibility Criteria

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

Spinal cord injury: Using cortical targets to improve motor function

A main goal of rehabilitation strategies in humans with SCI is to strengthen transmission in spared neural networks. Although neuromodulatory strategies have targeted different sites within the central nervous system to restore motor function following SCI, the role of cortical targets remains poorly understood.

“I am excited to see that electrophysiology can be successfully used to guide interventions for recovery of function after spinal cord injury,” says Dr. Perez.

In this study, Drs. Perez, Jinyi Long, Ph.D., and Paolo Federico, Ph.D. used 180 pairs of noninvasive transcranial magnetic stimulation for 30 minutes over the hand representation of the primary motor cortex at an interstimulus interval mimicking the rhythmicity of descending late indirect (I) waves in corticospinal neurons (4.3 ms; late I-wave protocol) or at an interstimulus interval in-between I-waves (3.5 ms; control protocol) on separate days in a randomized order.

Late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following SCI. The researchers found that the excitability of corticospinal projections to intrinsic finger muscles increased in SCI and uninjured participants after the late I-wave but not the control protocol for 30 to 60 minutes after the stimulation. Importantly, individuals with SCI were able to exert more force and electromyographic activity with finger muscles after the stimulation showing an enhanced ability to grasp small objects with their hands.

Full Article at University of Miami Miller School of Medicine

See the FULL Article LINK Science Daily News:

University of Miami Miller School of Medicine
Jinyi Long, Paolo Federico, Monica A. Perez.
A novel cortical target to enhance hand motor output in humans with spinal cord injury. Brain, 2017; 140 (6): 1619 DOI: 10.1093/brain/awx102

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

43 Disability Protesters outside of Senate Mitch McConnell’s office arrested over proposed severe Medicaid cuts.

LINK: The Senate Puts Medicaid on the Chopping Block

A draft version of the AHCA released Thursday shows even deeper cuts to the program than the House version.

Senate Health Care Protest

Many disabled people in wheelchairs were arrested outside of Senate Majority Leaders Office.

The new AHCA is a lot like the old AHCA.

After weeks of secret gestation in back rooms, the Senate released a discussion draft of the chamber’s version of the American Health Care Act. Like the version passed through the House to cheers in May, it is likely to make health care less affordable for low-income, sick, and near-elderly people; it makes Obamacare tax credits for exchange coverage less generous; it restricts and slashes Medicaid funding deeply over the next decade; and it attempts to smooth euphemistically-named “market disruptions” from all those reforms by injecting billions into state funds and reinsurance.

There are some substantial changes in the specifics, though. For starters, the Senate bill would tweak the House bill’s tax subsidy for private insurance purchased on the exchanges. The final version of the House bill provided a tax credit to people making up to 400 percent of the federal poverty line that would be less generous than the existing ACA credits. It would also reduce the amount of expenses covered as recipients get older and have more expenses.

The Senate’s version would cut the eligibility for premium tax credits to those earning up to 350 percent of the poverty line. It would be slightly more generous for poor and near-poor people, although credit percentages would taper off more sharply as recipients grow older, and they would be severely restricted for people as their income approaches that 350 percent threshold. Unlike the House plan, however, the Senate plan would fund Obamacare exchange cost-sharing subsidies through 2019, which would soften some of the immediate impacts of a less generous tax credit.

See the Full Article at The Atlantic by VANN R. NEWKIRK II

Disability Advocacy Protesters were dragged out of the hallway in front of McConnell’s office after the Senate unveiled its health care bill.

CNN Article

Posted in Advocacy

Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin–N-cadherin pathway after SCI

Masamitsu Hara Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis. We also found that type I collagen was highly expressed in the spinal cord during the scar-forming phase and induced astrocytic scar formation via the integrin–N-cadherin pathway. In a mouse model of spinal cord injury, pharmacological blockade of reactive astrocyte–type I collagen interaction prevented astrocytic scar formation, thereby leading to improved axonal regrowth and better functional outcomes. Our findings reveal environmental cues regulating astrocytic fate decisions, thereby providing a potential therapeutic target for CNS injury.

Masamitsu Hara1,2, Kazu Kobayakawa2 , Yasuyuki Ohkawa3 , Hiromi Kumamaru2, Kazuya Yokota2, Takeyuki Saito1,2, Ken Kijima1,2, Shingo Yoshizaki1,2, Katsumi Harimaya2, Yasuharu Nakashima2 & Seiji Okada1,2

Nature Medicine (2017) doi:10.1038/nm.4354
Received 29 September 2016 Accepted 14 April 2017 Published online 19 June 2017

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Spinal Research, Stem Cell Research | Tagged ,

SCI Stem-cell pioneer enters the political field in California

Democrat Hans Keirstead is one of five Democrats challenging Rep. Dana Rohrabacher, R-Costa Mesa.

Hans Keirstead, a pioneering stem-cell biologist and multimillionaire businessman who was a professor at UC Irvine for 14 years, announced Thursday he would join the field of Democrats challenging Rep. Dana Rohrabacher, R-Costa Mesa.

Keirstead said the leading motivation for his decision to run was the country’s health care system, with specific concerns about Republican plans that could reduce those with insurance by 23 million those with insurance and with regulatory fee hikes for companies doing lifesaving research.

“That is going to have a direct effect on development in the biomedical field,” the Laguna Beach resident said. “There’s an ignorance in Washington about health care … an ignorance of the system.”

Keirstead, 50, is a Canadian immigrant who sold his Irvine-based California Stem Cell Inc. for more than $100 million in 2014. His biography at Aivita Biomedical, where he’s currently CEO, says that he raised $93 million in grants and donations while at UC Irvine and $22 million in grants at his current job.

Orange County Register: Martin Wisckol LINK

Posted in Advocacy | Tagged

Patients with Complete Paralysis Show Additional Recovery of Arm, Hand and Finger Function at 9-months After Treatment with Asterias’ AST-OPC1

Third patient recovers two motor levels; three of six (50%) patients in AIS-A 10 million cell cohort have now recovered two motor levels on at least one side

Asterias OPC.


FREMONT, Calif., June 13, 2017 /PRNewswire/ –Asterias Biotherapeutics, Inc. (NYSE MKT: AST), a biotechnology company pioneering the field of regenerative medicine, today announced that new 9-month follow-up data from the AIS-A 10 million cell cohort in the company’s ongoing SCiStar Phase 1/2a clinical trial shows three of six (50%) patients have now recovered two levels of motor function and previously-announced improvements in arm, hand and finger function at 3-months and 6-months following administration of AST-OPC1 have been confirmed and further increased at 9-months.

“The new efficacy results show that previously reported meaningful improvements in arm, hand and finger function in the 10 million cell cohort treated with AST-OPC1 cells have been maintained and in some patients have been further enhanced even 9 months following dosing,” stated Dr. Edward Wirth III, Chief Medical Officer. “Gains in motor function, such as the improvements observed in the SCiStar study to date, have been shown to increase a patient’s ability to function independently following complete cervical spinal cord injuries. We are increasingly encouraged by these continued positive results, which are remarkable compared with spontaneous recovery rates observed in a closely matched untreated patient population.”

Jane S. Lebkowski, Ph.D., Asterias’ President of R&D and Chief Scientific Officer, will present the 9-month efficacy and safety data on the AIS-A 10 million cell cohort later today during the International Society for Stem Cell Research (ISSCR) 2017 Annual Meeting held in Boston, MA. The full slide presentation will be available at http://asteriasbiotherapeutics.com/inv_events_presentations.php.

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