Stem Cell Injections Improve Spinal Injuries in Rats

Source: University of California - San Diego
Date: May 28, 2013

Summary:

An international team led by researchers at the University of California, San Diego School of Medicine reports that a single injection of human neural stem cells produced neuronal regeneration and improvement of function and mobility in rats impaired by an acute spinal cord injury (SCI).  The findings are published in the May 28, 2013 online issue of Stem Cell Research & Therapy.

The rats received the pure stem cell grafts three days after injury (no other supporting materials were used) and were given drugs to suppress an immune response to the foreign stem cells. Marsala said grafting at any time after the injury appears likely to work in terms of blocking the formation of spinal injury cavities, but that more work would be required to determine how timing affects functional neurological benefit. The human stem cells, said the scientists, appeared to vigorously take root at the injury site.  Scientists observed the grafted stem cells appeared to be doing two things: stimulating host neuron regeneration and partially replacing the function of lost neurons.

The scientists used a line of human embryonic stem cells recently approved for Phase 1 human trials in patients with chronic traumatic spinal injuries. Marsala said the ultimate goal is to develop neural precursor cells (capable of becoming any of the three main cell types in the nervous system) from induced pluripotent stem cells derived from patients, which would likely eliminate the need for immunosuppression treatment.

Pending approval by UC San Diego’s Institutional Review Board, the next step is a small phase 1 trial to test safety and efficacy with patients who have suffered a thoracic spinal cord injury (between vertebrae T2-T12) one to two years earlier, and who have no motor or sensory function at or below the spinal injury site.

StemCells, Inc. Announces First Patient Cohort Completes Spinal Cord Injury Trial - Gains in Sensory Function Persist 12 Months After Stem Cell Transplant

Source: StemCells, Inc.
Date: February 12, 2013

Summary:

NEWARK, Calif. -- StemCells, Inc. today announced that the twelve-month data from the first patient cohort in the Company's Phase I/II clinical trial of its proprietary HuCNS-SC® product candidate (purified human neural stem cells) for chronic spinal cord injury continued to demonstrate a favorable safety profile, and showed that the considerable gains in sensory function observed in two of the three patients at the six-month assessment have persisted. The third patient remains stable. A summary of the data was presented today by Martin McGlynn, President and CEO, at the 15th Annual BIO CEO & Investor Conference. By completing the twelve-month assessment, the first patient cohort has now completed the trial, and has entered into a separate follow-up study for long-term observation.

Neuralstem Receives FDA Approval To Commence Spinal Cord Injury Trial

Source: Neuralstem, Inc.
Date: January 14, 2013

Summary:

ROCKVILLE, Md. -- Neuralstem, Inc. announced that it received approval from the United States Food and Drug Administration (FDA) to commence a Phase I safety trial of its lead cell therapy candidate, NSI-566, in chronic spinal cord injury patients. This open-label, multi-site study, will enroll up to eight patients with thoracic spinal cord injuries (T2-T12), who have an American Spinal Injury Association (AIS) A level of impairment, between one and two years after injury. AIS A impairment refers to a patient with no motor or sensory function in the relevant segments at and below the injury, and is considered to be complete paralysis.

The primary objective of the study is to determine the safety and toxicity of human spinal stem cell transplantation for the treatment of paralysis and related symptoms due to chronic spinal cord injury (SCI). The secondary objectives of the study are to evaluate graft survival in the transplant site by MRI, as well as the effectiveness of transient immunosuppression.

Neuralstem Cells Induce Significant Functional Improvement In Permanent Rat Spinal Cord Injury, Cell Study Reports

Source: Neuralstem, Inc.
Date: September 13, 2012

Summary;

ROCKVILLE, Md. -- Neuralstem, Inc. announced that its neural stem cells were part of a study, "Long-Distance Growth and Connectivity of Neural Stem Cells After Severe Spinal Cord Injury: Cell-Intrinsic Mechanisms Overcome Spinal Inhibition," published online today in a leading scientific journal CELL. In the study, rats with surgically transected spinal cords, which rendered them permanently and completely paraplegic, were transplanted with Neuralstem's spinal cord stem cells (NSI-566). The study reports that the animals recovered significant locomotor function, regaining movement in all lower extremity joints, and that the transplanted neural stem cells turned into neurons which grew a "remarkable" number of axons that extended for "very long distances" over 17 spinal segments, making connections both above and below the point of severance. These axons reached up to the cervical region (C4) and down to the lumbar region (L1). They also appeared to make reciprocal synaptic connectivity with the host rat spinal cord neurons in the gray matter for several segments below the injury.

Further study showed that re-transecting the spinal cord immediately above the graft abolished the functional gain, indicating that the regeneration of host axons into the human stem cell graft was responsible for the functional recovery. The cells that Neuralstem contributed to the study, NSI-566, are the same cells used in the recently completed Phase 1 clinical trial for the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Neuralstem has also submitted an application to the FDA for a trial to treat chronic spinal cord injury with these cells.

StemCells, Inc. Reports Positive Interim Data From Spinal Cord Injury Trial Cells and Procedure Well Tolerated; Gains in Sensory Function Confirmed

Source: StemCells, Inc.
Date: September 3, 2012

Summary:

NEWARK, Calif. -- StemCells, Inc. today announced that interim six-month data from the first patient cohort in the Company's Phase I/II clinical trial of its proprietary HuCNS-SC® product candidate (purified human neural stem cells) for chronic spinal cord injury continues to demonstrate a favorable safety profile, and shows considerable gains in sensory function in two of the three patients compared to pre-transplant baselines. The third patient remains stable. The data was presented by Armin Curt, M.D., principal investigator for the clinical trial, at the 51st Annual Scientific Meeting of the International Spinal Cord Society in London, England. The trial represents the first time that neural stem cells have been transplanted as a potential therapeutic agent for spinal cord injury.

Patients in the study's first cohort all suffered a complete injury to the thoracic (chest-level) spinal cord. In a complete injury, there is no neurological function below the level of injury. All three patients were transplanted four to nine months after injury with a dose of 20 million cells at the site of injury. The surgery, immunosuppression and the cell transplants have been well tolerated by all the patients. There were no abnormal clinical, electrophysiological or radiological responses to the cells, and all the patients were neurologically stable through the first six months following transplantation. Changes in sensitivity to touch, heat and electrical stimuli were observed in well-defined and consistent areas below the level of injury in two of the patients, while no changes were observed in the third patient. Importantly, tests of perception of different sensory stimuli as well as measures of electrical impulse transmission across the site of injury correlate with the clinical examination, providing independent and objective confirmation of the changes in sensory function.

New Hope For Spinal Cord Injury Patients

Source: Monash University
Date: 29 August 2012

Summary:

A new antibody could reverse the damage caused by trauma to the central nervous system, according to new research. After a neurotrauma event, such as a spinal cord injury, the body produces an inflammatory response that often leads to scarring and permanent nerve damage. There are currently no treatment options.

Research published in The American Journal of Pathology and led by Monash University's Australian Regenerative Medicine Institute (ARMI) and the Centre for Eye Research Australia (CERA) details how a new antibody, created by the US therapeutic antibody company Lpath, blocks the effects of lysophosphatidic acid (LPA). A molecule released in response to injury, LPA promotes inflammation and nerve cell death.

The research team, led by Dr Yona Goldshmit of ARMI and Dr Alice Pébay of CERA, demonstrated that by administering the antibody soon after the injury occurred, it was possible to preserve nerve cells and limit the amount of scarring, while substantially reducing the losses in motor function.

StemCells, Inc. Completes Enrollment of First Cohort in Landmark Chronic Spinal Cord Injury Trial

Source: StemCells, Inc.
Date: December 15, 2011

Summary:

NEWARK, Calif., -- StemCells, Inc. announced today that the first cohort of the Company's Phase I/II clinical trial in chronic spinal cord injury have been successfully transplanted with the Company's proprietary HuCNS-SC® neural stem cells. This landmark clinical trial has a unique design, in which patients with progressively decreasing severity of injury will be treated in three sequential cohorts. The first cohort of patients all have spinal cord injury classified as AIS A, the most severe level identified by the American Spinal Injury Association Impairment Scale (AIS).

Lab Creates Cells Used by Brain to Control Muscle Cells

Source: University of Central Florida
Date: November 22, 2011

Summary:

University of Central Florida researchers, for the first time, have used stem cells to grow neuromuscular junctions between human muscle cells and human spinal cord cells, the key connectors used by the brain to communicate and control muscles in the body. The success at UCF is a critical step in developing “human-on-a-chip” systems. The systems are models that recreate how organs or a series of organs function in the body. Their use could accelerate medical research and drug testing, potentially delivering life-saving breakthroughs much more quickly than the typical 10-year trajectory most drugs take now to get through animal and patient trials. The work, funded through the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health, is described in the December issue of Biomaterials.

Geron Presents Clinical Data Update from GRNOPC1 Spinal Cord Injury Trial

Source: Geron Corporation
Date: October 20, 2011

Summary:

MENLO PARK, Calif., - Geron Corporation today announced two presentations on the company's ongoing Phase 1 clinical trial of its human embryonic stem cell-based therapy, GRNOPC1, in patients with spinal cord injury. Safety data were presented at the Pre-Conference Symposia of the joint 2011 American Congress of Rehabilitation Medicine and American Society of Neuro-Radiology Annual Meeting in Atlanta, GA. A second presentation was given at the Working 2 Walk 2011 conference in Rockville, MD. The presentations were given by Joseph Gold, Ph.D., Geron's Senior Director of Neurobiology and Stem Cell Therapies and Linda Jones, P.T., M.S., Geron's Senior Clinical Trials Manager for GRNOPC1.

Mice stem cells guided into myelinating cells by the trillions

Source: Case Western Reserve University
Date: September 26, 2011

Summary:

Scientists at Case Western Reserve University School of Medicine found a way to rapidly produce pure populations of cells that grow into the protective myelin coating on nerves in mice. Their process opens a door to research and potential treatments for multiple sclerosis, cerebral palsy and other demyelinating diseases afflicting millions of people worldwide. The findings were published in the online issue of Nature Methods, Sunday, Sept. 25.

With this new discovery, scientists are now able to direct mouse stem cells into populations of myelinating cells, called oligodendrocyte progenitor cells, or OPCs. in just 10 days. The team’s success relied upon guiding the cells through specific stages that match those that occur during normal embryonic development.

First, stem cells in a petri dish are treated with molecules to direct them to become the most primitive cells in the nervous system. These cells then organize into structures called neural rosettes reminiscent of the developing brain and spinal cord. To produce OPCs, the neural rosettes are then treated with a defined set of signaling proteins previously known to be important for generation of OPCs in the developing spinal cord.

After this 10 day protocol, the researchers were able to maintain the OPCs in the lab for more than a month by growing them on a specific protein surface called laminin and adding growth factors associated with OPC development. The OPCs were nearly homogenous and could be multiplied to obtain more than a trillion cells. The OPCs were treated with thyroid hormone, which is key to regulating the transition of the OPCs to oligodendrocytes. The result was the OPCs stopped proliferating and turned into oligodendrocytes within four days. Testing on nerves lacking myelin, both on the lab bench and in diseased mouse models, showed the OPCs derived from the process flourished into oligodendrocytes and restored normal myelin within days, demonstrating their potential use in therapeutic transplants.

StemCells, Inc. Announces World's First Neural Stem Cell Transplant in Spinal Cord Injury Patient

Source: StemCells, Inc.
Date: September 22, 2011

Summary:

StemCells, Inc. announced today that the first patient in the Company's breakthrough Phase I/II clinical trial in chronic spinal cord injury was successfully transplanted with the Company's proprietary HuCNS-SC(R) adult neural stem cells. The stem cells were administered yesterday at Balgrist University Hospital, University of Zurich, a world leading medical center for spinal cord injury and rehabilitation. The transplant surgery was performed by a team of surgeons led by Dr. Raphael Guzman, a visiting staff neurosurgeon also on faculty at Department of Neurosurgery, Stanford University, and Dr. K. Min, an orthopedic surgeon at Balgrist University Hospital.

Additional News Coverage of Stanford University Embryonic Stem Cell Trial For Spinal Cord Injury

Below are summaries of additional coverage on the announcement yesterday by Stanford University that a researcher has begun the first test of an embryonic stem cell therapy on the West Coast from the San Jose Mercury News and San Francisco Chronicle:

From the San Jose Mercury News, September 21, 2011:

A Stanford researcher has injected 2 million human embryonic stem cells into the spinal cord of a paralyzed patient at Santa Clara Valley Medical Center, marking the first West Coast effort to test the potential therapy. The experiment, announced Tuesday, is designed only to test safety, but doctors will also note whether it improves sensation or helps the patient regain movement.

From the San Francisco Chronicle, September 21, 2011:

A Bay Area patient who recently suffered a serious spinal cord injury and is now paralyzed from the waist down joined the world's first-ever embryonic stem cell study in humans last week, when Stanford doctors injected 2 million cells designed to replace damaged neurons in the patient's spine.

The patient, who is not being identified, is the fourth person to be enrolled in the clinical trial being run by Menlo Park's Geron Corp. and the first person in California. The patient, whose participation in the trial was revealed Tuesday, received the stem cell injection Saturday at Santa Clara Valley Medical Center and is now at the rehabilitation center there.

The study is not meant to determine whether the stem cells can cure or even improve the patients' condition, but to find out if the treatment itself is safe. Researchers will be monitoring patients over the following months and years to look for side effects, including possible benign tumor growth if the stem cells start to replicate, or adverse immune reactions.

Embryonic stem cell therapy for paralysis given to first patient in western United States

Source: Stanford University School of Medicine
Date: September 20, 2011

Summary:

The Stanford University School of Medicine and Santa Clara Valley Medical Center have enrolled the fourth participant in the nation’s first trial of cells derived from human embryonic stem cells. The phase-1, FDA-approved trial is meant to test the safety of the cells in up to 10 people with recent spinal cord injuries at seven trial sites across the United States.

The most recent patient was treated Sept. 17 at the Rehabilitation Trauma Center at SCVMC with cells prepared for injection at Stanford. Stanford neurosurgeon Gary Steinberg, MD, PhD, implanted the cells. Three other patients have previously received the surgically delivered cells: two at the Shepherd Center in Atlanta beginning in October of last year, and one at Northwestern Memorial Hospital and the Rehabilitation Institute of Chicago in May 2011. The Stanford/SCVMC patient is the first person to receive the therapy west of the Mississippi.

The Palo Alto Weekly and San Francisco Business Times carried news stories on this development today.

NEW CLASS OF STEM CELL-LIKE CELLS DISCOVERED IN SPINAL CORD OFFERS POSSIBILITIES FOR SPINAL CORD REPAIR

Source: The Allen Institute for Brain Science
Date: September 15, 2011

Summary:

The Allen Institute for Brain Science announced today the discovery of a new class of cells in the spinal cord that act like neural stem cells, offering a fresh avenue in the search for therapies to treat spinal cord injury and disease. The published collaborative study, authored by scientists from the University of British Columbia, the Allen Institute for Brain Science and The Montreal Neurological Institute and Hospital at McGill University and titled “Adult Spinal Cord Radial Glia Display a Unique Progenitor Phenotype,” appears in the open access journal PLoS One.

A new program for neural stem cells

Source: Max-Planck-Gesellschaft
Date: May 12, 2011

Summary:

Neural stem cells can do a lot, but not everything. For example, brain and spinal cord cells are not usually generated by neural stem cells of the peripheral nervous system, and it is not possible to produce cells of the peripheral nervous system from the stem cells of the brain. However, researchers from the Max Planck Institute for Brain Research in Frankfurt and the Max Planck Institute of Immunobiology and Epigenetics in Freiburg have now succeeded in producing central nervous system cells from neural stem cells of the peripheral nervous system. They found that if peripheral stem cells are maintained under defined growth conditions, they generate oligodendrocytes, which form the myelin layer that surrounds the neurons found in the brain and spinal cord. The research is published in the Journal of Neuroscience.

Regenerating Nerve Cells: Research Offers Hope in New Treatment for Spinal Cord Injuries

Source: Rutgers University
Date: May 3, 2011

Summary:

Rutgers researchers have developed an innovative new treatment that could help minimize nerve damage in spinal cord injuries, promote tissue healing and minimize pain. After a spinal cord injury there is an increased production of a protein (RhoA) that blocks regeneration of nerve cells that carry signals along the spinal cord and prevents the injured tissue from healing.

Scientists at the W.M. Keck Center for Collaborative Neuroscience and Quark Pharmaceuticals Inc. have developed a chemically synthesized siRNA molecule that decreases the production of the RhoA protein when administered to the spine and allows regeneration of the nerve cells. The study is published in the Journal of Neurotrauma.

First patient to get stem cell therapy comes forward

Source: Washington Post
Posted: April 7, 2011 12:22 AM EDT

Summary:

The Washington Post reports a 21-year-old Alabama nursing student who was paralyzed from the chest down in a car crash in September has come forward to identify himself as the volunteer for a clinical trial using embryonic stem cells sponsored by Geron Corporation and conducted at the Shepherd Center in Atlanta.

Research May Lead to New Treatments for Parkinson’s Disease and Other Neurological Disorders

Source: Marshall University Research Corporation
Date: March 24, 2011

Summary:

Scientists at Marshall University are conducting research that may someday lead to new treatments for repair of the central nervous system. The group has identified and analyzed unique adult animal stem cells that can turn into neurons. The neurons they found appear to have many of the qualities desired for cells being used in development of therapies for slowly progressing, degenerative conditions like Parkinson's disease and Huntington's disease and multiple sclerosis, and for damage due to stroke or spinal cord injury. The research was published in a recent issue of the Journal of Cellular Physiology.

StemCells, Inc. Initiates World's First Neural Stem Cell Trial in Spinal Cord Injury

Source: StemCells, Inc.
Date: March 14, 2011

Summary:

PALO ALTO, Calif., (GlobeNewswire via COMTEX) -- StemCells, Inc. announced today the initiation of a Phase I/II clinical trial of its proprietary HuCNS-SC(R) human neural stem cells in chronic spinal cord injury. This trial is now open for enrollment, and will accrue patients with both complete and incomplete degrees of paralysis who are three to 12 months post-injury. The trial is being conducted in Switzerland at the Balgrist University Hospital, University of Zurich, a world leading medical center for spinal cord injury and rehabilitation, and is being led by Armin Curt, MD, Professor and Chairman, Spinal Cord Injury Center at the University of Zurich, and Medical Director of the Paraplegic Center at the Balgrist University Hospital.

Researchers focus on human cells for spinal cord injury repair: Derived from stem cells – restore movement in animal models

Source: University of Colorado School of Medicine
Date: March 2, 2011

Summary:

AURORA, Colo. - For the first time, scientists discovered that a specific type of human cell, generated from stem cells and transplanted into spinal cord injured rats, provides tremendous benefit, not only repairing damage to the nervous system but helping the animals regain locomotor function as well. The study, published today in the journal PLoS ONE, focuses on human astrocytes – the major support cells in the central nervous system – and indicates that transplantation of these cells represents a potential new avenue for the treatment of spinal cord injuries and other central nervous system disorders. Working together, research teams at the University of Colorado School of Medicine and University of Rochester Medical Center have made a major breakthrough in the use of human astrocytes for repairing injured spinal cords in rats.