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.

Stem Cell-Derived Dopaminergic Neurons Rescue Motor Defects in Parkinsonian Monkeys

Source: Journal of Clinical Investigation

Date December 3, 2012

 Researchers have derived dopaminergic neurons from bone marrow stem cells in monkeys.

Parkinson's disease is a degenerative disorder of the central nervous system that is characterized by tremors, rigidity, slowness of movement, and difficulty walking. It is caused by loss of the neurons that produce the neurotransmitter dopamine (known as dopaminergic neurons). One of the primary goals in Parkinson's disease research is to develop a replacement for dopaminergic neurons.

In a new study, researchers led by Takuya Hayashi at the RIKEN Center for Molecular Imaging Science in Kobe, Japan, derived dopaminergic neurons from bone marrow stem cells in monkeys. The cells were retrieved during a standard bone marrow aspiration and then treated with growth factors that directed the stem cells to become dopaminergic neurons. The monkeys that donated the stem cells were treated with a chemical to induce Parkinson's disease and then received a transplant of the new dopaminergic neurons that had been derived from their own bone marrow stem cells. Monkeys that received the transplant showed significant improvement in motor defects.

This study demonstrates that dopaminergic neurons derived from adult bone marrow stem cells can be safely used to improve motor function in Parkinson's disease in monkeys.

The research is published in the Journal of Clinical Investigation.

Neurons Made from Stem Cells Drive Brain Activity After Transplantation in Laboratory Model

Source: Sanford-Burnham Medical Research Institute

Date: November 15, 2012

Summary:

Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer's disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network.

The study was published November 7 in the Journal of Neuroscience.

Scientists Pinpoint Key Player in Parkinson's disease neuron loss Stem cell study may help to unravel how a genetic mutation leads to Parkinson's Symptoms

Source: Salk Institute for Biological Studies
Date: October 19, 2012

LA JOLLA, CA—By reprogramming skin cells from Parkinson's disease patients with a known genetic mutation, researchers at the Salk Institute for Biological Studies have identified damage to neural stem cells as a powerful player in the disease. The findings, reported online October 17, 2012 in Nature, may lead to new ways to diagnose and treat the disease.

The scientists found that a common mutation to a gene that produce the enzyme LRRK2, which is responsible for both familial and sporadic cases of Parkinson's disease, deforms the membrane surrounding the nucleus of a neural stem cell. Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons, such as the ones that respond to dopamine.

The Salk researchers found that a common genetic mutation involved in Parkinson's disease deforms the membranes (green) surrounding the nuclei (blue) of neural stem cells. The discovery may lead to new ways to diagnose and treat the disease.

StemCells, Inc. Announces First Transplant of Neural Stem Cells Into Patient in Clinical Trial for Dry Age-Related Macular Degeneration

Source: StemCells, Inc.
Date: October 4, 2012

 Summary:

 NEWARK, Calif. -- StemCells, Inc. today announced that the first patient in its Phase I/II clinical trial in dry age-related macular degeneration (AMD) has been enrolled and transplanted. The trial is designed to evaluate the safety and preliminary efficacy of the Company's proprietary HuCNS-SC® product candidate (purified human neural stem cells) as a treatment for dry AMD, and the patient was transplanted with the cells yesterday at the Retina Foundation of the Southwest (RFSW) in Dallas, Texas, one of the leading independent vision research centers in the United States. AMD afflicts approximately 30 million people worldwide and is the leading cause of vision loss and blindness in people over 55 years of age.

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.

Astrocytes Control the Generation of New Neurons from Neural Stem Cells

Source: University of Gothenburg
Date: 22 August 2012

Summary:

Researchers from the Laboratory of astrocyte biology and CNS regeneration headed by Prof. Milos Pekny at the University of Gothenburg just published a research article in a journal Stem Cells on the molecular mechanism that controls generation of new neurons in the brain. Astrocytes are cells that have many functions in the central nervous system, such as the control of neuronal synapses, blood flow, or the brain's response to neurotrauma or stroke.

Reduces brain tissue damage
Prof. Pekny's laboratory together with collaborators have earlier demonstrated that astrocytes reduce the brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.

Generation of new neurons
In their current study, the Sahlgrenska Academy researchers show how astrocytes control the generation of new neurons in the brain. An important contribution to this project came from Åbo Academy, one of Sahlgrenska's traditional collaborative partners.

Neuroscientists Find Brain Stem Cells that May Be Responsible for Higher Functions, Bigger Brains

Source: The Scripps Research Institute
Date: August 7, 2012

Summary:

Scientists from The Scripps Research Institute have identified a new stem cell population that may be responsible for giving birth to the neurons responsible for higher thinking. The finding also paves the way for scientists to produce these neurons in culture -- a first step in developing better treatments for cognitive disorders, such as schizophrenia and autism, which result from disrupted connections among these brain cells. Published in the August 10, 2012 issue of the journal Science, the new research reveals how neurons in the uppermost layers of the cerebral cortex form during embryonic brain development.

Brain's Stem Cells 'Eavesdrop' to Find out When to Act

Source: Johns Hopkins Medicine
Date: August 6, 2012

Summary:

Working with mice, Johns Hopkins researchers say they have figured out how stem cells found in a part of the brain responsible for learning, memory and mood regulation decide to remain dormant or create new brain cells. Apparently, the stem cells "listen in" on the chemical communication among nearby neurons to get an idea about what is stressing the system and when they need to act.

The researchers say understanding this process of chemical signaling may shed light on how the brain reacts to its environment and how current antidepressants work, because in animals these drugs have been shown to increase the number of brain cells. The findings are reported July 29 in the advance online publication of Nature.

New Treatment Target for Deadly Brain Tumors

Source: University of Texas Southwestern Medical Center
Date: August 1, 2012

Summary:

A study by UT Southwestern Medical Center researchers published August 1 in Nature reveals new insight into why the most common, deadly kind of brain tumor in adults recurs and identifies a potential target for future therapies.

Glioblastoma multiforme (GBM) currently is considered incurable. Despite responding to initial therapy, the cancer almost always returns. GBM is a fast-growing, malignant brain tumor that occurred in 15 percent of the estimated 22,000 Americans diagnosed with brain and nervous system tumors in 2010. The median survival rate is about 15 months, according to the National Cancer Institute. Using a genetically engineered mouse model of GBM, the researchers found that the resting tumor cells act more like stem cells -- the non-cancerous cells the body uses to repair and replenish itself,

Researchers Turn Skin Cells into Brain Cells, A Promising Path To Better Parkinson's Treatment

Source: Johns Hopkins Medicine
Date: July 17, 2012

Summary:

Using adult stem cells, Johns Hopkins researchers and a consortium of colleagues nationwide say they have generated the type of human neuron specifically damaged by Parkinson’s disease (PD) and used various drugs to stop the damage. Their experiments on cells in the laboratory, reported in the July 4 issue of the journal Science Translational Medicine, could speed the search for new drugs to treat the incurable neurodegenerative disease, but also, they say, may lead them back to better ways of using medications that previously failed in clinical trials.

StemCells, Inc. Announces Its Human Neural Stem Cells Restore Memory in Models of Alzheimer's Disease

Source: StemCells, Inc.
Date: July 17, 2012

Summary:

StemCells, Inc. today announced preclinical data demonstrating that its proprietary human neural stem cells restored memory and enhanced synaptic function in two animal models relevant to Alzheimer's disease (AD). The data was presented today at the Alzheimer's Association International Conference 2012 in Vancouver, Canada.

The study results showed that transplanting the cells into a specific region of the brain, the hippocampus, statistically increased memory in two different animal models. The hippocampus is critically important to the control of memory and is severely impacted by the pathology of AD. Specifically, hippocampal synaptic density is reduced in AD and correlates with memory loss. The researchers observed increased synaptic density and improved memory post transplantation. Importantly, these results did not require reduction in beta amyloid or tau that accumulate in the brains of patients with AD and account for the pathological hallmarks of the disease.

Common Diabetes Drug Promotes Development of Brain Stem Cells

Source: The Hospital for Sick Children (SickKids)
Date: July 5, 2012

Summary:

TORONTO – Researchers at The Hospital for Sick Children (SickKids) have found that metformin, a drug commonly used to treat Type II diabetes, can help trigger the pathway used to instruct stem cells in the brain to become neural (nerve) cells. Brain stem cells and the neural cells they generate play a role in the repair of the injured or degenerating brain. This study suggests a novel therapeutic approach to treating people with brain injuries or potentially even neurodegenerative diseases. The study – led by Dr. Freda Miller, Senior Scientist at SickKids and Professor in the Department of Molecular Genetics at the University of Toronto – is published in the July 5 advance online edition of Cell Stem Cell.

Patient-derived Stem Cells Could Improve Drug Research for Parkinson's

Source: National Institute of Neurological Disorders and Stroke
Date: July 4, 2012

Summary:

Researchers have taken a step toward personalized medicine for Parkinson's disease, by investigating signs of the disease in patient-derived cells and testing how the cells respond to drug treatments. The study was funded by the National Institutes of Health.

The researchers collected skin cells from patients with genetically inherited forms of Parkinson’s and reprogrammed those cells into neurons. They found that neurons derived from individuals with distinct types of Parkinson's showed common signs of distress and vulnerability – in particular, abnormalities in the cellular energy factories known as mitochondria. At the same time, the cells' responses to different treatments depended on the type of Parkinson's each patient had.

The results were published in Science Translational Medicine.

Turning Skin Cells Into Brain Cells: Huntington's Disease in a Dish

Source: Johns Hopkins Medical Institutions
Date: June 28, 2012

Summary:

Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntington's disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

To conduct their experiment, researchers took a skin biopsy from a patient with very early onset HD.When seen by Ross at the HD Center at Hopkins, the patient was just seven years old. She had a very severe form of the disease, which rarely appears in childhood, and of the mutation that causes it. Using cells from a patient with a more rapidly progressing form of the disease gave Ross' team the best tools with which to replicate HD in a way that is applicable to patients with all forms of HD.

Her skin cells were grown in culture and then reprogrammed in a lab into induced pluripotent stem cells. Scientists converted those cells into generic neurons and then into medium spiny neurons. What they found was that the medium spiny neurons deriving from HD cells behaved just as they expected medium spiny neurons from an HD patient would. They showed rapid degeneration when cultured in the lab using basic culture medium without extensive supporting nutrients. By contrast, control cell lines did not show neuronal degeneration.

The research, published in the journal Cell Stem Cell, is the work of a Huntington's Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups.

Scientists Reprogram Skin Cells Into Brain Cells

Source: Gladstone Institutes
Date: June 7, 2012

Summary:

Scientists at the Gladstone Institutes have for the first time transformed skin cells -- with a single genetic factor -- into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation -- or reprogramming -- of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

This research comes at a time of renewed focus on Alzheimer's disease, which currently afflicts 5.4 million people in the United States alone -- a figure expected to nearly triple by 2050. Yet there are no approved medications to prevent or reverse the progression of this debilitating disease.

In findings appearing online June 7 in Cell Stem Cell, researchers describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.