Public release date: 13-Sep-2012 [ | E-mail | Share ]

Contact: Debra Kain ddkain@ucsd.edu 619-543-6163 University of California - San Diego

In a study at the University of California, San Diego and VA San Diego Healthcare, researchers were able to regenerate "an astonishing degree" of axonal growth at the site of severe spinal cord injury in rats. Their research revealed that early stage neurons have the ability to survive and extend axons to form new, functional neuronal relays across an injury site in the adult central nervous system (CNS).

The study also proved that at least some types of adult CNS axons can overcome a normally inhibitory growth environment to grow over long distances. Importantly, stem cells across species exhibit these properties. The work will be published in the journal Cell on September 14.

The scientists embedded neural stem cells in a matrix of fibrin (a protein key to blood clotting that is already used in human neuron procedures), mixed with growth factors to form a gel. The gel was then applied to the injury site in rats with completely severed spinal cords.

"Using this method, after six weeks, the number of axons emerging from the injury site exceeded by 200-fold what had ever been seen before," said Mark Tuszynski, MD, PhD, professor in the UC San Diego Department of Neurosciences and director of the UCSD Center for Neural Repair, who headed the study. "The axons also grew 10 times the length of axons in any previous study and, importantly, the regeneration of these axons resulted in significant functional improvement."

In addition, adult cells above the injury site regenerated into the neural stem cells, establishing a new relay circuit that could be measured electrically. "By stimulating the spinal cord four segments above the injury and recording this electrical stimulation three segments below, we detected new relays across the transaction site," said Tuszynski.

To confirm that the mechanism underlying recovery was due to formation of new relays, when rats recovered, their spinal cords were re-transected above the implant. The rats lost motor function confirming formation of new relays across the injury.

The grafting procedure resulted in significant functional improvement: On a 21-point walking scale, without treatment, the rats score was only 1.5; following the stem cell therapy, it rose to 7 a score reflecting the animals' ability to move all joints of affected legs.

Results were then replicated using two human stem cell lines, one already in human trials for ALS. "We obtained the exact results using human cells as we had in the rat cells," said Tuszynski.

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Neural stem cells regenerate axons in severe spinal cord injury

(CNN) About 37 million Americans have some level of hearing problem, and science hasnt come up with a perfect solution to restore this valuable sense.

Help may be on the way, at least in theory. A team of researchers reports in the journal Nature that they have used embryonic stem cells to restore some hearing in impaired gerbils. But more investigation is necessary before the technology can move to humans.

Background

Everyone has two main sensory cell types associated with hearing: the hair cell and the auditory neuron. Hair cells take sound and make it into an electrical signal. Neurons pick up the signal and transfer it to the brain, so you know what youre hearing.

Most deafness is caused by a problem in one or both of these cells, said Marcelo Rivolta, senior author of the study and stem cell biologist at the University of Sheffield, United Kingdom. The cells are usually created during the embryonic stage of development.

Adult mammals have lost the ability to replace these cells, Rivolta said. In other words, if these cells are damaged, you cant naturally grow them back.

Cochlear implants are electronic devices designed for people with hearing loss, but they dont work well in people with auditory nerve damage, Rivolta said.

How they did it

Researchers used a drug to chemically damage the auditory nerve in gerbils, creating a condition that would be called auditory neuropathy.

To see if hearing could be brought back, researchers used human embryonic stem cells, and applied biological factors to them that the human body would naturally use in its development. This coaxed them into becoming otic progenitor cells, which can differentiate into cells that function as hair cells and auditory neurons.

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Stem Cells Help Deaf Gerbils Hear

ROCKVILLE, Md., Sept. 13, 2012 /PRNewswire/ --Neuralstem, Inc. (NYSE MKT: CUR) 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 (http://www.cell.com/current). 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.

(Logo: http://photos.prnewswire.com/prnh/20061221/DCTH007LOGO )

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.

"This study demonstrates that our neural stem cells can induce regeneration of injured spinal cord axons into the graft and serve as a bridge to reconnect to gray matter motor neurons for many spinal cord segments below the injury," said Karl Johe, PhD, Chairman of Neuralstem's Board of Directors and Chief Scientific Officer. "This is important in spinal cord injury because the nerve connections below the point of injury die, causing paralysis. Our cells built a bridge that received inputs from regenerating rat axons above the injury. They also sent out new human axons which made new synaptic connections with the host motor neurons in the gray matter below the injury. The fact that these cells induce regeneration of axons and partial recovery of motor function makes them relevant for testing for the treatment of human spinal cord injury."

About the Study

In a study of 12 rats, all 12 underwent complete spinal transections at vertebrae, T3. Six of these were subsequently transplanted with Neuralstem spinal cord stem cells (NSI-566) seven days after the injury. This group was assessed over the next seven weeks and compared to the control group, which had not received transplants. The transplanted rats exhibited significant locomotor recovery, regaining movement in all lower extremity joints. A majority of the grafted cells (57%) turned into neurons. From these, the study reported, a remarkable number of axons emerged, extending both above and below the point of spinal cord lesion. These axons expressed synaptic proteins in the host gray matter, which suggests they made synaptic contact with the host spinal neurons.

About Neuralstem

Neuralstem's patented technology enables the ability to produce neural stem cells of the human brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glia. Neuralstem has recently completed an FDA-approved Phase I safety clinical trial for amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig's disease, and has been awarded orphan status designation by the FDA.

In addition to ALS, the company is also targeting major central nervous system conditions with its NSI-566 cell therapy platform, including spinal cord injury, ischemic spastic paraplegia and chronic stroke. The company has submitted an IND (Investigational New Drug) application to the FDA for a Phase I safety trial in spinal cord injury.

Neuralstem also has the ability to generate stable human neural stem cell lines suitable for the systematic screening of large chemical libraries. Through this proprietary screening technology, Neuralstem has discovered and patented compounds that may stimulate the brain's capacity to generate new neurons, possibly reversing the pathologies of some central nervous system conditions. The company is in a Phase Ib safety trial evaluating NSI-189, its first neurogenic small molecule compound, for the treatment of major depressive disorder (MDD).Additional indications could include chronic traumatic encephalopathy (CTE), Alzheimer's disease, and post-traumatic stress disorder (PTSD).

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

A novel treatment using human embryonic stem cells has successfully restored some hearing to previously deaf gerbils, according to a study published this week in the journal Nature.

Hearing loss is generally caused by the interruption of two different types of cells: The loss of hair cells in the ear, which transform vibrations into electrical signals, and loss of the auditory nerve, which transmits the signals detected by the hair cells to the brainstem. While cochlear implants have proven effective in restoring hearing in cases of hair cell damage, no such treatment has existed for the roughly 10% cases in which the auditory nerve itself is damaged.

The new strategy, designed by Marcelo Rivolta and his team at the University of Sheffield, uses techniques the group has recently developed to coax human embryonic stem cells to differentiate into what are called "otic progenitor cells" -- cells that have the possibility to develop further into either hair cells or auditory nerve cells. The progenitor cells are then transplanted into the ears of gerbils with damaged auditory nerves, and allowed to differentiate further. Gerbils were used in the experiment because they hear a similar range of sounds as humans do.

At that point, the researchers held their breath, hoping that the cells would integrate themselves with the existing infrastructure and take their place in the chain of sensory signaling between the hair cells and the brainstem. In nearly all cases, the scientists could clearly see under the microscope that the new cells had targeted the right spots, reconnecting the hair cells to the brainstem.

But the ultimate test is hearing itself. To test this, the researchers used a standard approach called auditory-evoked responses, which are detected in the brainstem and provide a clear verdict of whether or not sound is being successfully transmitted to the brain.

Control animals with their auditory nerves knocked out did not recover during the experiment -- in order for a sound to register an auditory-evoked response in the brainstem, the control animals basically had to be at a rock concert, requiring a 76-decibel sound. But in the treated animals, that number dropped to 50 decibels on average, and in some animals approached the levels of animals whose hearing was never damaged at all. The strength of the effect was akin to suddenly being able to hear someone talking while previously not being able to hear them yell.

The researchers hope that their method will spark a new interest in using stem cells to treat hearing loss in people, though much work needs to be done before that is a real possibility. Hurdles include developing a surgical technique to access the appropriate part of the ear in people, and ensuring that the treatment sticks over long periods of time.

Nevertheless, the scientists are optimistic that the approach can be directly translated to humans with hearing loss, finally allowing people who cannot benefit from a cochlear implant to hear again.

You can read a summary of the paper here.

Return to the Science Now blog.

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Stem cell treatment restores hearing in gerbils

Published: Sept. 13, 2012 at 5:41 PM

SHEFFIELD, England, Sept. 13 (UPI) -- British scientists said human embryonic stem cells were used to treat a common form of hearing loss and could be helpful in treating deafness.

Dr. Marcelo Rivolta of the University of Sheffield transplanted human embryonic stem cells into deaf gerbils and obtained a functional recovery of, on average, around 46 percent.

The improvement was evident about four weeks after administering the cells, Rivolta said.

"We believe this an important step forward. We have now a method to produce human cochlear sensory cells that we could use to develop new drugs and treatments, and to study the function of genes," Rivolta said in a statement. "And more importantly, we have the proof-of-concept that human stem cells could be used to repair the damaged ear."

The model of hearing loss successfully treated by the scientists was similar to a human condition known as auditory neuropathy -- a form of deafness in which the damage occurs at the level of the cochlear nerve -- involving 15 percent of the population worldwide with profound hearing loss.

The findings were published in the journal Nature.

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Stem cells could help treat deafness

Connie K. Ho for redOrbit.com Your Universe Online

A group of researchers from the United Kingdom who worked with deaf gerbils were recently able to give the animals the ability to hear again. The study is the first of its kind to replace damaged nerve cells with stem cells.

The study, published recently in the journal Nature, discovered that hearing can improve when nerves were placed in the ear of the gerbils. Gerbils were the focus of the study as they have a hearing range similar to that of humans. The researchers believe that, even with these new findings, it will still be difficult to treat humans who have a hearing disability.

The research is tremendously encouraging and gives us real hope that it will be possible to fix the actual cause of some types of hearing loss in the future, remarked Ralph Holme, head of biomedical research for the charity Action on Hearing Loss, in an article by the BBC. For the millions of people for whom hearing loss is eroding their quality of life, this cant come soon enough.

According to the BBC, activities like listening to the radio or chatting with a friend require a change of sounds waves in the air to electrical signals; these messages are sent to the brain to be deciphered and occur with the help of tiny hairs in the inner ear. With one in 10 people who have extensive hearing loss have nerve cells that are damaged, scientists from the University of Sheffield worked to replace the spiral ganglion neurons with new nerve cells.

It is a big moment, it really is a major development, mentioned David Moore, the director of the Medical Research Councils Institute of Hearing Research, in the BBC article. The biggest issue is actually getting into the part of the inner ear where theyll do some good. Its extremely tiny and very difficult to get to and that will be a really formidable undertaking.

The researchers targeted deafness related to neurons of the auditory nerve, as opposed to deafness from damaged hair cells that can be overcome by cochlear implants.

We have concentrated on trying to fix the problem at the neuronal level. The cochlear implant is a device that functionally replaces the hair cell it takes sound and transforms it into an electrical signal, noted Dr. Marcelo Rivolta, a researcher at the University of Sheffield, in a U.S. News article. But for the cochlear implant to work, you have to have a good connection to the brain.

In the study, the stem cells were taken from a human embryo to be cultured in a test tube. The researchers then added a mix of chemicals to the stem cells, changing them into cells that were like the spiral ganglion neurons and injected into the inner ears of 18 gerbils that were deafened with a drug that damaged their auditory nerves. The group of investigators measured the improvement in hearing by tracking the brainwaves. The study took place over a ten-week period, with the gerbils demonstrating an average improvement of 45 percent in hearing range. Some gerbils had much success, with hearing improving up to 90 percent, while a little under a third of the gerbils did not have any response to the treatment.

It would mean going from being so deaf that you wouldnt be able to hear a lorry or truck in the street to the point where you would be able to hear a conversation, remarked Rivolta in an article by the BBC. It is not a complete cure, they will not be able to hear a whisper, but they would certainly be able to maintain a conversation in a room.

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Stem Cells Replace Damaged Nerve Cells In Inner Ear