Source: BioTime, Inc.
Date: January 7, 2013

ALAMEDA, Calif.--(BUSINESS WIRE)--BioTime, Inc. (NYSE MKT: BTX) and its recently formed subsidiary BioTime Acquisition Corporation (BAC) jointly announced today that they have entered into a definitive Asset Contribution Agreement with Geron Corporation (Nasdaq: GERN) to acquire the intellectual property, including patents and patent applications, and other assets related to Geron’s human embryonic stem (hES) cell programs consistent with the financial terms outlined in the letter of intent announced on November 15, 2012.

Under the definitive agreement, Geron will contribute to BAC intellectual property, certain cell lines and other assets, including the Phase 1 clinical trial of hES cell-derived oligodendrocytes in patients with acute spinal cord injury, and Geron’s autologous cellular immunotherapy program. BioTime will contribute to BAC $5 million in cash, 8,902,077 BioTime common shares to be held by BAC, five-year warrants to purchase 8,000,000 common shares of BioTime at a price of $5.00 per share (“BioTime Warrants”), rights to use certain clinical grade hES cell lines, a sublicense to use certain patents for stem cell differentiation technology, and minority stakes in two of BioTime’s subsidiaries, OrthoCyte Corporation and Cell Cure Neurosciences Ltd. BAC will also pay to Geron royalties on the sale of products that are commercialized, if any, in reliance upon Geron patents contributed or licensed to BAC. A private investor has also agreed to provide an equity investment of $5 million in BAC and a $5 million equity investment in BioTime in conjunction with the transaction.

Geron pioneered the field of regenerative medicine in the mid-1990s by organizing the first effort to isolate human embryonic stem (hES) cells. hES cells are early-stage stem cells that are capable of becoming all of the cell types in the human body, and therefore are widely recognized as a means of manufacturing cells that are potentially useful in regenerating tissue function for a wide array of degenerative diseases. Currently, Geron’s hESC patent portfolio includes over 400 patents and patent applications that will be transferred or sublicensed to BAC. Geron obtained the first approval from the Food and Drug Administration for human clinical trials of a product manufactured from hES cells.

Geron’s former hES cell programs included oligodendrocyte progenitor cells for central nervous system disorders, cardiomyocytes for heart disease, pancreatic islet cells for diabetes, dendritic cells as an immunotherapy vehicle, and chondrocytes for cartilage repair. BAC may pursue the development of therapeutic products from some or all of these cell types, depending upon a number of factors, including the expected cost of development, sufficiency of financing, the state of development of the technology acquired, regulatory considerations, anticipated market size, and competition from other companies in the applicable fields. BAC may also seek to develop other therapeutic products, taking into account the same or other applicable considerations.

“Our consistent goal at BioTime has been to consolidate the pluripotent stem cell technology platform,” stated Michael West, Ph.D., Chief Executive Officer of BioTime, Inc. “With this contribution of assets, the combined intellectual property estate in the BioTime family of companies will be among the strongest in the field of Regenerative Medicine; establishing our leadership in the industry and advancing product development.”

“We are excited about our approach toward consolidating the most important technologies in Regenerative Medicine,” said Thomas Okarma, M.D., Ph.D., president and CEO of BAC. “Regenerative Medicine holds great promise for patients and now, with our significant collection of world class stem cell technologies, IP, and experienced management, we are positioned to help realize that promise.”

Closing of the transactions under the definitive agreement is subject to certain negotiated closing conditions, including the registration of the BAC Series A common stock, the BioTime common shares contributed to BAC, and the BioTime Warrants under the Securities Act of 1933, as amended, and certain approvals by BioTime shareholders. The transaction is expected to close no later than September 30, 2013.

Upon closing of the transaction, Geron will receive BAC Series A common stock, and BioTime and the private investor will receive BAC Series B common stock in the transaction. The Series A and Series B common stock will be identical, except that BAC will be entitled to make certain distributions or pay dividends on its Series A common stock without making a distribution or paying a dividend on its Series B common stock.

Following the closing of the transaction, Geron will distribute on a pro rata basis to its stockholders the shares of BAC Series A common stock received in the transaction. Following that distribution by Geron, BAC will distribute on a pro rata basis to the holders of those shares the BioTime Warrants. The Series B common stock will be convertible into Series A common stock following the distribution of the BioTime Warrants.

Following these distributions, BioTime will own approximately 71.6%, Geron stockholders will own approximately 21.4%, and the private investor will own approximately 7.0%, of the outstanding BAC common stock. BioTime and the private investor will also receive warrants to purchase additional shares of BAC Series B common stock that would enable them to increase their collective ownership in BAC by approximately 2.2%, which would reduce the Geron stockholders’ ownership in BAC to approximately 19.2%.

BAC plans to seek to list its Series A common stock, and BioTime intends to seek to list the BioTime Warrants, on a national securities exchange.

In anticipation of use by BAC, BioTime is entering into a three-year lease of an office and research facility in Menlo Park, Calif.

In a separate and related transaction, BioTime and BAC have each entered into Stock and Warrant Purchase Agreements with a private investor to provide each company with $5 million in equity financing. Under the terms of the BioTime agreement, the investor will invest $5 million in BioTime by purchasing an aggregate of 1,350,000 BioTime common shares at a purchase price of approximately $3.70 per share and warrants to purchase 650,000 additional BioTime common shares with an exercise price of $5.00 per share and a three year term. The shares and warrants will be sold to the investor in two tranches. In the first tranche, the investor will purchase 540,000 BioTime common shares and warrants to purchase approximately 260,000 BioTime common shares for $2 million subject to the conditions of the Stock and Warrant Purchase Agreement. The second BioTime investment tranche of $3 million will be funded in conjunction with the closing of the stem cell asset transaction with Geron. Closing of the second tranche of the share and warrant purchase is subject to certain additional conditions; these conditions include the closing of the stem cell asset transaction. This $5 million investment will be used to fund BioTime’s $5 million cash contribution to BAC.

Under the terms of its Stock Purchase Agreement with BAC, the investor will contribute $5 million in cash to BAC in exchange for 2,136,000 shares of BAC Series B common stock that, upon issuance, will represent approximately 7% of the BAC common stock outstanding at the closing, plus warrants to purchase approximately 350,000 additional shares of BAC Series B common stock at an exercise price of $5.00 per share, with a three year term. Closing of the financing in BAC will occur in conjunction with the closing of the stem cell asset transaction with Geron, and is subject to certain conditions, including the closing of the stem cell asset transaction.

Kaye Scholer LLP and Thompson, Welch, Soroko & Gilbert LLP are acting as legal counsel to BioTime in connection with the transaction.

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

NEWARK, Calif., Sept. 3, 2012 (GLOBE NEWSWIRE) -- StemCells, Inc. (Nasdaq:STEM) 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.

"As with the three-month assessments, these three patients have tolerated the cell transplantation very well, and we have no safety concerns at this point," said Dr. Curt, Professor and Chairman of the Spinal Cord Injury Center at Balgrist University Hospital, University of Zurich. "We are very intrigued to see that two of the three patients have gained considerable sensory function. The gains in sensation have evolved in a progressive pattern below the level of injury and are unanticipated in spinal cord injury patients with this severity of injury, suggesting that the neural stem cells are having a beneficial clinical effect. Sensory function of all these patients was stable before transplantation, so the reappearance of sensation is rather unexpected."   

Stephen Huhn, M.D., FACS, FAAP, Vice President and Head of the CNS Program at StemCells, added, "To see this kind of change in patients who truly have the worst-of-the-worst type of injury to the spinal cord is very exciting.  To our knowledge, this is the first time a sensory change of this magnitude has been reported in patients with complete spinal cord injury following a stem cell transplantation.  We clearly need to collect more data to establish efficacy, but we are encouraged. We are pushing ahead with our trial and plan to dose the first patient with an incomplete injury soon."

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.

Conference Call

StemCells will host a live conference call and webcast, which will include Dr. Curt, on Tuesday, September 4, at 11:30 a.m. Eastern Time (8:30 a.m. Pacific Time) to discuss the summary of the data.  Interested parties are invited to listen to the call over the Internet via the Investors section of the Company's website at http://investor.stemcellsinc.com/phoenix.zhtml?c=86230&p=irol-irhome. An archived version of the webcast will be available for replay on the Company's website beginning approximately two hours following the conclusion of the live call and continuing for a period of 30 days.

About the Spinal Cord Injury Clinical Trial           

The Phase I/II clinical trial of StemCells, Inc.'s HuCNS-SC® purified human adult neural stem cells is designed to assess both safety and preliminary efficacy. Twelve patients with thoracic (chest-level) neurological injuries at the T2-T11 level are planned for enrollment, and their injuries must have occurred within three to twelve months prior to transplantation of the cells.  In addition to assessing safety, the trial will assess preliminary efficacy based on defined clinical endpoints, such as changes in sensation, motor function and bowel/bladder function.  The Company has dosed the first three patients, all of whom have injuries classified as AIS A, in which there is no neurological function below the injury level. The injuries are classified according to the American Spinal Injury Association Impairment Scale (AIS). The second and third cohorts will be patients classified as AIS B and AIS C, those with less severe injury, in which there is some preservation of sensory or motor function.

All patients will receive HuCNS-SC cells through direct transplantation into the spinal cord and will be temporarily immunosuppressed. Patients will be evaluated regularly in the post-transplant period in order to monitor and assess the safety of the HuCNS-SC cells, the surgery and the immunosuppression, as well as to measure any recovery of neurological function below the injury site. The Company intends to follow the effects of this therapy long-term, and each of the patients will be invited to enroll into a separate four year observational study after completing the Phase I/II study.

The trial is being conducted at Balgrist University Hospital, University of Zurich, a world leading medical center for spinal cord injury and rehabilitation, and is open for enrollment to patients in Europe, Canada and the United States. Enrollment for the second cohort is now underway. If you believe you may qualify and are interested in participating in the study, please contact the study nurse either by phone at +41 44 386 39 01 or by email at stemcells.pz@balgrist.ch.

Additional information about the Company's spinal cord injury program can be found on the StemCells, Inc. website at http://www.stemcellsinc.com/Therapeutic-Programs/Clinical-Trials.htm and at http://www.stemcellsinc.com/Therapeutic-Programs/Spinal-Cord-Injury.htm, including video interviews with Company executives and independent collaborators.

Source: Monash University
Date: 29 August 2012

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.

Dr Goldshmit said the study reinforced earlier research on the role of LPA after an injury.

"By blocking the effects of LPA, we can help nerve cells survive a traumatic injury and this will hopefully lead to better outcomes for patients in the future,” Dr Goldshmit said.

Dr Pébay, Head of CERA’s Neuroregeneration Unit, said the study offered great hope for a future pharmacological therapy for spinal cord injuries in humans.

“Perhaps this drug will one day be administered in the back of an ambulance, as the patient is being transported to hospital,” Dr Pébay said. 

The research has been funded by the Transport Accident Commission (TAC) and the National Health and Medical Research Council (NHMRC).

The TAC’s CEO Janet Dore said that each year on average, the TAC accepted 25 new claims for people with spinal cord injuries, both quadriplegia and paraplegia.

“These people will need rehabilitation and medical support from the TAC across their lifetime. Research like this gives us hope that many traumatic spinal injuries could be avoided in the future,” Ms Amies said.

Collaborators in the study included scientists at the O’Brien Institute, Lpath Inc and Melbourne University. 

Source: École Polytechnique Fédérale de Lausanne
Date: 31 May 2012



Scientists wake up a dormant spinal column and restore voluntary lower body movement when stimulated.

Rats with spinal cord injuries and severe paralysis are now walking (and running) thanks to researchers at EPFL. Published in the June 1, 2012 issue of Science, the results show that a severed section of the spinal cord can make a comeback when its own innate intelligence and regenerative capacity is awakened. The study, begun five years ago at the University of Zurich, points to a profound change in our understanding of the central nervous system. According to lead author Grégoire Courtine, it is yet unclear if similar rehabilitation techniques could work for humans, but the observed nerve growth hints at new methods for treating paralysis.

“After a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical-chemical stimulation, our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles when stimulated,” explains Courtine, who holds the International Paraplegic Foundation (IRP) Chair in Spinal Cord Repair at EPFL.

Waking up the spinal cord
It is well known that the brain and spinal cord can adapt and recover from moderate injury, a quality known as neuroplasticity. But until now the spinal cord expressed so little plasticity after severe injury that recovery was impossible. Courtine’s research proves that, under certain conditions, plasticity and recovery can take place in these severe cases—but only if the dormant spinal column is first woken up.

To do this, Courtine and his team injected a chemical solution of monoamine agonists into the rats. These chemicals trigger cell responses by binding to specific dopamine, adrenaline, and serotonin receptors located on the spinal neurons. This cocktail replaces neurotransmitters released by brainstem pathways in healthy subjects and acts to excite neurons and ready them to coordinate lower body movement when the time is right.

Five to 10 minutes after the injection, the scientists electrically stimulated the spinal cord with electrodes implanted in the outermost layer of the spinal canal, called the epidural space. “This localized epidural stimulation sends continuous electrical signals through nerve fibers to the chemically excited neurons that control leg movement. All that is left was to initiate that movement,” explains Rubia van den Brand, contributing author to the study.

The innate intelligence of the spinal column
In 2009, Courtine already reported on restoring movement, albeit involuntary. He discovered that a stimulated rat spinal column—physically isolated from the brain from the lesion down—developed in a surprising way: It started taking over the task of modulating leg movement, allowing previously paralyzed animals to walk over treadmills. These experiments revealed that the movement of the treadmill created sensory feedback that initiated walking—the innate intelligence of the spinal column took over, and walking essentially occurred without any input from the rat’s actual brain. This surprised the researchers and led them to believe that only a very weak signal from the brain was needed for the animals to initiate movement of their own volition.

To test this theory, Courtine replaced the treadmill with a device that vertically supported the subjects, a mechanical harness did not facilitate forward movement and only came into play when they lost balance, giving them the impression of having a healthy and working spinal column. This encouraged the rats to will themselves toward a chocolate reward on the other end of the platform. “What they deemed willpower-based training translated into a fourfold increase in nerve fibers throughout the brain and spine—a regrowth that proves the tremendous potential for neuroplasticity even after severe central nervous system injury,” says Janine Heutschi, co-author in the study.

First human rehabilitation on the horizon
Courtine calls this regrowth “new ontogeny,” a sort of duplication of an infant’s growth phase. The researchers found that the newly formed fibers bypassed the original spinal lesion and allowed signals from the brain to reach the electrochemically-awakened spine. And the signal was sufficiently strong to initiate movement over ground—without the treadmill—meaning the rats began to walk voluntarily towards the reward, entirely supporting their own weight with their hind legs.

“This is the world-cup of neurorehabilitation,” exclaims Courtine. “Our rats have become athletes when just weeks before they were completely paralyzed. I am talking about 100% recuperation of voluntary movement.”

In principle, the radical reaction of the rat spinal cord to treatment offers reason to believe that people with spinal cord injury will soon have some options on the horizon. Courtine is optimistic that human, phase-two trials will begin in a year or two at Balgrist University Hospital Spinal Cord Injury Centre in Zurich, Switzerland. Meanwhile, researchers at EPFL are coordinating a nine million Euro project called NeuWalk that aims at designing a fully operative spinal neuroprosthetic system, much like the one used here with rats, for implanting into humans.

Citation:“Restoring voluntary control of locomotion after paralyzing spinal cord injury” Science, June 1st 2012
Authors: Rubia van den Brand, Janine Heutschi, Quentin Barraud, Jack DiGiovanna, Kay Bartholdi, Michèle Huerlimann, Lucia Friedli, Isabel Vollenweider, Eduardo Martin Moraud, Simone Duis, Nadia Dominici, Silvestro Micera, Pavel Musienko, and Grégoire Courtine.

Source: Reuters
Updated May 31, 2012 2:43:30 PM ET

LONDON — Scientists in Switzerland have restored full movement to rats paralyzed by spinal cord injuries in a study that spurs hope that the techniques may hold promise for someday treating people with similar injuries.

Gregoire Courtine and his team at Ecole Polytechnique Federale de Lausanne saw rats with severe paralysis walking and running again after a couple of weeks following a combination of electrical and chemical stimulation of the spinal cord together with robotic support.

"Our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles," said Courtine, whose results from the five-year study will be published in the journal Science on Friday.
Courtine is quick to point out that it remains unclear if a similar technique could help people with spinal cord damage but he adds the technique does hint at new ways of treating paralysis.

Other scientists agree.

"This is ground-breaking research and offers great hope for the future of restoring function to spinal injured patients," said Elizabeth Bradbury, a Medical Research Council senior fellow at King's College London.
But Bradbury notes that very few human spinal cord injuries are the result of a direct cut through the cord, which is what the rats had. Human injuries are most often the result of bruising or compression and it is unclear if the technique could be translated across to this type of injury.

A combination of electrial and chemical stimulation were used to stimulate the spinal cords of rats with spinal cord injuries and severe paralysis for a study that will be published in the journal Science.

It is also unclear if this kind of electro-chemical "kick-start" could help a spinal cord that has been damaged for a long time, with complications like scar tissue, holes and where a large number of nerve cells and fibres have died or degenerated.
Nevertheless, Courtine's work does demonstrate a way of encouraging and increasing the innate ability of the spinal cord to repair itself, a quality known as neuroplasticity.

Other attempts to repair spinal cords have focused on stem cell therapy, although Geron, the world's leading embryonic stem cell company, last year closed its pioneering work in the field.

The brain and spinal cord can adapt and recover from small injuries but until now that ability was far too limited to overcome severe damage. This new study indicates that recovery from severe injury is possible if the dormant spinal column is "woken up".

Norman Saunders, a neuroscientist at the University of Melbourne in Australia, said in an emailed statement reacting to the study that although it remains to be seen whether the technique can be translated to people, "it looks more promising than previously proposed treatments for spinal cord injury".

Bryce Vissel, head of the Neurodegenerative Diseases Research Laboratory at the Garvan Institute of Medical Research in Sydney, said the study "suggests we are on the edge of a truly profound advance in modern medicine: the prospect of repairing the spinal cord after injury".

Courtine hopes to start human trials in a year or two at Balgrist University Hospital Spinal Cord Injury Centre in Zurich.

Source: University of California - San Francisco
Date: January 19, 2012

By Kristen Bole 

UCSF scientists have discovered the unexpected way in which a key cell of the immune system prepares for battle. The finding, they said, offers insight into the processes that take place within these cells and could lead to strategies for treating conditions from spinal cord injury to cancer.

The research focused on the neutrophil, the most common type of white blood cell. Like other cells in the immune system, its job is to seek out and destroy bacteria, viruses or other foreign entities that enter the bloodstream or organs. Scientists have known that, to do this, each cell changes its otherwise amorphous shape to form a single front, or leading edge, that approaches the invader and leads the cell into attack.

The leading edge is thought to send out some type of signal to the rest of the cell to prevent the formation of secondary fronts. Until now, scientists thought the signal was transmitted by the movement of molecules from one part of the cell to another.

Now, however, a team of researchers at the University of California, San Francisco, has shown that the neutrophil triggers this long-range inhibition by transmitting mechanical force.

The process relies on the assembly of a protein known as actin, which accumulates in the part of the cell that pushes out in the direction of its bacterial target.

In their paper, published today in the journal Cell (January 20, 2011), the team showed that the cell’s protrusion stretches its membrane, taking it from lax to tight, like the rope in a game of tug-of-war. The tension is transmitted along the cell membrane, moving from front to back. It is this tension that restricts activity to the leading edge.

“Thiscritical ability of cells to restrict activity to specific regions of their surface is essential for many processes, ranging from the regulation of cell division to the formation of multicellular organisms and the wiring of the nervous system,” said lead author Orion Weiner, PhD, an assistant professor in residence at UCSF’s Cardiovascular Research Institute.

The finding may help researchers identify new therapies that can promote or block the process of cell mobilization as a way of intervening in conditions, he said. After a spinal cord injury, for example, neurons don’t readily cross the site of the injury, impairing motor function or leading to paralysis. There may be drugs that can help the neurons form a leading edge and enable them to jump the gap, Weiner said. Other drugs might impede cells from migrating inappropriately as they do in cancer.

To reach their conclusion, Weiner and his colleagues conducted a series of experiments in which they applied or removed tension from neutrophils and tracked the accumulation of actin and the movement of the cell. Andrew Houk, a graduate student in Weiner’s lab, conducted many of the experiments. They showed that tension is necessary and sufficient to constrain the spread of an existing front and keep a cell from forming a second one.

“Our study establishes tension as a central regulator of this process of leading-edge formation,” Weiner said. “The challenge now is to figure out which molecules respond to that tension and how.”

Source: University of California - San Francisco
Date: January 18, 2012

Dogs with spinal cord injuries may soon benefit from an experimental drug being tested by researchers at the University of California, San Francisco (UCSF) and Texas A&M College of Veterinary Medicine & Biomedical Sciences -- work that they hope will one day help people with similar injuries.

Funded through a three-year, $750,000 grant from the U.S. Department of Defense, the drug to mitigate damage has already proven effective in mice at UCSF. Now the Texas team will test how it works in previously injured short-legged, long torso breeds of dog like dachshunds, beagles and corgis, who often suffer injuries when a disk in their back spontaneously ruptures, damaging the underlying spinal cord.

About 120 dogs a year that develop sudden onset hind limb paralysis after such injuries are brought to the Small Animal Hospital of Texas A&M University, where they receive surgical and medical treatment similar to that for human spinal cord injury. Now, researchers will test whether the new treatment works on some of these dogs, with their owners' consent.

"It would be phenomenal if it works," said Linda J. Noble-Haeusslein, PhD, a professor in the UCSF departments of Neurological Surgery and Physical Therapy and Rehabilitation Science who designed the intervention. "We are in a unique position of being able to treat a dog population where there are simply no current therapies that could effectively improve their hind limb function."

The new treatment does not seek to regrow injured pathways in the spinal cord. Instead, it aims to mitigate damage secondary to the spinal cord injury. Most spinal cord injuries trigger a cascade of chemical reactions in the spinal cord that collectively damage nearby cells and pathways, contributing to functional deficits including hind limb function.

A few years ago, Noble and her UCSF colleague Zena Werb, PhD, showed how blocking the action of one protein found in the spinal cord of mammals can help mice recover from spinal cord injuries. This protein, called matrix metalloproteinase-9, can degrade pathways within the cord and cause local inflammation, leading to cell death.

The injured dogs offer a great opportunity to take the next step on this treatment because their injuries more closely mimic spontaneous human spinal cord injury and, as is the case with humans, no existing treatment has substantially reduced paralysis.

Noble's co-investigator on the new study, Jonathan Levine, DVM, an assistant professor in neurology at Texas A&M University, will treat the dogs through injections of a protein-blocking drug. He will then help the dogs through rehabilitation and assess their recovery. Ongoing studies at UCSF focus on further refining delivery of the drug so as to optimize recovery.

Other researchers have shown that movement can be preserved if as little as 18 percent to 20 percent of the nerve fiber tracts in the spinal cord remain intact.

If successful, the trials in injured dogs may lead to the development of similar treatments for people who suffer spinal cord injuries, Noble said. These are among the most expensive injuries: every person with an injured spinal cord costs the health care system millions of dollars over his or her lifetime.

Such costs often are overshadowed by the tragic and devastating personal price of the injuries, which dramatically alter lives and most often occur in younger people, with long lives in front of them. According to the National Spinal Cord Injury Statistical Center, based at the University of Alabama, Birmingham, most of the 12,000 Americans who suffer spinal cord injuries are between the ages of 16 and 30.

As of this year, some 265,000 people in the United States are living with such injuries, according to the national center. This includes many wounded soldiers who have returned home from war zones.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Help spinal cord injury and stem cell research activist Sabrina Cohen win $50,000 for her foundation, the Sabrina Cohen Foundation for Stem Cell Research (SCF), that funds stem cell and spinal cord injury research  by voting for her in the "America Inspired" Contest!  You can vote once a day, for two weeks! Voting ends on January 27. THANKS!

Source: Stanford University School of Medicine
Date: December 16, 2011

BY KRISTA CONGER

Two months ago, 23-year-old Katie Sharify, a former student at the University of Southern California majoring in international relations and communications, knew very little about human embryonic stem cell research. But now she’s a vocal advocate for the field, which sparks outrage in some circles with its reliance on cells derived from human embryos.

“It doesn’t seem controversial to me,” said Sharify. “If there is something in the medical field that could possibly help people, why wouldn’t you pursue it?”

Many physicians and researchers agree. But Sharify has more than an academic interest in the topic: On Nov. 2, she was in a devastating car accident that left her paralyzed from the waist down. On Nov. 16, she became the fifth person in the country to receive a human embryonic-stem-cell-derived therapy aimed at testing whether the cells are safe to use in humans.

The procedure was performed by Stanford neurosurgeon Gary Steinberg, MD, PhD at the Rehabilitation Trauma Center at the Santa Clara Valley Medical Center. Steinberg is the Bernard and Ronni Lacroute-William Randolph Hearst Professor in Neurosurgery and Neurosciences at Stanford and the principal investigator of the Stanford/SCVMC portion of the nationwide, multicenter trial.

In a strange twist of fate, the trial in which Sharify had enrolled, which was sponsored by Menlo Park-based Geron Corp., was discontinued two days before her treatment.

“It was very unfortunate,” said Sharify. “At that point I felt very let down and didn’t know if I wanted to go forward with the procedure. But then I decided that five patients were still better than four, and that I could still have some sort of an impact.”

The Geron trial was the first to implant cells derived from human embryonic stem cells into human patients. For the spinal cord injury trial, researchers at Geron and UC-Irvine developed a way to coax human embryonic stem cells to become a mixture of cells that include oligodendrocyte precursors. Oligodendrocytes are cells in the brain and the central nervous system that wrap nerve cells with an insulating material called myelin. This myelin sheath is necessary for the transmission of the electric signals along the spinal cord that trigger muscles to move, and relay our sense of touch and temperature. Damage to this sheath caused by trauma is a common cause of paralysis. As a trial participant, Sharify received an injection of about 2 million specialized cells called GRNOPC1 directly to the injured area of her spinal cord.

Doctors don’t expect the cells to help Sharify walk again; phase-1 trials are designed simply to test whether a particular therapy is safe. But her willingness to speak up for human embryonic stem cell research could be important in a field that can be both politically and fiscally tenuous.

“I believe Katie is a very courageous and incredibly optimistic individual,” said Steinberg. “I greatly admire her positive attitude and the way she has responded to her accident by becoming a passionate advocate for developing novel strategies to treat spinal-cord-injured patients, including stem cell therapy. She is an inspiration to all of us.”

Sharify was released from Valley Medical Center on Dec. 14, although she will be returning there from her family’s home in Pleasanton for follow-up visits and rehabilitation sessions.

“I really want to be an advocate,” said Sharify. “Up until this point, I had no passion in my life. I had changed my major in college a few times, but was not very enthusiastic about any of them. For once in my life, I’m very passionate about something. This is something to live for.”

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

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).

"We are extremely pleased with our progress in this innovative trial," said Stephen Huhn MD, FACS, FAAP, Vice President and Head of the CNS Program at StemCells, Inc. "Having completed dosing of the AIS A cohort, screening for AIS B patients, who have a less severe, incomplete type of spinal cord injury, can now begin. Of course, our first priority is to assess safety in each patient, but we will also be evaluating trial patients for changes in sensation, motor and bowel/bladder function." 

"I am also pleased to announce," added Martin McGlynn, President and CEO, "that, in consultation with the clinical team at Balgrist Hospital, the Company has decided to open enrollment for the remainder of the trial to patients living in the United States and Canada. We have received a large number of inquiries from patients in both countries, and hopefully this decision will come as good news to the spinal cord injury community, who were greatly disappointed by Geron's recent decision to discontinue its spinal cord injury trial. We remain optimistic about the prospect of being able to demonstrate safety and clinical utility of our cells in this devastating condition, and are committed to funding our spinal cord injury program until such time as we can come up with a definitive outcome."

About the Clinical Trial

The Phase I/II clinical trial of StemCells, Inc.'s HuCNS-SC purified human adult neural stem cells is designed to assess both safety and preliminary efficacy. Twelve patients with thoracic (chest-level) neurological injuries at the T2-T11 level are planned for enrollment. The first three patients all have injuries classified as AIS A, in which there is no apparent neurological function below the injury level. The second and third cohorts will be patients classified as AIS B and AIS C, those with less severe injury, in which there is some preservation of sensory or motor function. In addition to assessing safety, the trial will assess preliminary efficacy based on defined clinical endpoints, such as changes in sensation, motor and bowel/bladder function. Prior to dosing the next cohort, data from previous cohorts will be reviewed by an independent Data Safety Monitoring Committee.

All patients will receive HuCNS-SC cells through direct transplantation into the spinal cord and will be temporarily immunosuppressed. Patients will be evaluated regularly in the post-transplant period in order to monitor and assess the safety of the HuCNS-SC cells, the surgery and the immunosuppression, as well as to measure any recovery of neurological function below the injury site. The Company intends to follow the effects of this therapy long-term, and a separate four-year observational study will be initiated at the conclusion of this trial.

The trial is being conducted at Balgrist University Hospital, University of Zurich, a world leading medical center for spinal cord injury and rehabilitation. For information on patient enrollment, interested parties may contact the study nurse either by phone at +41 44 386 39 01, or by email at stemcells.pz@balgrist.ch.

Additional information about the Company's spinal cord injury program can be found on the StemCells, Inc. website at http://www.stemcellsinc.com/Therapeutic-Programs/Clinical-Trials.htm and at http://www.stemcellsinc.com/Therapeutic-Programs/Spinal-Cord-Injury.htm, including video interviews with Company executives and independent collaborators.

Here's a news story about a patient in Geron's spinal cord injury trial from the San Jose Mercury News.  Be sure to watch the accompanying video!  Here's a second story from the San Francisco Chronicle about the trial.

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

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.

“These types of systems have to be developed if you ever want to get to a human-on-a-chip that recreates human function,” said James Hickman, a UCF bioengineer who led the breakthrough research. “It’s taken many trials over a number of years to get this to occur using human derived stem cells.”

Hickman’s 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.

Hickman is excited about the future of his research because several federal agencies recently launched an ambitious plan to jump-start research in “human-on-a-chip” models by making available at least $140 million in grant funding.

The National Institutes of Health (NIH), the Defense Advanced Research Projects Agency (DARPA), and the Federal Drug Administration (FDA) are leading the research push.

The goal of the call for action is to produce systems that include various miniature organs connected in realistic ways to simulate human body function. This would make it possible, for instance, to test drugs on human cells well before they could safely and ethically be tested on living humans. The technique could potentially be more effective than testing in mice and other animals currently used to screen promising drug candidates and to develop other medical treatments.

Such conventional animal testing is not only slow and expensive, but often leads to failures that might be overcome with better testing options. The limitations of conventional testing options have dramatically slowed the emergence of new drugs, Hickman said.

The successful UCF technique began with a collaborator, Brown University Professor Emeritus Herman Vandenburgh, who collected muscle stem cells via biopsy from adult volunteers. Stem cells are cells that can, under the right conditions, grow into specific forms. They can be found among normal cells in adults, as well as in developing fetuses.

Nadine Guo, a UCF research professor, conducted a series of experiments and found that numerous conditions had to come together just right to make the muscle and spinal cord cells “happy” enough to join and form working junctions. This meant exploring different concentrations of cells and various timescales, among other parameters, before hitting on the right conditions.
“Right now we rely a lot on animal systems for medical research but this is a pure human system,” Guo said. “This work proved that, biologically, this is workable.”

Besides being a key requirement for any complete human-on-a-chip model, such nerve-muscle junctions might themselves prove important research tools. These junctions play key roles in Amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease, in spinal cord injury, and in other debilitating or life threatening conditions. With further development, the team’s techniques could be used to test new drugs or other treatments for these conditions even before more expansive chip-based models are developed.

Source: Geron Corporation
Date: October 20, 2011

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.

"We are pleased to report that the lowest intended dose of GRNOPC1 has been administered to four patients with complete thoracic spinal cord injuries," said Stephen M. Kelsey, M.D., Geron's Head of Research & Development and Chief Medical Officer. "To date, GRNOPC1 has been well tolerated with no serious adverse events."

Phase 1 Clinical Trial Data

Data were presented on four patients with neurologically complete American Spinal Injury Association (ASIA) Impairment Scale grade A thoracic spinal cord injuries, who received GRNOPC1 at a dose of two million cells delivered by injection into the lesion site using a syringe positioning device designed by Geron. GRNOPC1 was administered between 7 and 14 days after injury. Low-dose tacrolimus was given for temporary immune-suppression from the time of injection for 46 days, at which point the dose was tapered and withdrawn completely at 60 days.

Endpoints of the trial are safety and evaluation of neurological function, using standardized testing at specified timepoints to monitor sensory and lower extremity motor function. The trial protocol also includes multiple MRI scans. Initial follow-up of patients is one year. One patient in the trial has completed the Day 365 follow-up visit. The most recent patient to be enrolled in the clinical trial has completed the Day 30 follow-up. After one year the patients enter a period of long-term follow-up that includes annual in-person visits for the first five years and subsequent yearly check-ups via telephone for an additional nine years.

Safety data to date from the trial has shown:

No surgical complications during or after the procedures.
No adverse events related to the injection procedures or to GRNOPC1.
A few mild adverse events related to tacrolimus.
No evidence of cavitation in the spinal cord at the injury sites on MRI.
No unexpected neurological changes.
No evidence of immune responses to GRNOPC1.
GRNOPC1 was delivered to four spinal cord injured patients at a dose of two million cells without complications from either the cells or the surgical procedure itself, and without any negative effects on the spinal cord or neurological function of the patients to date. The only side-effects observed were due to the immunosuppressive drug tacrolimus, which is administered for the first two months after injection of GRNOPC1. Furthermore, there is no evidence to date of immune rejection of GRNOPC1, an allogeneic cell therapy, including after withdrawal of immunosuppressive drug.

About GRNOPC1

GRNOPC1 contains hESC-derived oligodendrocyte progenitor cells that have demonstrated remyelinating, nerve growth stimulating and angiogenic properties leading to restoration of function in rodent models of acute spinal cord injury. Preclinical studies have shown that administration of GRNOPC1 significantly improved locomotor activity and kinematic scores of rodents with spinal cord injuries when injected seven days after the injury. Histological examination of the injured spinal cords treated with GRNOPC1 showed improved axon survival and extensive remyelination surrounding the rodent axons. For more information about GRNOPC1, visit www.geron.com/GRNOPC1Trial. For further information about the Phase 1 clinical trial, including location of clinical sites, visit www.clinicaltrials.gov/ct2/show/NCT01217008.

Source: Orange County Register
Published: October 24, 2011 Updated: 3:30 p.m.

By PAT BRENNAN / ORANGE COUNTY REGISTER

The world's first test on patients of a treatment for spinal cord injury using human embryonic stem cells is so far proving safe, one year after the first of four patients received injections.

The treatment, developed by researchers at UC Irvine, involves injection of stem cells into the site of a spinal cord injury within seven to 14 days -- known as "acute" injuries, as opposed to longer-term injuries known as "chronic."

None of the patients has experienced any adverse reactions from the treatment, according to Geron Corp., which is conducting the trials, although a few "mild" adverse reactions were reported from a drug used to suppress the patients' immune responses.

"I'm pretty happy that the treatment appears to be safe at this point," said UCI stem-cell researcher Hans Keirstead, who is not involved in the patient trials but developed the treatment with his colleague, Gabriel Nistor.

The treatment has the potential to restore function below the site of a spinal cord injury, perhaps allowing patients with paralyzed limbs to walk again. It has reversed paralysis in laboratory rats.

And the first patient to receive the injections, Timothy Atchison of Alabama, reported feeling in his legs after the treatment. While the identities of the patients involved is kept secret, Atchison came forward to tell his story to the Washington Post.
Keirstead has said Atchison's report was exciting but anecdotal and not scientifically verified; following typical practice, the first stem-cell trial is intended to check the safety of the treatment.

A second trial will determine its effectiveness.

The stem cells are derived from embryos otherwise destined to be discarded by fertility clinics, but such treatments still can generate controversy among those who oppose the use of stem cells.

Embryonic stem cells have the potential to become many different kinds of cells, raising hope that Parkinson's, Alzheimer's and other diseases could one day be treated with them.

In rats, the cells were shown to form new tissue at the site of spinal cord injury, in some cases restoring motor function.
A second clinical trial, also involving a stem-cell treatment developed at UC Irvine, is underway in Switzerland.

In this case, human neural stem cells from aborted fetuses donated by parents are being used to treat "early chronic" spinal cord injuries -- those three to 12 months old.

The treatment, developed by the UCI husband-wife research team of Brian Cummings and Aileen Anderson, also has reversed limb paralysis in laboratory rodents.

The Swiss trial is checking both safety and effectiveness. The first patient was injected in September.

http://www.sciencedaily.com/releases/2011/10/111018121847.htm
ScienceDaily (Oct. 18, 2011) — Regenerative medicine in spinal cord injuries (SCI) is proving to help the human body create new cell and nerve connections that are severed during this type of injury. In a review of current scientific research for stem cell treatment in SCI published this month in the Springer journal Neurotheraputics, Dr. Michael Fehlings and Dr. Reaz Vawda from the Krembil Neuroscience Centre, Toronto Western Hospital in Ontario, Canada, provide evidence that supports researchers moving beyond the lab to conduct human clinical trials for stem cells.

Spinal cord injuries remain one of the most difficult conditions to overcome. Despite the advances made in surgical interventions, drugs and rehabilitation programs, the cascade of damage that ultimately affects the body at the cellular level cannot be reversed.

Stem cell research brings tremendous hope to those who remain paralyzed after such a devastating injury. But according to Dr. Fehlings, patients are not able to realize the potential benefits of stem cell therapy because research is largely stuck in the laboratory.

“With the exception of a few clinical trials, current research is stalled at the animal model stage,” said Dr. Fehlings. “Scientists from around the world have demonstrated as much as they can in lab models that stem cells have an impact on spinal cord injuries and can be transplanted into patients. Now we need the support and coordination of regulatory bodies to move this science forward.

”The study critically evaluates 11 different cell types/sources and the evidence justifying their use. For example, BMSCs (Bone marrow stromal cells ) have an established safety record, as well as a beneficial effect after thoracic SCI. Glial restricted progenitors (GRPs) and oligodendrocytic progenitors (OPCs) are described to have a track record that favours the continuation of more clinical trials and Neural Progenitor Cells (NPC), of which one line of immortalized foetal NPCs has been subjected to extensive pre-clinical safety testing, may have potential benefits.

Spinal cord injuries not only cause life-long disability and carry major psychological effects, injuries to the cervical spine (neck) have a mortality rate of 10 percent in the first year following injury and an expected lifespan of only 10 – 15 years post injury.

Some of the evidence for increasing and expanding clinical trials from the study includes:

There are more than a dozen recently completed, ongoing or recruiting cell therapy clinical trials for SCI.
No experimental mode, rodent or otherwise, will completely mimic the human condition and it is an unrealistic hurdle for all pre-clincial findings to be validated in animals.
There are substantial pre-clinical and earlier clinical safety studies of satisfactory quality and reliability carried out so far to justify the immediate translation into the clinic.
Advances in the application of regenerative neuroscience to SCI can only be made with an investigative approach that balances excellent preclinical research with rigorous ethical clinical trials.
“At this time, a strong patient advocacy base would likely help provide momentum to help translate current research into clinical applications,” said Dr. Fehlings. “Moving forward, all clinical trails must involve peer-reviewed assessment, regulation, independent monitoring, duplication, transparency and accurate record keeping of the every step of the process.”Dr. Fehlings acknowledges that no clinical intervention is 100 percent risk free and uses the examples of other novel therapies such as bone marrow transplantation and the polio vaccine to illustrate how science has forged ahead successfully, despite setbacks along the way.