Researchers at the Doorstep of Stem Cell Therapies for MS, Other Myelin Disorders

Source: University of Rochester Medical Center

Date: October 25, 2012

Summary:

When the era of regenerative medicine dawned more than three decades ago, the potential to replenish populations of cells destroyed by disease was seen by many as the next medical revolution. However, what followed turned out not to be a sprint to the clinic, but rather a long tedious slog carried out in labs across the globe required to master the complexity of stem cells and then pair their capabilities and attributes with specific diseases.

In a review article appearing today in the journal Science, University of Rochester Medical Center scientists Steve Goldman, M.D., Ph.D., ≈, and Martha Windrem, Ph.D., contend that researchers are now on the threshold of human application of stem cell therapies for a class of neurological diseases known as myelin disorders – a long list of diseases that include conditions such as multiple sclerosis, white matter stroke, cerebral palsy, certain dementias, and rare but fatal childhood disorders called pediatric leukodystrophies.

New Approach to Reverse Multiple Sclerosis in Mice Models

Source: Mayo Clinic
Date: June 27, 2012

Summary:

Mayo Clinic researchers have successfully used smaller, folded DNA molecules to stimulate regeneration and repair of nerve coatings in mice that mimic multiple sclerosis (MS). They say the finding, published June 28 in the journal PLoS ONE, suggests new possible therapies for MS patients.

Growth Factor in Stem Cells May Spur Recovery From MS

Source: Case Western Reserve University
Date: May 20, 2012

Summary:

CLEVELAND - A substance in human mesenchymal stem cells that promotes growth appears to spur restoration of nerves and their function in rodent models of multiple sclerosis (MS), researchers at Case Western Reserve University School of Medicine have found. Their study is embargoed until published in the online version of Nature Neuroscience at 1 p.m. U.S. Eastern Standard Time on Sunday, May 20. In animals injected with hepatocyte growth factor, inflammation declined and neural cells grew. Perhaps most important, the myelin sheath, which protects nerves and their ability to gather and send information, regrew, covering lesions caused by the disease. The research is published in the current issue of Nature Neuroscience.

In this study, the researchers first wanted to test whether the presence of stem cells or something cells produce promotes recovery. They injected mice with the medium in which mesenchymal stem cells, culled from bone marrow, grew. All 11 animals, which have a version of MS, showed a rapid reduction in functional deficits.

Researchers Develop Gene Therapy to Boost Brain Repair for Demyelinating Diseases

Source: California Institute of Technology
Date: February 8, 2012

Summary:

Our bodies are full of tiny superheroes—antibodies that fight foreign invaders, cells that regenerate, and structures that ensure our systems run smoothly. One such structure is myelin—a material that forms a protective, insulating cape around the axons of our nerve cells so that they can send signals quickly and efficiently. But myelin, and the specialized cells called oligodendrocytes that make it, become damaged in demyelinating diseases like multiple sclerosis (MS), leaving neurons without their myelin sheaths. As a consequence, the affected neurons can no longer communicate correctly and are prone to damage. Researchers from the California Institute of Technology (Caltech) now believe they have found a way to help the brain replace damaged oligodendrocytes and myelin. The therapy, which has been successful in promoting remyelination in a mouse model of MS, is outlined in a paper published February 8 in The Journal of Neuroscience.

The therapy uses leukemia inhibitory factor (LIF), a naturally occurring protein that was known to promote the self-renewal of neural stem cells and to reduce immune-cell attacks to myelin in other MS mouse models. According to the researchers, LIF enables remyelination by stimulating oligodendrocyte progenitor cells to proliferate and make new oligodendrocytes.

Mice stem cells guided into myelinating cells by the trillions

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

Summary:

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

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

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

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

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

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

Summary:

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

Stem Cells May Show Promise for People with Rapidly Progressing MS

Source: American Academy of Neurology
Date: March 21, 2011

Summary:

ST. PAUL, Minn. – A long term study reports about the effectiveness of replacing bone marrow, purposely destroyed by chemotherapy, with autologous (self) stem cell rescue for people with aggressive forms of multiple sclerosis (MS). The study is published in the March 22, 2011, print issue of Neurology®, the medical journal of the American Academy of Neurology. For the treatment, chemotherapy drugs are used to kill all of the patient's blood cells, including the immune cells that are believed to be attacking the body's own central nervous system. Bone marrow stem cells removed from the patient are purified and transplanted back into the body, which saves life by replacing the blood cells and also is proposed to 'reboot' the immune system.

HealthDay News and WebMD published news stories based on this news release today.

Study reveals new possibility of reversing damage caused by MS

Source: University of Cambridge
Date: 6 December 2010

Summary:

Damage caused by multiple sclerosis could be reversed by activating stem cells that can repair injury in the central nervous system, a study has shown. Researchers from the Universities of Cambridge and Edinburgh have identified a mechanism essential for regenerating insulating layers - known as myelin sheaths - that protect nerve fibres in the brain. In additional studies in rodents, they showed how this mechanism can be exploited to make the brain's own stem cells better able to regenerate new myelin. The study, funded by the MS Society in the UK and the National Multiple Sclerosis Society in America, is published in Nature Neuroscience.

Immune system helps transplanted stem cells navigate in central nervous system

Source: University of California - Irvine
Date: June 1, 2010

Summary:

— Irvine, Calif., — By discovering how adult neural stem cells navigate to injury sites in the central nervous system, UC Irvine researchers have helped solve a puzzle in the creation of stem cell-based treatments: How do these cells know where to go?
Tom Lane and Kevin Carbajal of the Sue & Bill Gross Stem Cell Research Center found the answer with the body’s immune system.
Their study not only identifies an important targeting mechanism in transplanted stem cells but also provides a blueprint for engineering stem cell-based therapies for multiple sclerosis and other chronic neurological diseases in which inflammation occurs. Results appear in this week’s early online edition of the Proceedings of the National Academy of Sciences.

Bone marrow stem cells in MS show promise

Source: University of Bristol
Date: 5 May 2010

Summary:

A groundbreaking trial to test bone marrow stem cell therapy with a small group of patients with multiple sclerosis (MS) has been shown to have possible benefits for the treatment of the disease. Bone marrow stem cells have been shown in several experimental studies to have beneficial effects in disease models of MS. The research team, led by Neil Scolding, Burden Professor of Clinical Neurosciences for the University of Bristol and North Bristol NHS Trust, have now completed a small trial in patients with MS to begin translating these findings from the laboratory to the clinic.

The Bristol team report on this pioneering trial in an article published online in Clinical Pharmacology and Therapeutics. The paper, Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis was performed at the Institute of Clinical Neurosciences, Frenchay Hospital, Bristol and the Bristol Haematology and Oncology Centre.

First stem cell clinical trial for treating brain’s “communication highway” to begin

Source: University of California - San Francisco
Date: September 10, 2009

Summary:

UCSF researchers are set to begin a Phase I clinical trial in collaboration with StemCells, Inc. to test the safety and preliminary effectiveness of using neural stem cells to treat children with a rare, fatal form of a brain disorder known as Pelizaeus-Merzbacher disease (PMD). Currently, there are no effective treatments for the fatal forms of the disease, which affects males that inherit a single defective gene.

The trial is the first neural stem cell trial in the United States designed to treat a disease resulting from a lack of “myelin,” a substance that insulates nerve cells’ communications fibers. Nerve cells communicate through axons that function much like electrical wires. Myelin is the insulating coat that surrounds the axons to prevent short circuits. Damage to the cells in the brain that make myelin, called “oligodendrocytes,” is the hallmark of multiple sclerosis and is involved in certain forms of cerebral palsy.

CBS News Feature story on MS Adult Stem Cell Trial

CBS News reports on the recent trial at Northwestern University using adult stem cells to treat multiple sclerosis in a feature entitled "Treating MS Symptoms With Stem Cells." For previous news coverage of this trial see the SUNDAY, FEBRUARY 01, 2009 entry "Coverage of Northwestern University Multiple Sclerosis Adult Stem Cell Study" below.

Coverage of Northwestern University Multiple Sclerosis Adult Stem Cell Study

Below is a summary of media coverage from various sources of recent studies by researchers at Northwestern University in which adult stem cells reversed symptoms of multiple sclerosis in mice:

Bloomberg News, January 31, 2009: "Dose of stem cells reverses some MS":

"A dose of their own stem cells "reset" the malfunctioning immune system of patients with early-stage multiple sclerosis and, for the first time, reversed their disability, according to researchers at Northwestern University in Chicago. All 21 patients in the study had the "relapsing-remitting" form of the disease that makes their symptoms alternately flare up and recede. Three years after being treated, on average, 17 of the patients had improved on tests of their symptoms, 16 had experienced no relapse, and none had deteriorated, the study found."

Nature, 30 January 2009: "MS stem-cell trial shows promise: Multiple sclerosis treatment seems to reverse symptoms.":

"A stem-cell therapy appears to help some patients with early-stage multiple sclerosis recover, according to results from a preliminary study. In the new trial, the patients' immune cells were first destroyed and they were then injected with blood stem cells taken from their bone marrow. Seventeen of the 21 patients treated in his study improved, suffering fewer problems with their balance or vision, and none declined over the 2-4 years they took part in the study. This marks the first time a technique "has actually shown reversal" of neurologic loss caused by this disease, says Richard Burt of Northwestern University in Chicago, who led the study."

BBC News, 02:21 GMT, Friday, 30 January 2009: "MS stem-cell treatment 'success'":

"Stem-cell transplants may control and even reverse multiple sclerosis symptoms if done early enough, a small study has suggested. ...Stem cells were harvested from the patients and frozen while drugs were given to remove the immune cells or lymphocytes causing the damage. The stem cells were then transplanted back to replenish the immune system - effectively resetting it. Five patients in the study relapsed, but went into remission after receiving other therapy."

The Scotsman, 30 January 2009: "New stem cell treatment can reverse crippling MS":

"A NEW treatment for multiple sclerosis using stem cells could be used to reverse the effects of the disease, research revealed yesterday. A study of 21 patients with MS found that none saw their condition deteriorate while using the therapy – and the majority saw an improvement. The discovery gives new hope that stem cells offer a ground-breaking new method of tackling the debilitating disease, for which there was no cure. The latest research, published in The Lancet Neurology, focused on a technique known as "autologous non-myeloablative haemopoietic stem cell transplantation."

"Stem cells are taken from the patient's bone marrow. The patient's immune system is suppressed and their haemopoietic stem cells – which become blood cells – are put back. Such a technique effectively "resets" the immune system. The 11 women and ten men taking part in the new study, led by the Northwestern University Feinberg School of Medicine in Chicago, suffered from a form of the condition known as relapsing-remitting MS."

New Scientist, 30 January 2009 11:57: "Multiple sclerosis 'reversed' with stem cell therapy":

"For the first time, some of the disability associated with the early stages of multiple sclerosis appears to have been reversed. The treatment works by resetting patients' immune systems using their own stem cells. While randomised clinical trials are still needed to confirm the findings, they offer new hope to people in the early stages of the disease who don't respond to drug treatment."

Daily Mail, 30th January 2009, 11:56 AM: "Stem cell injection offers fresh hope for MS sufferers":

"Stem cell injections can reverse the crippling effects of multiple sclerosis, a study published today says. Four out of five adults in the early stages of MS who were injected with stem cells taken from their bone marrow saw an improvement in symptoms after three years. The rest of the patients saw their condition stabilise."

United Press International, January 29, 2009 at 6:30 PM ET: "Stem cell transplant reverses early MS"

"U.S. medical scientists say they have used stem cell therapy to apparently reverse the neurological dysfunctions caused by early-stage multiple sclerosis. Researchers from Northwestern University's Feinberg School of Medicine said they transplanted early-stage multiple sclerosis patients' own immune stem cells into the patients' bodies, thereby "resetting" their immune systems."

Reuters, January 29, 2009 7:11pm EST: "Stem cell transplants show promise for MS: study":

"U.S. researchers have reversed multiple sclerosis symptoms in early stage patients by using bone marrow stem cell transplants to reset the immune system, they said... Some 81 percent of patients in the early phase study showed signs of improvement with the treatment, which used chemotherapy to destroy the immune system, and injections of the patient's bone marrow cells taken beforehand to rebuild it."

HealthDay News, January 29, 2009: "Stem Cell Transplants Help MS Victims: 'Resetting' overactive immune system in early stages of disease worked, study finds":

"Stem cell transplantation seems to stop and, in some cases, undo neurological damage in people with multiple sclerosis, a small study shows. The trial involved just 21 patients, but a larger, randomized trial is under way in the United States, Canada and Brazil. ...The technique used in this study, autologous non-myeloablative hemopoietic stem cell transplantation, 'resets' the immune system and is already used for secondary-progressive MS."

Stem Cell Transplant Reverses Early-Stage Multiple Sclerosis

Source: Northwestern University:
Date: January 30, 2009

Summary:

Researchers from Northwestern University's Feinberg School of Medicine appear to have reversed the neurological dysfunction of early-stage multiple sclerosis patients by transplanting their own immune stem cells into their bodies and thereby "resetting" their immune systems. The patients in the small phase I/II trial continued to improve for up to 24 months after the transplantation procedure and then stabilized. They experienced improvements in areas in which they had been affected by multiple sclerosis including walking, ataxia, limb strength, vision and incontinence. The study will be published online January 30 and in the March issue of The Lancet Neurology.

Intraspinal implant of mesenchymal stem cells may not heal the demyelinated spinal cord

Source: Source: Cell Transplantation Center of Excellence for Aging and Brain Repair
Date: November 12, 2008

Summary:

Multiple sclerosis is a disease caused by the loss of the myelinated sheath surrounding the nerve fibers of the spinal cord. Therapeutic hope for curing multiple sclerosis and other demyelinating diseases has included the possibility that stem cell transplants could help remyelinate the spinal cord. Accordingly, researchers from the University of Cambridge (UK) conducted experiments using animal models to see if the direct implantation of multipotent mesenchymal stem cells (MSCs) (derived from a different rat's adult bone marrow, i.e. allogenic) into the demyelinated rat spinal cord would be therapeutic and remyelinate the damaged area.

Hadassah Hospital Study Shows That Neural Cells Derived From Human Embryonic Stem Cells Reduce Multiple Sclerosis (MS) Symptoms

Source: Hadasit
Date: September 8, 2008

Summary:

Hadassah University Hospital and Hadasit, the technology transfer company of Hadassah Medical Organization, announced today that scientists at Hadassah University Hospital have discovered a new application for human embryonic stem cells. They have demonstrated for the first time that transplanted neural cells derived from human embryonic stem cells can reduce the clinical symptoms in animals with a form of multiple sclerosis.

Pluristem's PLX-MS Shows Potential Benefit in the Prevention of Multiple Sclerosis

Source: Pluristem Therapeutics Inc.
Posted: August 11, 2008 7:00 am ET

Summary:

Pluristem Therapeutics Inc., a bio-therapeutics company dedicated to the commercialization of non-personalized (allogeneic) cell therapy products for a variety of degenerative, ischemic and autoimmune indications, today announced that the Company’s PLacental eXpanded (PLX-MS) cells have demonstrated in vivo efficacy in the prevention of Multiple Sclerosis (MS). PLX cells are Pluristem’s placental-derived mesenchymal stromal cells (MSCs) that have been expanded in the Company’s proprietary PluriX™ 3-D bioreactor.

Human Stem Cell Transplant Helps Brain-Impaired Mice

Source: HealthDay News
Date: June 4, 2008

Summary:

HealthDay News reports human neural stem cell transplants improved functioning in mice with multiple sclerosis:

"Mice with a congenital brain disorder improved after receiving human neural stem cell transplants, a U.S. study finds. The mice lacked myelin, a substance that plays a critical role in the transmission of electrical signals between nerve cells. When myelin is missing or damaged, electrical signals aren't properly transmitted. These "shiverer" mice typically die within months of birth."

The study compared previous research using cell transplants to restore destroyed myelin with results found in the current study:

"Previous research has examined the use of cell transplantation for restoring absent or lost myelin to diseased nerve fibers. But, until now, no transplantation of human neural stem cells or of their derivatives (glial progenitor cells) had been successful in test animals. In this new study, researchers from the University of Rochester Medical Center and a number of other universities (Cornell, UCLA and Baylor) created a new method for harvesting and purification of human fetal glial progenitor cells. They also developed a new cell delivery strategy that uses multiple injection sites to encourage widespread and dense take-up of the transplanted cells through the central nervous system. When the researchers used these new approaches, the transplanted cells took hold throughout the brain and spinal cord, and the mice showed robust, efficient and functional myelination. Some of the mice showed neurological improvement and a fraction of them were save by the procedure."

Bone marrow treatments restore nerves, expert says

Source: Reuters
Posted: May 6, 2008 2:37pm EDT

Summary:

Reuters reports patients with Multiple Sclerosis experienced remission of their symptoms after receiving bone marrow transplants:

"An experiment that went wrong may provide a new way to treat multiple sclerosis, a Canadian researcher said... Patients who got bone marrow stem-cell transplants -- similar to those given to leukemia patients -- have enjoyed a mysterious remission of their disease. Researchers had thought that destroying the bone marrow would improve symptoms within a year. After all, MS is believed to be an autoimmune disease, in which immune system cells mistakenly attack the fatty myelin sheath that protects nerve strands. Patients lose the ability to move as the thin strands that connect one nerve cell to another wither. Instead, improvements began two years after treatment."

New research reveals critical knowledge about the nervous system

Source: Rutgers University
Date: November 5, 2007

Summary:

Uncover the neural communication links involved in myelination, the process of protecting a nerve’s axon, and it may become possible to reverse the breakdown of the nervous system’s electrical transmissions in such disorders as multiple sclerosis, spinal cord injuries, diabetes and cancers of the nervous system.