Cerebral Palsy Stem Cell Treatment, Research, Therapy, Information   

Stem Cell Therapy for Cerebral Palsy

Because cerebral palsy is the result of neurological developmental injury, cerebral palsy patients are prime candidates for stem cell therapy.

Stem cells, especially neuronal progenitor cells, are present in umbilical cord blood. In the brain, neuronal progenitor cells have been shown to differentiate into new tissue circuitry that is needed for a variety of specialized neural functions. Effective neural function, of any type, depends to a great extent on the establishment of precise physical pathways and connections that allow electrical communication between individual neurons and between entire classes of neurons; stem cells derived from umbilical cord blood have been shown to repair these types of connections.

In a new grant from the American Heart Association, combined with an existing grant from the National Institutes of Health, Dr. James E. Carroll, Chief of the Section of Pediatric Neurology at the Medical College of Georgia, is working with an animal model of cerebral palsy in order to identify the best method for transplanting stem cells into the brain, where differentiation into specialized tissue can then occur. Dr. Carroll's work involves the use of chemokines, which are growth factors that are temporarily produced in the brain as part of the normal healing process after an injury. Chemokines attract white blood cells and are summoned to the sites of injury, so scientists hope that by using extra chemokines they might also be able to attract stem cells to the injury site as well, even long after the injury has occurred. Preliminary results indicate that the stem cells are indeed attracted to the sites of injury, but the extra chemokines are needed in order to attract enough of the stem cells to repair the tissue.

Dr. Carroll has 2 methods by which he delivers the stem cells to the sites of injury. In one method, he injects the chemokines into the site of injury first, after which he then injects the stem cells. In the other method, the chemokines have already been transferred inside the stem cells before the stem cells are injected into the injured site, in a manner similar to that by which a virus infects a cell.

Other researchers, working with stem cells in the treatment of other neurological diseases besides cerebral palsy, have already had very promising results. One such case involves a research team at Stanford University who has had success in using stem cells to treat rats with stroke damage. The fact that stem cells have been shown to transform into neurons and support astrocytes in the brain, whether for stroke victims or for people suffering from other types of neurological damage, is encouraging for those researchers who are working to develop treatments of cerebral palsy with stem cells.

Dr. Carroll, who also treats patients with cerebral palsy, cites the work of his colleagues, Drs. David Hess and William D. Hill, who are working with an animal model on the treatment of stroke with mature stem cells derived from bone marrow. In a similar study, Dr. Carroll has used two different stem cell lines in his animal model of cerebral palsy, in order to determine which is most effective: hematopoietic or stromal cells derived from bone marrow. Later, Dr. Carroll is also planning to use oligodendrocyte cells, which manufacture the insulation for brain cells and which appear to be the most damaged in cerebral palsy. Researchers in Japan have already demonstrated that bone marrow stromal cells regenerate brain tissue, and Dr. Carroll hopes that clinical trials may begin within the next few years. The next step will then be to offer the treatment to patients who have cerebral palsy, using the particular cell line that Dr. Carroll will have determined to be the most effective.

There is also great interest among researchers in the brain's ependymal cells, which have been known to separate the fluid that surrounds the brain and spinal cord from neural tissue; now these cells are also believed to contain the brain's greatest reserve of stem cells, which can develop into mature neurons and supporting cells such as glia.

It has further been shown that brain cells (from the ectoderm) can become bone marrow cells (from the mesoderm), and that bone marrow cells in turn can become liver (from the endoderm). The ability of stem cells to migrate throughout the brain has also been widely researched. This homing tendency of stem cells, by which they are naturally attracted to nerves that have been damaged, and by which they transform themselves into specialized nerve cells of the appropriate type, is increasingly being understood in greater detail.

Indeed, because of discoveries such as these, the treatment of cerebral palsy by stem cells is not only a promising new therapy for children, but for adults as well.

One of the most remarkable features of the human brain is its plasticity (its ability to re-grow), even when fully mature. Although evidence to this effect had existed in the past, the first formal report making such an announcement to the scientific community came in October of 1990, when Dr. Fred H. Gage, director of the Laboratory of Genetics at the Salk Institute for Biological Studies outside of San Diego, California, in collaboration with some researchers in Sweden, reported that the adult brain is able to grow new cells in the hippocampus. This revolutionary news disproved the prior dogma that brain cells cannot regenerate after reaching adulthood. Extensive research with mice, conducted in a multitude of laboratories around the world, has since verified that neuronal stem cells do indeed migrate to various parts of the adult brain, where they grow into new neurons. Not only is it now commonly understood that neurogenesis does occur in the adult brain, but it is also now understood that the specific roles of brain tissue may be "reassigned". In an unusually striking example of the brain's ability to re-wire itself, researchers at the Massachusetts Institute of Technology have reconfigured the brains of newborn ferrets so that the animals' eyes are hooked up to the neurological regions in which hearing normally develops. The results of this surprising experiment demonstrated that the ferrets developed fully functional visual pathways in the auditory regions of their brains. In other words, they grew to see the world, visually, with brain tissue that was believed to be exclusively capable only of hearing sounds. Clearly, ongoing discoveries such as these continue to reveal a potential for re-growth, restructuring and reorganization in the brain which was never before fully recognized.

Such findings have significant implications for adult patients, as well as for children, who are suffering from cerebral palsy. If the original neural tissue, which was damaged by the cerebral palsy, cannot be repaired and regrown itself, it is possible that other, collateral, neural tissue may be recruited and "reassigned" to the functions which need to be restored, through stem cell therapy.

Dr. Gerald Fischbach, a previous director of the National Institute of Neurological Disorders and Stroke (part of the National Institutes of Health), has stated that, "Stem cell biology is enormously exciting right now and holds promise for really novel therapies - not just for symptomatic therapies, but perhaps even for cures." (From the website of the National Institute of Neurological Disorders and Stroke).

Dr. Ronald McKay, also of the National Institutes of Health, has spoken about the "self-assembling" tendency of tissue in general, not only neurological tissue, once the cells (and stem cells) are given the right cues. According to Dr. McKay, soon it will be possible that "…people will routinely be reconstituting liver, regenerating heart, routinely building pancreatic islets, and routinely putting cells into brains that get incorporated into the normal circuitry. They will routinely be rebuilding all tissues." (Ibid.)

Dr. Evan Snyder, Professor of Neurology at Harvard Medical School and a researcher in the Department of Neurology at Boston's Children's Hospital, was the first to isolate and grow neural stem cells (NSCs), in the early 1990s. His research has shed much light on the various mechanisms underlying the cellular plasticity of the mammalian nervous system, and the processes by which murine and NSCs make their commitment and differentiation "decisions" during development, degeneration and regeneration. Under Dr. Snyder's direction, the Snyder Laboratory continues to lead this exciting new field of research in the emerging discipline of "restorative neurobiology".

In an ongoing study, the Steenblock Research Institute has been gathering the clinical responses of patients who have undergone umbilical cord stem cell therapy. The research to date shows that micro-environmental changes are occurring in the brains and bodies of many of the patients with cognitive and motor functioning problems, especially in children who have cerebral palsy, but even in adults. Test results show significant improvements in muscle tone, leg movement, hip movement, balance with sitting and standing, vocabulary, thinking and understanding.

Perhaps some of the most dramatic results documented thus far are from Dr. Joanne Kurtzberg's research program at Duke University Medical Center in North Carolina. In fact, she was featured in the August 7th, 2006 issue of Time Magazine, in a cover story entitled, "The Truth About Stem Cells: The Hope, the Hype, and What it Means for You." As this issue of Time Magazine described:

"If you want to lean out over the edges of science and marvel at what is now possible, visit Dr. Joanne Kurtzberg's program at Duke University Medical Center. Children with blood diseases that were almost certainly fatal a decade ago have got cord-blood transplants that essentially cure them. Now she and her team are taking a more targeted approach by attempting to differentiate cord-blood cells to address heart, brain and liver defects. 'I think cord-blood cells have a lot of promise for tissue repair and regeneration,' says Kurtzberg." (From pg. 46).

Indeed, several notable patients have already demonstrated dramatic improvement as a result of Dr. Kurtzberg's use of autologous (i.e., the donor and the recipient are the same person) cord blood stem cells. One case involved a 3-year-old boy who had suffered from cerebral palsy since birth, and who then received his own cord blood stem cells which Dr. Kurtzberg administered to him. Within 8 months of treatment, he was proclaimed free of cerebral palsy.

As his parents discovered, the most difficult aspect of the treatment was simply finding someone who would agree to administer the stem cell therapy. Despite initial resistance from researchers who refused to perform the "experimental" procedure, the parents persisted and eventually found Dr. Kurtzberg at the Duke University Medical Center. She agreed to perform the 20-minute-long procedure, after which the boy was carefully monitored. His feeding difficulties and apraxia (the inability to execute voluntary motor movement) disappeared within 30 days of the treatment, and after 8 months he no longer needed physical therapy, his spasticity was replaced by normal dexterity, and for the first time in his life he was finally categorized at the normal weight, height and developmental stage for his age. Also for the first time in his life, he began speaking in full sentences.

The boy's mother met with President George W. Bush in July of 2006 to discuss the results of this treatment, and she is currently actively focused on educating others about the benefits of cord blood stem cells. Articles related to her son's cure will be posted soon at the website of the Evanosky Foundation.

A detailed description of her son's treatment may also be read at www.stemcellresearch.org.

Another case involved a 6-month-old female infant suffering from anoxic brain injury, due to a lack of oxygen at birth. At 2 months of age, the child was diagnosed with "moderate to severe" brain damage in 3 of the 4 lobes of her brain, by doctors at Children's Hospital in Washington, D.C.. Since the parents had banked the child's cord blood at birth with the Cord Blood Registry (CBR), the hard part, once again, was simply finding a doctor who was willing to administer the cord blood stem cells to the child. Since most places - including doctors at the National Institutes of Health (NIH) and the Mayo Clinic - declined to conduct the new procedure, the parents contacted Dr. Joanne Kurtzberg at Duke University, who, once again, agreed to perform the stem cell transfusion. The parents then brought their infant daughter, then 5 months old, to Dr. Kurtzberg while the CBR immediately transferred the child's cord blood stem cells to Duke University. After receiving her own stem cells, the child showed noticeable improvement within 2 weeks.

Dr. Joanne Kurtzberg and her colleague, Dr. Donald Beam, have successfully harvested, isolated and grown oligodendrocytes from umbilical cord blood; this particular type of stem cell has been shown to reverse demyelination and repair the damage that has been caused by this absence of myelin. While cerebral palsy, technically speaking, is not a demyelinating disease per se, but rather is a disease that involves delayed and aborted myelination, the role of oligodendrocytes in re-myelinating the affected axons is nevertheless crucial in the treatment of cerebral palsy. According to the website of The Myelin Project, myelin is defined as:

"…the white matter coating our nerves, enabling them to conduct impulses between the brain and other parts of the body. It consists of a layer of proteins packed between two layers of lipids. Myelin is produced by specialized cells: oligodendrocytes in the central nervous system, and Schwann cells in the peripheral nervous system. Myelin sheaths wrap themselves around axons, the threadlike extensions of neurons that make up nerve fibers. Each oligodendrocyte can myelinate several axons."

The Myelin Project describes itself as "an international grassroots organization whose mission is to accelerate medical research on myelin repair." (From www.myelin.org). The scope of its activities impacts a multitude of diseases. Many neurodegnerative disorders, such as the various leukodystrophies, as well as acquired diseases such as multiple sclerosis, are all demyelinating diseases. Although cerebral palsy falls under a separate category, it can, nevertheless, be treated by the same repair of demyelinated nerves, with these same oligodendrocyte cells that are specialized for the regrowth and repair of myelin. Similarly, the various leukodystrophies also involve a disorder of the white matter of the brain, which is the part of the brain that contains the myelinated nerve fibers, and it is known as "white matter" because it is white, which is the color of myelin. By contrast, the gray matter of the brain, such as the cortex, which contains the nerve cell bodies themselves, lacks myelin and therefore visually appears as the color gray instead of white. Dr. Kurtzberg's success in treating cerebral palsy patients has vast implications in the treatment of patients with many of these other, standard demyelinating diseases, such as the various leukodystrophies.

Dr. Kurtzberg expects to begin human trials with oligodendrocyte stem cells in early 2007, with approximately 6 children. If successful, the study will then be expanded to include additional children. The Evanosky Foundation is involved in raising $100,000 in 2006 to support Dr. Kurtzberg's stem cell research at Duke University.

Accounts of other children who have been cured with their own cord blood stem cells are available at the website of the Cord Blood Registry.

On December 20th of 2005, President George W. Bush signed into law a bill establishing a national umbilical cord blood program in which federal funding is provided for the collection and storage of cord blood for life-saving blood cell transplants such as these described above. Since cord blood stem cells are highly preferable to embryonic stem cells, for a number of reasons (please see the sections of this website entitled "Types of Stem Cells", "Embryonic Stem Cells", "Advantages and Disadvantages: A Comparison"), ongoing research in the realm of cord blood stem cells holds great promise.

There is no cost for donating cord blood, and anyone who may be expecting a child is encouraged to make such arrangements. The decision to bank or to donate cord blood should be made by the 34th week of pregnancy, however, in order to allow enough notice to the cord blood banks through one's doctor.

In the U.S., momentum is gathering for the introduction of stem cell therapy in the treatment of cerebral palsy, not only for children, but for adults as well. Parents nationwide, who are already aware of research in this field now have great hope for a higher quality of lives for their children. Additionally, real hope for adults who are suffering with cerebral palsy is now also found in the extensive research that is being conducted by a long list of other scientists on adult brain plasticity and "restorative neurobiology". As a treatment for cerebral palsy, stem cell therapy offers a safe and effective option where previously no such options have existed.

Cerebral Palsy Overview

Rather than being one single, distinct condition, cerebral palsy actually constitutes a group of disorders. Formerly known today as "spastic diplegia", it was originally known as "Little's Disease", after its discoverer, Dr. William Little, the English surgeon who first documented the symptoms in the 1860s.

The United Cerebral Palsy Foundation estimates that 800,000 children and adults in the United States are living with cerebral palsy, and the Centers for Disease Control and Prevention estimate approximately 10,000 new cases each year in the U.S. alone. (From the websites of United Cerebral Palsy (UCP) and the Centers for Disease Control (CDC), respectively).

Although the causes of cerebral palsy generally occur before birth or shortly thereafter, the symptoms usually manifest themselves during the first 3 years of life. Such symptoms typically include a spastic stiffening of muscles primarily in the legs and, to a lesser extent, in the arms. Unlike with most neurological conditions, the symptoms of cerebral palsy do not progressively worsen throughout life, but instead remain relatively constant.

Some individuals may have difficulty with fine motors skills such as writing and cutting, while others might have difficulty maintaining balance and walking. Involuntary movements such as uncontrollable hand motion and drooling may also occur. Symptoms differ from person to person, and even for the same person the symptoms can change over time. Severe cases can cause profound handicaps such as an inability to walk, and the individual may require extensive, lifelong care. However, cerebral palsy does not always completely debilitate. Mild cases may only cause slight awkwardness and the individual may not require special assistance.

Other symptoms associated with cerebral palsy may include mental impairment, seizures or epilepsy, growth problems, impaired vision or hearing, and abnormal sensation or perception.

The early symptoms of cerebral palsy are usually first noticed by the parents, who observe that their child's motor skills are not developing properly. An abnormally slow rate of development in learning to roll over, crawl, smile, sit, stand or walk, for example, might be cause for further examination. Unusual posture and a tendency to favor one side of the body over the other should also not be ignored. Diagnosis is then confirmed through a series of extensive tests. Measuring the child's motor skills and reflexes, looking over the child's medical history, ruling out other disorders with similar symptoms, and conducting evaluations of intelligence, hearing and vision are all part of the assessment process. Specialized tests such as CT (computed tomography), MRI (magnetic resonance imaging), and ultrasonography can expose specific problems in brain tissues, thus clarifying precisely whether or not an individual has cerebral palsy.

The exact causes of cerebral palsy are unknown. Originally, oxygen deficiency (asphyxia) and other complications from premature or difficult births were suspected as causative factors, but this theory was later disproven for all but the rarest of cases. (Please see the 4 types of brain damage, listed below). In a study conducted by the National Institute of Neurological Disorders and Stroke (NINDS, part of the National Institutes of Health) in 1980, in which data from 35,000 newborns and their mothers were analyzed, complications during childbirth were found to account for less than 10% of all cerebral palsy cases. More recent research indicates that viral infections may be involved, although further investigation into this hypothesis is still needed. While a single cause of cerebral palsy has thus never been identified, advances in imaging technology have helped to describe in increasing detail the precise neurological nature of cerebral palsy.

Most of what is known today about cerebral palsy is the result of research that has been conducted within the past two decades. In particular, MRI (magnetic resonance imaging) studies have shed new light on brain morphology (cellular structure) and on other neuro-anatomical characteristics associated with cerebral palsy. Even in the brains of infants and young children who have cerebral palsy, distinct areas of damage and structural malformation have been clearly identified. Some genetic studies have also found certain chromosomal mutations in some cases of cerebral palsy. While the exact causes of the various types of cerebral palsy are therefore not yet known, we do have a very detailed understanding of the distinct neurophysiological characteristics that are unique to cerebral palsy. As our understanding of this unique neurophysiology improves, so does our ability to treat the disease.

Much of the research conducted on cerebral palsy has been funded by NINDS (the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health). According to their website, children with cerebral palsy may exhibit any of the following symptoms, either singly or in combination:

From: NINDS - National Institute of Neurological Disorders and Stroke.

Cerebral palsy is known to originate during specific stages of neurological development. During these developmental stages, four distinct types of brain damage have been identified. These are:

1. Damage to the white matter of the brain (periventricular leukomalacia, or PVL), which usually occurs between 26 and 34 weeks of gestation. During this period of "selective vulnerability", the periventricular white matter is especially sensitive and may suffer permanent damage from fetal or maternal infection. In PVL, the resultant damage looks like tiny holes in the white matter, which interrupt the normal transmission of electrical signals in the brain.
   
   
2. Abnormal development of the brain (cerebral dysgenesis). During the first 20 weeks of fetal development, the growing brain is particularly vulnerable, and infections, fever or trauma that occur during this time period can cause malformations and malfunction in neurological development. Genetic mutations have also been discovered which impair normal development of the brain at this stage. Any assaults upon the developing nervous system during this critical stage of fetal development can potentially have lasting effects.
   
   
3. Bleeding in the brain (intracranial hemorrhage). This type of cerebral bleeding is often the result of fetal stroke, which can occur either from blocked or broken blood vessels, such as from blood clots in the placenta that impede blood flow, or from other abnormalities of blood clotting or weak blood vessels. Maternal high blood pressure (hypertension) during pregnancy, and maternal infection such as pelvic inflammatory disease, have been shown to contribute to the risk of fetal stroke.
   
   
4. A prolonged lack of oxygen to the brain (hypoxic-ischemic encephalopathy, or intrapartum asphyxia). While a certain amount of asphyxia, or lack of oxygen to the brain, is not uncommon in newborns due to the stress of labor and delivery, prolonged asphyxia (lasting more than 10 minutes) can lead to a destruction of brain tissue, including that in the motor cortex. This type of cerebral damage can also be caused by severely low maternal blood pressure, rupture of the uterus, detachment of the placenta, or problems involving the umbilical cord.

Any of these types of developmental problems can lead to the array of symptoms characterized as cerebral palsy. After the symptoms are manifest, the types of symptoms themselves are also divided into 4 categories, which are:

1. Spastic: this is the most common type, in which muscles are permanently contracted.
   
   
2. Athetoid or Dyskinetic: characterized by uncontrolled, writhing, slow movements, usually in the limbs although sometimes also in the face and tongue muscles.
   
   
3. Ataxic: depth perception, balance and coordination are affected, and can be accompanied by tremors.
   
   
4. Mixed: any combination of the aforementioned classifications may occur, with spastic and athetoid being the most common combination.