Can Stem Cells treat Cerebral Palsy?

In short, yes. More importantly, it can be done safely. At Beike Biotechnology, mesenchymal stem cells are acquired from donated umbilical cord tissue and blood shortly after a baby’s birth, and are subjected to strict and thorough safety protocols.

These stem cells are very safe because they have the ability to treat anyone (there is no HLA matching necessary), they can be administered multiple times over the course of several days, and as non-invasively as a simple IV injection. This is very different in comparison to embryonic stem cells, which have the potential to develop into cancerous tumors. 

What is cerebral palsy? 

Cerebral palsy is an umbrella term for many possible symptoms that arise as a result of damage to a developing brain in the cerebral hemispheres, which controls movement, speech, learning, and more. This brain injury is acquired before, during, or shortly after birth and considered non-progressive. The symptoms can include but are not limited to muscle weakness, general motor control problems, eating, swallowing, coordination, and even problems with cognitive function. There are many possible causes that can be in any combination to cause the symptoms experienced by one person. It is important to understand that because this is largely an umbrella term, no two cerebral palsy patients suffer in exactly the same way. 

What causes cerebral palsy? 

There are a number of causes that could result in the symptoms of CP. Some of the possible causes and contributing factors that often afflict people include: 

• the brain developing in an unusual way, 
• the genes themselves experiencing change that impacts the brain’s cells development,
• infections that happen during pregnancy, 
• physical injury causing brain damage that takes place before, during, or after birth
• Complications in premature birth
• Critical illness at birth (subnormal consciousness, seizure, etc) 
• A shortage or total lack of oxygen to the brain during or shortly after birth (hypoxia/anoxia)
• Neonatal Jaundice and Kernicterus

How does CP manifest itself?

There are many different cells in the brain that are involved in neurological function, allowing the brain and the rest of the body to communicate properly. There are neurons, astrocytes, microglia, oligodendrocytes, ependymal cells, and many more that are needed to make these connections. The way cerebral palsy exhibits itself can be a result of any or all of these cells being damaged, and can depend on which area of the brain is injured. Cerebral palsy can affect the whole body, including speech, motor and cognitive function, just the legs (paraplegia/paraparesis), or one side of the body (hemiplegia/hemiparesis), but this is not an exhaustive list. The physical effects can be categorized in four main forms, seen below: 

Beyond these areas of the body CP can affect, it also can be categorized in the way it affects those areas. This categorization comes in three main forms:

1. Spastic: this is the most commonly seen form, in which muscle tone is increased, causing muscles to feel stiff and movements to look jerky.
2. Dyskinetic: this form causes involuntary movements that can be twisting, repetitive, slow, or unpredictable. This affects 10-15% of cases and can be very severe.
3. Ataxic: this form is characterized by shaky movements that can cause problems with balance, coordination, spatial positioning, posture, and even the control of eye movements. 5% of cerebral palsy patients have this.
4. Any mixture of these three forms is possible as well. 

Diagnosis is generally determined after doctors look at an MRI of the patient’s brain coupled with observed symptoms. The patient is also tracked throughout childhood to monitor the pace of important developmental milestones such as crawling and walking.

How is cerebral palsy treated?

As of now, there is no cure for cerebral palsy. Therapies that treat cerebral palsy are for the purpose of helping to mitigate and make symptoms more manageable, especially in terms of making communication less difficult. There are a number of different areas within the disease that can be helped, and often a cerebral palsy patient will work with many types of doctors to improve on many fronts. Medications exist for patients that have need to relax stiff muscles, and to address some feeding problems in babies. Physical therapy and occupational therapy can help improve a patient’s mobility or ability to perform daily tasks, and speech therapy can be used to improve communication skills. For the most part, therapy and medications are viewed as positive interventions to manage the condition, but as in all areas of medicine, some uncertainty and disagreement exists about what and when is best. One of the more new and promising treatments, however, is treatment with stem cells.

What are stem cells?

Our human body is made up of about 200 different types of cells, such as skin, blood, and muscle cells. These specialized cells have unique jobs and responsibilities within our body, but they are unable to generate new identical cells when required. The job of stem cells, however, is to provide new specialized cells when old ones die, are damaged, or lost, which allows for regeneration, healing, and growth. Stem cells are able to do this as they are not only able to self replicate but also turn into any cell needed in their designated area of the body (defined below). With such great potential, scientists hope to use stem cells transplanted into the body to help replace or repair damaged tissues and nerves. 

However, there are different types of stem cells, and they are defined by both their ability to develop and their origin, but these two characteristics are intertwined. The most powerful type of cell is the fertilized egg, and it is described as totipotent, because it develops from one cell into all other cells, ultimately creating a human being. The next most powerful cells are pluripotent stem cells, because they can divide into every kind of human tissue, but cannot create an entire organism the way the fertilized egg can. Following the pluripotent stem cells are the multipotent stem cells, which can divide and create a specific range of cell types. Oligopotent stem cells, similar to multipotent cells, are able to differentiate into a limited range of similar cell types. Lastly, there are unipotent stem cells which, as their name suggests, are only able to differentiate into one type of cell.

Embryonic vs Adult Stem Cells 

Defined by origin, stem cells can be divided into two general groups. The first is embryonic stem cells, which are pluripotent in nature, meaning they can turn into cells that will contribute to any kind of tissue. These are very powerful stem cells that can replicate an unlimited amount of times and differentiate into almost all cells of the human body. In theory, and in terms of research and medicine, this type of stem cell holds the most potential. However, in practice, embryonic stem cells have caused a lot of problems in the medical community. One big problem is ethics, because to get embryonic stem cells, one needs an embryo, which until now has required taking the entire blastocyst (which is the term for the embryo after day 5, when it is typically composed of 70-100 cells), as opposed to taking a few cells and leaving the rest to continue growing. Of course, to take the entire embryo is to take what could have been a human life, which is argued by many to be unethical. Ethics aside, however, another huge problem with embryonic stem cells is that once they are removed from the embryo, they seem to lose their sight of an end goal. Tasked with creating a baby, they sometimes continue toward this goal, but in a more confused manner. As a result, they continue to multiply and regenerate endlessly, creating a confusing mass of different types of tissue called a teratoma. When used as a treatment, they can create large tumors that do much more harm than good. In fact, most (if not all) stem cell treatment complications are a result of using embryonic stem cells. This has unfortunately created an undeserved reputation for the whole stem cell community.

Adult Stem Cells are safe and effective

The other group of stem cells are adult stem cells (also called somatic stem cells), which stay with us throughout our lives. They can be multipotent, oligopotent, or unipotent, and have the ability to divide into any type of cell that might be needed within a specific tissue. Their main responsibility is to maintain and repair their assigned tissue. So far, these adult stem cells have proven to be the most useful when it comes to treatment for one main reason– they do not share the risks of embryonic stem cells, and have been proven to be completely safe. Unlike their embryonic counterparts, adult stem cells have a limited capacity to multiply. No study has ever shown a correlation between adult stem cell treatments and cancer. At Beike, none of the 22,500+ patients that have been treated with Beike stem cells have ever developed cancer due to the stem cell treatment. In fact, researchers are currently finding ways to use some adult stem cells to target cancerous tumors and treat cancer patients. 

Stem Cells and Cerebral Palsy 

There have been many studies done on cell therapies for cerebral palsy, and clinical trials have shown that stem cells have been effective in improving CP symptoms. One of the most impressive studies to date is from Duke University in the United States. Duke conducted a randomized study of 63 CP children with different varieties and severities of spastic cerebral palsy. The children’s parents had placed their child’s cord blood stem cells in a blood bank after birth, and after the children were treated with their own cord blood cells, they were shown to see improvements in their motor function just a year later. These improvements were better than those of other CP children of similar age and condition, and better than those that were given fewer stem cells or none at all. One of those children’s stories can be seen here. Senior author of the study Joanne Kurtzberg, M.D., is the director of Duke’s Pediatric Blood and Marrow Transplant Program and the Robertson Clinical and Translational Therapy Program. She says, “previous research has indicated it’s safe for children with cerebral palsy to receive an infusion of their own cord blood. Now that we have identified a dosing threshold, we are planning additional studies testing the benefits of multiple doses of cells, as well as the use of donor cells for patients whose own cord blood was not banked.” The study has been approved by the National Institute of Health (NIH) and was published in 2017. This has been considered a breakthrough in medicine, and though we still have more to learn about the detailed mechanism by which CP patients improve, we understand how stem cells can restore brain function and it is clear that neurological function can and does improve, leading to improvements in all kinds of CP symptoms.

Umbilical cord derived stem cells

One of the most promising stem cell treatments come from umbilical cord-derived stem cells, including mesenchymal stem cells (MSC), hematopoietic stem cells (HSC), endothelial progenitor cells (EPC), and others. These adult stem cells are able to differentiate into different types of cells, such as osteocytes (bone), chondrocytes (cartilage), myocytes (muscle), fibroblasts (tendon/ligament), adipocytes (fat), hepatic stellate cells (liver), endothelial cells (blood vessels), all blood cells, connective tissues and more. These cells are now even found to create neurons and glial cells. These cells are also able to release products such as cytokines and growth factors that contribute to neural protection, and when injected into the brain can stimulate the body’s own repairing of damaged neural cells. 

The collection of stem cells for treatment can be done in many ways. It could come from fat, bone marrow, umbilical cords, and more. It could come from the patient’s own body (autologous) or from a donor (allogenic). For CP patients, the most common method of injecting stem cells for treatment is either through an intravenous infusion into the bloodstream (an IV), or an intrathecal injection below the spinal cord. While IV injections are a more systemic delivery aiming for cell generation in various area of the body, the spinal cord injection can help the stem cells reach the brain better. 

Where are we now? 

Though there is a lot of hope and excitement surrounding stem cell therapy, clinical trials are still working to catch up to the hype. Though there are many clinical trials that are still underway, many have already been published that show the safety of stem cells and their efficacy. 

One study recently (2018) measured the efficacy of human umbilical cord blood mesenchymal stem cell infusion for children with cerebral palsy. The study chose to use human umbilical cord blood-derived MSCs (hUCB)-MSCs) because their use encounters fewer ethical dilemmas, the cells have comparatively low immunogenicity as well as immunosuppressive ability (meaning they are less likely to produce an immune response), and they have a higher rate of proliferation. Furthermore, because both stem cell therapy and rehabilitation have shown positive results and is the most commonly preferred option, this combination method was used for the study as well. The graphs of the changes in the Gross Motor Function Measure (GMFM-88) score (the measurement tool for severity of CP in terms of motor function) and the comprehensive functional assessment (CFA) score (a more comprehensive measurement that includes cognizance and comprehension) can be seen in the graphs below. 

It can be seen from the graphs that the more comprehensive scale of measurement, the CFA, showed stronger improvements, telling us that stem cells strongly influence cognitive function as well:

The full study can be found here.

Patients that received stem cells had the greatest cognitive and motor improvements

There was another study done by the Sung Kwang Medical Foundation in 2011 that found efficacy in stem cell treatments for children with CP. They studied three groups of children with CP: one group received rehabilitation therapy only, one received rehabilitation therapy with erythropoietin (a drug shown to have promise in treating CP), and one group received rehabilitation therapy, erythropoietin, and cord blood stem cell injections. The study showed the patients that received stem cell treatments had the greatest cognitive and motor improvements. Other studies are still being done or assessed and will hopefully provide more promising evidence for the use of stem cell therapy in the future. 

How stem cell treatment helped patients with CP

In our Follow-Up Program, we send questionnaires to patients at regular intervals after a treatment in which we ask about the success of the treatment. We can then anonymously break down this data by diagnosis and thus obtain an overview of how well the treatment works for the various clinical pictures. To illustrate the success of our stem cell treatment for CP, the following graph shows the improvements families with CP patients have stated in our follow-up questionnaires.

Another point of measurement for treatment success is the basic question, if the families believe that stem cell treatment did in fact improve quality of life for the CP child.

The last datapoint is the very subjective question, if patients are satisfied with the treatment outcome.

For a more personal close up at what our patients’ experiences are like, here are two patients that received stem cell treatment and their stories:

Renzo Centurion:

Renzo was diagnosed with cerebral palsy after he suffered hypoxia, a lack of oxygen, at birth, causing a hemiparesis in his right side. Though his parents tried to help him, his improvement plateaued at just 6 years old. He was still unable to dress himself, and largely unable to move his right arm and hand. After receiving stem cells through intravenous injections, he began to notice improvements after just 15 days. Now, he has much better control over his right side, and can hold a glass of water and write. He can dress himself, lift his arms above his head, and his endurance has increased enough to be able to walk two or three kilometers. See his improvements in the video below:

Flynn Rigby: 

Flynn was born at 23 and a half weeks, which is extremely mature, affecting his fine motor skills and speech. At 9 years old, he was still unable to speak, until after his first stem cell treatment. He has since started talking, improved his general fine motor skills, and even shown an improvement in his reading comprehension and social interactions. See Flynn’s progress below:

Conclusion

Cerebral palsy is a condition that affects a large number of people, with data showing anywhere from 2-3 people per 1000. It can affect people in minor, almost unnoticeable ways, or it can be debilitating. While it is currently an incurable condition, stem cells offer hope to people that might otherwise have none. Current research and treatment has shed light on the potential of stem cells as a method of treatment and therapy, as we know that it can and does help people with CP. However, as we do not completely understand the mechanism by which stem cells heal, further research will help us understand that system and, through that understanding, find ways to unlock the potential of stem cells and better help patients.