Cerebral Palsy: how could stem cells help?
Cerebral palsy affects approximately two in every thousand children in Europe, and is the most common physical disability in childhood. It causes a wide range of physical symptoms, which include difficulties walking and coordinating movements. No cure has yet been discovered. So could stem cells help?
Cerebral palsy is a group of physical and mental disabilities that are caused by damage to a child’s developing brain during pregnancy or shortly after birth. In many cases the exact cause of brain damage is not known.
Patients with cerebral palsy often have difficulties speaking, moving, eating, and controlling eye movements; some patients also have learning disabilities.
There is no cure for cerebral palsy. Therapies focus on helping patients deal with symptoms and improving communication. Some medications are available to help patients relax stiff muscles and address feeding problems in babies.
Studies are only in very early stages of examining how stem cells might be used to treat cerebral palsy.
There are currently no approved stem cell treatments for cerebral palsy.
Researchers think neural (brain) stem cell treatments might be help to restore some function to patients. Transplants of neural stem cells or drugs that activate natural neural stem cells could repair and replace neurons and other supporting brain cells.
Mesenchymal stem cells (MSCs) cannot make new brain cells, but some preliminary studies suggest MSCs release substances that promote natural brain repair processes.
Each case of cerebral palsy is unique, making understanding the causes and implications of this disability very difficult.
The developmental process of the brain in humans and animals are incredibly different. This makes studying and testing new treatments for brain developmental disorders exceptionally difficult and results found in animals may not translate to humans.
Using stem cells to rebuild the brain of cerebral palsy patients will be incredibly challenging because new cells and neurons will have to be correctly wired into complex networks of thousands of other neurons in the brain.
Cerebral palsy is an umbrella term for the effects of damage to a developing brain by various causes. It is connected with a range of symptoms, including muscle weakness and movement problems. The damage to the brain usually occurs early on in its development, either in the baby during pregnancy or during the period soon after birth. Symptoms may include difficulties in walking, balance and motor control, eating, swallowing, speech or coordination of eye movements. Some people affected by cerebral palsy also have some level of intellectual disability. No two people with cerebral palsy are affected in exactly the same way.
Each child is unique, and cerebral palsy takes different forms depending on which area of the brain has been damaged. Doctors usually make a diagnosis after looking at the brain injury using an MRI brain scan and considering the patient’s most dominant movement problem. They also monitor the child through developmental milestones such as sitting, crawling, walking. There are four main types of cerebral palsy: spastic, dyskinetic, ataxic, or mixed when the patient has more than one movement disorder. Spastic cerebral palsy is the most common form, accounting for around 80% of all cases. This type typically involves muscle tightness, which makes movement difficult and can affect speech and bladder control. It can affect part or all of the body. Many patients with spastic cerebral palsy also have some involuntary movements and are therefore referred to as mixed. Dyskinetic cerebral palsyaccounts for 10-15% of cases, and is often one of the most severe forms of cerebral palsy. It causes involuntary movements, changes in muscle tone and also affects posture and/or movement. Ataxic cerebral palsy accounts for around 5% of cerebral palsy, and affects fine coordination of movements, for example balance, posture, gait, control of eye movements and depth perception.
Cerebral palsy may arise during pregnancy, but can also be caused by complications at birth, or following injury or illness after birth. It is often difficult to pinpoint exactly what has caused the damage to the brain because many different things can work together to create each person’s unique set of symptoms, including:
- Changes in the genes inside the brain’s cells can affect how the brain develops
- The brain can sometimes develop in an unusual shape or structure
- Infections during pregnancy or physical injury can cause damage to the brain
- Complications of premature birth
- Critical illness at birth (known as neonatal encephalopathy), which sometimes causes a shortage of oxygen to the brain
Today’s therapies focus on making the symptoms of cerebral palsy more manageable. There is no cure, but teams of healthcare professionals work together with the patient to tackle the different aspects of their cerebral palsy. This might include physiotherapy and occupational therapy to improve movement and mobility, as well as speech therapy to improve communication skills. Muscle relaxants are available to tackle muscle stiffness, and other medicines are available to help with feeding problems in babies. A number of specialist organisations provide support for families and information on available therapies.
Research into stem cell therapies for cerebral palsy is still at a very early stage and no treatments are currently available. Various new strategies are being explored using stem cells, but it is unlikely that any of them will offer a full cure. Instead, they aim to limit the damage to cells in the brain and reduce the symptoms. Cerebral palsy is so difficult to treat because it can involve damage to many different types of cells in the brain. Severely damaged cells can be lost completely. Scientists expect that future treatments will aim to protect and repair damaged brain cells before they are entirely lost. This means it is likely that any new treatment will have to be applied within a small window of time, between the initial injury that has caused damage and the onset of permanent cell loss.
Today, researchers are using several different types of stem cells to study brain injury in animals and to explore the possibilities for developing new treatments. In some of these studies, researchers do appear to have been able to reduce damage to the brain and the animals have shown some improvements in their symptoms. However, these effects in animals are not yet fully understood, and what happens in animals in the laboratory is never an exact match for what will happen in human patients. Much more work is needed and it will be many years until such research can be applied to treating cerebral palsy.
Replacing lost cells in the brain
The brain and spinal cord contain cells called neural precursor cells, which can develop into the specialised cells of the brain. One idea is that these neural precursor cells could be transplanted into cerebral palsy patients or used to make new nerve cells in the lab to replace lost cells in the patient’s brain. However, if this turns out to be possible, it is an extremely long-term goal. Any new cells transplanted into the brain would need to connect correctly with the complex network of thousands of interconnected cells carrying signals around the brain. This is hugely challenging and carries serious risks, so researchers believe other approaches will provide results sooner.
Injection of stem cells to help protect or repair damaged nerve cells
Research is underway to investigate a number of different types of stem cells for this purpose:
Neural precursor cells from the brain and spinal cord are being investigated in animals as a tool for supporting damaged tissues in the brain. A study using rats, in which neural precursor cells were injected into the brain after an injury, found that the injected cells released chemicals that helped damaged nerve cells to survive. Permanent damage to nerve cells could be prevented because the injected precursor cells had protective properties, helping prevent the loss of specialised brain cells called oligodendrocytes and neurons. These early findings are now under further investigation.
Mesenchymal stem cells (MSCs), which can develop into bone, muscle and circulatory tissues, are being tested in mice to investigate their use for treating brain damage. MSCs cannot develop into brain cells, but some studies suggest that when they are injected into the brain or bloodstream of mice, they can travel to the damaged part of the brain and release substances that help support the recovery of nerve cells. Scientists are now working to understand exactly how this effect is achieved in mice, what role the injected mesenchymal stem cells played and whether this could be developed into a safe and effective approach to treating human patients.
Umbilical cord blood stem cells can be collected from the umbilical cord shortly after birth. These cells have been proven to be very useful for treating certain blood cancers such as leukaemia. They are currently being tested as a potential treatment for cerebral palsy and researchers hope that they may be able to support the recovery of damaged nerve cells by releasing substances that stimulate the body’s own repair systems.
Using stem cells to study how cerebral palsy works
Embryonic stem cells and induced pluripotent stem (iPS) cells are both types of stem cell known as pluripotent. This means they can turn into any type of cell in the body. They are currently being used to produce different types of specialised brain cells in the lab in order to study how cerebral palsy works. This is a very important tool for researchers in their effort to identify new possibilities for treatments. Induced pluripotent stem cells can be created from the skin cells of a patient and used to produce nerve cells that have the exact same genes as the patient. This makes them powerful for studying the roles of certain genes in the disease. In theory, iPS cells could also be used to produce nerve cells for transplantation back into the patient without a risk of rejection, since the cells are made from the patient’s own skin. However, no cells are yet being produced from iPS cells for transplantation into cerebral palsy patients, and much more work is needed to determine whether this may be a possibility in the future or not.
Developing drugs to target the stem cells already present in the brain
Our brains contain stem cells capable of making the nerve cells of the brain. A possible route for treating cerebral palsy would be to develop drugs to encourage a patient’s own stem cells to become more active and to repair damaged tissue. Researchers hope studies on brain stem cells and nerve cells in the lab will help identify the kinds of drugs that could be useful for this purpose.
No. Research into potential stem cell therapies for cerebral palsy is still at the stage of laboratory studies and some very preliminary clinical trials, so no proven treatment is currently available. Current clinical trials typically involve injection of stem cells from the bone marrow or umbilical cord blood into the brain. Although measurements are taken of any changes in the patients’ control of their movement, the main focus of such early trials is to find out whether this type of treatment is safe. Current trials are listed in the registry clinicaltrials.gov. It is likely that a combination of treatments will be needed for cerebral palsy patients, making use of the benefits of stem cells, physiotherapy and other approaches. Many questions must be answered by further research before stem cell treatments can become a reality, for example:
- Which of the various types of stem cells would be the best to use?
- How can we obtain the cells we need in large quantities?
- What is the best way in which to use these cells and how will they affect the body?
- If we plan to inject cells, should they be injected directly into the damaged area of the brain, or into the bloodstream?
- When does the treatment need to be given for the best result, i.e. is there a window of time after which the damage becomes permanent?
- Is a treatment that stimulates the stem cells already within the brain a better solution?
The safety of any treatment also needs to be established through many stages of research to reduce the risk to patients. For example, a particular safety issue with stem cells is that they are highly capable of dividing and multiplying, meaning they have the potential to form cancerous tumours. Scientists therefore need to know exactly how the stem cells will behave when used as a treatment, and this will take time.
Although you may find clinics offering stem cell therapies for many different diseases, there are no stem cell therapies for cerebral palsy that have been proven safe and effective. If you are offered a stem cell treatment, consult your doctor and read Considering a stem cell treatment offer? for additional advice.
Image of a mother and her daughter with cerebral palsy by Libby Welch, Wellcome Images. Image of neural precursor cells differentiating by Nina Callard, Wellcome Images. Illustration showing examples of nerve cells found in the brain created by Nia Powell using Servier Medical Art.