Alzheimer’s disease is caused by cell death in several areas of the brain. It is a progressive disorder that leads to loss of memory and cognitive abilities. Ultimately, Alzheimer's is fatal.  There is currently no cure.

Damage to the brain in Alzheimer’s disease is widespread, making stem cell-based approaches to treatment problematic. Stem cell therapy offers greatest potential for diseases in which specific, well-known types of cell need to be replaced or helped to function correctly. In Alzheimer's disease several different groups of brain cell would need to be replaced, and scientists believe it is highly likely that the signals needed to help transplanted cells integrate into the brain may be absent in the Alzheimer brain.

Stem cells could, however, be genetically modified so as to deliver substances to the Alzheimer brain, to stop cells from dying and stimulate the function of existing cells. A recent clinical trial (Phase I) has shown this approach to be of some benefit to patients with Alzheimer’s disease, by slowing down the progression of the disease.

Relevant links:
alz.org - alzheimer's association research center - good information on the status of current research, future directions and clinical trials
Alzheimer's Society (UK)
Alzheimer Europe

Huntington's Disease (HD) is a hereditary, degenerative brain disorder for which there is currently no cure.  

Huntington's disease is caused by a faulty gene on chromosome 4. This gene, which produces a protein called Huntingtin, was discovered in 1993. In some way - which is not yet fully understood - the faulty gene leads to damage of nerve cells in areas of the brain including the basal ganglia and cerebral cortex.  This leads to gradual physical, mental and emotional changes.

Each child of a parent with Huntington's disease has a 50:50 probability of inheriting the faulty gene. Anyone who inherits the faulty gene will, at some stage, develop the disease. It typically becomes noticeable in middle age.

Stem cells could be useful in the quest to develop treatments for Huntington's disease on a number of fronts:

1. Stem cells could be used to study HD, as a supplement to animal models of the disease.  For example, cell lines that carry the faulty gene have been generated from induced pluripotent stem cells, providing a new model to study the development of Huntington's disease in the laboratory. These cell lines could also be used to screen for and test potential new treatments.  For more information about the creation of disease-specific cell lines, see our iPS cells fact sheet.
2. It may be possible to stimulate the brain's own production of stem cells to help replace cells affected by the disease.
3. Stem cells could be introduced into the brain with the hope that they would replace dead and dysfunctional cells - either as a primary treatment or  to restore brain cells lost in Huntington's disease following treatment(s) to halt disease progression.  While this is a promising avenue of research, more work needs to be done to understand the factors that control the differentiation, survival, and maturation of stem cells in a brain affected by HD before this kind of therapy can be transferred to the clinic.

Relevant links
European Huntington's Disease Network - a platform for professionals and people affected by HD and their relatives to facilitate working together throughout Europe
NIH page on Huntington's disease
Huntington's Disease Society of America
Hereditary Disease Foundation
HOPES: A guide to the science of Huntington's disease - a student-run project at Stanford University dedicated to making scientific information about Huntington's disease more readily accessible to patients and the public
Summary of Huntington's Disease research - provided by NCBI (the National Center for Biotechnology Information) - more technical

In motor neurone disease (known as amyotrophic lateral sclerosis in the USA, sometimes also called Lou Gehrig’s disease) nerve cells that control movement, located both in the spinal cord and in the brain, degenerate and die. As a result, the muscles to which those nerve cells were connected eventually weaken and waste away. Patients lose their strength and the ability to move their arms, legs and body. Eventually the muscles in the diaphragm and chest wall fail, and the patient becomes unable to breathe without support.

Because nerve cells in both the spinal cord and the brain are affected in motorneuron disease, the prospect of treatment through replacement of these cells seems a distant goal. Any effective cell-replacement therapy would have to restore the function of both groups of nerve cells, and, as with other neurological disorders, ensure that the new cells become integrated into the existing circuits, so that the brain and spinal cord are able to function appropriately. For all these reasons, scientists feel that a great deal of laboratory research should be done before moving into clinical trials involving motorneuron disease patients.

Scientists believe that a more realistic approach is to use stem cells to alleviate the symptoms and even revert progression of the disease. When transplanted into the spinal cords of animals with motorneuron disease, stem cells appear to nurse the sick and injured nerve cells, preventing them from dying and improving their function. Scientists are hopeful that within the next few years they will know enough to test these treatments in patients, which they expect to be most helpful if administered shortly after diagnosis, when a patient begins to lose limb function but before paralysis sets in.

Relevant links:
ALS Association
The National Institute of Neurological Disorders and Stroke
Motor Neuron Disease (MND) Association
MND Scotland

The myelin layer (concentric) surrounds the axon of a neuron: Wikimedia CommonsMultiple sclerosis is an inflammatory (auto)immune-mediated disease in which the patient’s immune system destroys the protective sheath (called myelin) that envelops and protects the nerves. As a result, the flow of information in the brain and spinal cord is interrupted. Ultimately, the actual nerve cells are affected and die. Patients with multiple sclerosis show a variety of symptoms involving the central nervous system, including spasms, difficulty walking, bladder and bowel problems and fatigue.

This BBC news clip explains what happens in MS, and outlines one stem-cell-based approach to developing a treatment for the disease.

There are two concurrent components to any successful therapeutic approach to multiple sclerosis:

1. to prevent damage to the central nervous system by interfering with inflammation caused by the immune system’s attack on the nerves;
2. to repair the existing damage.

Stem cells are potentially useful in both components. Clinical trials have been carried out in which patients have received intensive immunosuppressive treatments followed by transplants of blood stem cells from their own bone marrow or blood. These trials aimed to block the autoimmune reaction that causes myelin and nerve damage, and they have shown some benefits: a proportion of patients did not progress in the disease, although some showed no improvement and others regressed.

Research using animal models has shown that it is possible to promote repair of the myelin (remyelination) surrounding damaged nerves by transplanting very young ensheathing cells (so-called precursor cells), made from embryonic stem cellsⁱ or adult neural (brain) stem cells. This myelin repair can be either direct or indirect. Direct myelin repair involves differentiation of stem/precursor cells into myelin forming cells. Indirect remyelination is mainly due to a ‘bystander’ effect of the stem/precursor cells, in which the cells release molecules capable of suppressing inflammation, providing support for the development and growth of nerves, promoting the formation of new blood vessels, and/or reducing nitric oxide-mediated nerve damage.

Apart from stem cell transplantation, scientists know that in the early stages of multiple sclerosis the existing myelinating cells are able to offer some spontaneous remyelination. An important area of research is focused on finding ways to enhance remyelination from these cells.

Relevant links:
The European Multiple Sclerosis Platform
The Multiple Sclerosis Society
Multiple Sclerosis Trust
The National Insitute of Neurological Disorders and Stroke

Parkinson's disease occurs as a result of a gradual loss of a specific type of nerve cell, located in an area of the brain called the substantia nigra. These nerve cells produce a natural chemical called dopamine (they are called dopaminergic neurons). The lack of dopamine makes patients with Parkinson’s disease have difficulty in moving freely, holding a posture, talking and writing.

Stem cell-based therapies for Parkinson's disease are not yet a routine clinical procedure. Scientists are agreed that more information is needed about the causes of Parkinson’s disease and the biology of stem cells before safe, effective and long-lasting therapies can be developed.

Because a single, well-identified type of cell is affected in Parkinson’s disease, stem cells offer great potential for treatment. The basis for such treatment would be to replace the cells that have died with other identical dopaminergic neurons. These dopaminergic neurons can readily be obtained from embryonic stem cells in the laboratory, but there are still ethical and technical hurdles to using this source.

Dopaminergic neurons can also be obtained from fetal brain tissue. You may be aware of clinical trials where fetal brain tissue was transplanted into the brains of Parkinson's disease patients. These trials provide proof-of-principle for the approach, since in a few of these trials major and long-lasting improvements were seen in some patients. The trials also emphasized several issues that need to be resolved, one of which is the need to produce large amounts of pure, uniform cells for transplantation into patients. Recent findings also highlight a further concern about cell transplantation therapies. The fetal transplants that some patients received began to show signs of being affected by Parkinson's disease. This showed that the disease from the patient was transmitted to the transplanted fetal cells.

Stem cells could also help Parkinson's patients by contributing to the discovery of new drugs, which would have a much wider impact than cell therapies. We can now get embryonic-like stem cells from adults through a method called "reprogramming". By reprogramming a sample of adult, specialised cells from a patient, we can make so-called induced pluripotent stem (iPS) cells. These iPS cells can make any type of cell found in the body, including dopaminergic neurons. Scientists are now making iPS cells from people with Parkinson’s disease and using them to produce neurons in the laboratory. The aim is to learn more about why these nerve cells die in Parkinson's disease, and to use the cells to test for substances that could be developed into new drugs.

Relevant links:
Michael J. Fox Foundation
Parkinson’s UK
The National Institute for Neurological Disorders and Stroke
European Parkinson’s Disease Association

Stroke is caused by a blockage of the blood supply to a region of the brain (ischaemic stroke) or when a blood vessel in the brain bursts, spilling blood into the spaces surrounding brain cells (haemorrhagic stroke). Brain cells die when they no longer receive oxygen and nutrients from the blood or there is sudden bleeding into or around the brain.  Depending on the area of the brain that is affected, several functions may be impaired, including walking, talking and cognitive ability.

Stem cells are not currently used for treatment of stroke. Cells from fetal brain, bone marrow, umbilical cord blood, and embryonic tumours have yielded some improvements when transplanted into animal models of stroke. In a clinical trial in which patients received implants of nerve cells generated from a human embryonic tumour, some of the patients showed short-term improvements. In most of these cases, the transplanted cells acted by releasing substances that enhanced the survival of existing cells.

One of the favoured approaches to long-term, effective stem cell therapy for stroke is to transplant neural (brain) stem cells into patients. Ideally, these cells, generated from either embryonic or fetal brain stem cells, would then specialize into the cells that have died in the affected area of the brain. In several studies using animal models the new cells were able to move to the affected area, replace the dead cells, survive, connect to existing healthy cells and re-establish the damaged circuits of the brain. 

In January 2009, UK company ReNeuron announced it had UK regulatory approval to start a Phase I clinical study of its neural stem cell treatment, which is designed to regenerate portions of the brain impaired by ischaemic stroke. The trial will test the safety of this treatment, which involves the injection of cells from derived from human fetal tissue directly into patients' brains. Read more about this trial, which is now under way.

Another approach to stem cell therapy for stroke could be to stimulate the stem cells naturally present in the brains of stroke patients, so that they could generate replacements for the dead cells. Scientists are testing several substances for their effect on stimulating the existing stem cells.

Relevant links:
European Stroke Network - collaborative EU effort that brings together researchers, government, industry, the non-profit sector, and patient group associations. Puts Europe at the forefront of stroke research through its multi-disciplinary research program, high quality training for European scientists and clinicians, and national and global partnerships.
Stroke Alliance for Europe - listing of European patient organizations
European Stroke Organization - searchable listings of national stroke groups
The Stroke Association
The Stroke Trials Directory of the Internet Stroke Center
The National Institute of Neurological Disorders and Stroke
Stroke Facts - from the World Stroke Campaign (also available in Spanish)

Umbilical cord blood contains haematopoietic (blood) stem cells. These cells are able to make the different types of cell in the blood (red blood cells, white blood cells and platelets). Hematopoietic stem cells are also found in bone marrow. Umbilical cord blood is seen as a good alternative source of haematopoietic stem cells, since it is easily accessible. Indeed, umbilical cord blood has long been used in stem cell treatments for leukaemia, several blood disorders and immune disorders, particularly in children.

Despite the many reports of multiple sclerosis patients (and others) being successfully treated with cells from umbilical cord blood, clinical trials have not been undertaken to properly determine the safety and efficacy of these treatments and scientists agree that several problems need to be overcome before umbilical cord stem cells may be used in this kind of therapy.

For example, in order to be useful for long-term treatments of neurological diseases, the stem cells in umbilical cord blood would have to efficiently replace the cells of the nervous system that are lost as a result of the disease. A first step would be to direct umbilical cord blood stem cells to become functional nerve cells in the laboratory, however, to date, there is no compelling evidence that this is possible.