Stem cell therapy for refractory epilepsy

By Dr Steven White, Consultant Neurophysiologist, Cromwell Hospital, London

Epilepsy is one of the commonest serious neurological disorders, estimated by the World Health Organization (WHO) to affect around 50 million people worldwide. While many will respond well to medication, around 30% will continue to have poorly controlled seizures despite treatment. Recent research has suggested that stem cell therapy may have potential as a novel intervention for refractory epilepsy. Work in this area is still at an early stage, but it was reviewed positively but realistically in a recent article from China. Epilepsy has many potential causes, one of which is encephalitis, so that this topic will be of interest to the Encephalitis International community.

What are stem cells?

Stem cells are unique, in that they are unspecialised but have the potential to develop into the different kinds of specific cells which make up the tissues and organs of the body, ranging from heart muscle or blood cells to brain cells. They can be guided into becoming specific types of cell, which may then be used in stem cell therapy to target a number of medical conditions.

How does stem cell therapy work?

Stem cells are harvested either from the patient’s own body (autologous) or from a donor (allogeneic). They are manipulated in the laboratory to differentiate into specific types of cell, which can then be implanted to help replace or repair diseased or damaged tissue and promote the growth of neighbouring cells, as well as modulating immune responses.

Some stem cell therapies are well-established, such as bone marrow transplantation for blood diseases like leukaemia and for some immune system disorders.

Stem cell therapy for refractory epilepsy

Recent advances have positioned stem cell therapy as a possible new approach for refractory epilepsy. Preclinical studies have suggested that stem cell transplantation may help through multiple mechanisms, including:

• differentiation into inhibitory interneurons, which may damp down the excessive excitation of nerve cells characteristic of epilepsy;

• secretion of neurotrophic factors such as BDNF and GDNF, which promote neuroprotection and neuroregeneration, thereby improving neural network function;

• reducing harmful neuroinflammation and modulating immune responses.

There is early evidence from small-scale clinical studies that stem cell therapy may benefit some patients with refractory epilepsy, with occasional quite striking results. More general improvements in cognition and well-being have sometimes been seen, as well as better seizure control.

However, much of the research so far has been with very mixed patient groups who have different kinds of epilepsy, or has focused on a single type of epilepsy. So it is difficult to know yet whether positive results from stem cell therapy only apply to a few specific types of epilepsy, or if it has a broader potential.

The length of follow-up has often been quite short with variable methods of assessing outcome, so it’s not yet clear how long the benefits of stem cell therapy may last.

However, it is now beginning to reach the stage of conventional larger scale controlled trials, very much of the kind which are standard in assessing the effectiveness of drugs or other treatments. The multicentre EPIC (EPIlepsy Cell therapy) trial in the United States will use human stem cell-derived inhibitory interneurons, which will be implanted directly into the hippocampus in patients with refractory mesial temporal lobe epilepsy.

The outcome of these trials will help to give a clearer picture of the potential of stem cell therapy for refractory epilepsy, but we do not yet have the answers.

Cautions and limitations

Many of the small studies have found stem cell therapy to be safe, and well-tolerated with a low rate of side effects. However, there is no doubt that some types of stem cell therapy do have the potential for very serious adverse effects in at least occasional patients. So this does need to be taken into account when considering this type of treatment.

Stem cell therapy for epilepsy may be quite an undertaking, sometimes involving injections into the cerebrospinal fluid (CSF) by lumbar puncture (LP), or direct implantation into the brain, as in the EPIC trial, so it’s certainly not an easy option.

There is no standard protocol for stem cell therapy in refractory epilepsy and different centres have used varying approaches. This means that it is not something which can be requested as a standard treatment.

Conclusion

Stem cell therapy does seem to show promise for at least some patients with refractory epilepsy, which is very welcome. However, the technique is really at an early stage of its development. We don’t yet understand what type of stem cell therapy works best, who is most likely to respond well and whether it is useful for different types of epilepsy. As well, the longer-term outcome of stem cell therapy and the true profile of serious risks vs benefit have not yet been clearly defined.

Nevertheless, stem cell therapy for refractory epilepsy is being actively researched on a worldwide basis. We hope that it may turn out to have a positive future and so it is certainly worth keeping in mind.

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Fore more information on seizures and encephalitis, click here.