Cell‐based therapies for amyotrophic lateral sclerosis/motor | Figure 1

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Cell‐based therapies for amyotrophic lateral sclerosis/motor neuron disease

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Review question

How effective and safe is cell‐based therapy in people with ALS/MND, when we compare it with an inactive treatment or no treatment?

Background

Amyotrophic lateral sclerosis (ALS; also known as motor neuron disease or MND) is a condition in which nerves in the brain and spinal cord that control movement (motor neurons) stop working. A person with ALS/MND has difficulty moving, swallowing, chewing and speaking, which become worse over time. Half of people with ALS/MND die within three years of their first symptoms. Weakness of muscles used in breathing often leads to death. The condition currently has no cure. Current treatment approaches largely focus on relieving symptoms to improve the quality of life of those affected.

Cell‐based therapy can be defined as injection of cellular material into a person to treat disease. Various types of cell‐based therapies have been tried in ALS/MND, including stem cell therapy. Stem cell therapy aims to provide new motor neurons, which may help stop or slow down disease progression in people with ALS/MND. Previous reviews supported the use of cell‐based therapy as a potential means of delaying the disease course in ALS/MND, but these were mainly based on preclinical animal models. Randomised controlled trials (RCTs) provide the most reliable evidence. In RCTs, one group receives the test treatment, and the other, 'control' group has an alternative treatment, a dummy treatment (placebo) or no treatment. Well‐performed RCTs provide the best evidence. Studies with no untreated group for comparison and small clinical trials have found no clinical benefits. Limited data from non‐RCTs involving a small number of people with ALS/MND and a short follow‐up period suggested that cell‐based therapy may slow disease progression. There is currently no approved cell‐based therapy for ALS/MND. We undertook this review to assess the RCT evidence now becoming available.

Study characteristics

Cochrane review authors searched medical databases for clinical trials. They found two completed RCTs that assessed the effects of cell‐based therapy over a six‐month follow‐up period. One study was not fully published and did not provide numerical data. Both studies were funded by stem cell companies. One study, which included 64 people with ALS/MND, provided data. The people taking part in the trial had an average time since symptom onset of about two years. They had mild to moderate problems with motor function (ability to perform physical tasks) at the start of the trial (with an average of 35 on the ALS Functional Rating Scale‐revised, on which a score of 0 indicates greatest impairment and 48 is normal function).

Key results and quality of the evidence

The study provided low‐quality evidence that stem cells obtained from people's own bone marrow (the cells in the centre of bone) did not result in significant side effects. The cell implantation procedure was well tolerated. Based on evidence from this trial, stem cell treatment may slightly reduce decline in motor function at six months, but may not improve breathing or quality of life at four months, or overall survival at six months. Based on the very limited evidence available, any benefit is uncertain due to there being only one poorly conducted study and results within the study varies. We urgently need large, well‐designed clinical trials to establish whether or not cell‐based therapies have a clear clinical benefit in ALS/MND. Major goals of future research are to identify the right type and amount of cells to use, and how best to administer them.

The evidence is up to date as of July 2019.

Read the full Cochrane Review here

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