A clinical trial concludes that while lithium carbonate appears to be safe, it is ineffective at treating amyotrophic lateral sclerosis (ALS), a type of motor neuron disease (MND) that is also known as Lou Gehrig’s Disease.
The trial investigators, led by King’s College London’s Institute of Psychiatry, report the results of the LiCALS trial in the April print issue of The Lancet Neurology, which was published online at the end of February.
ALS is a neurodegenerative disease where the motor neurons, the nerve cells that control muscles, in the brain and spinal cord waste away. The result is muscles fail to receive signals instructing them to move, causing them to weaken and twitch, leading to increasing paralysis.
When the muscles in the chest stop working, the patient becomes dependent on a mechanical ventilator, and death usually occurs within 3 years.
ALS affects about 5 out of every 100,000 people worldwide.
There is no known cure for ALS. A drug called riluzole helps slow down the symptoms and improves survival in patients with ALS, but the effect is moderate, so there is a great need for better treaments.
Research on animals suggests that lithium may offer some protection against the degeneration of nerve cells seen in ALS.
The LiCALS trial’s chief investigator is Ammar Al-Chalabi, professor of Neurology and Complex Disease Genetics, at King’s College London, and also of the College’s Institute of Psychiatry. He says in a statement released earlier this week:
“A previous small study showed that lithium might slow down ALS and improve survival rates, but the result was not certain. What was needed was a definitive trial to show whether or not this was an effective treatment for patients with ALS.”
The trial involved 214 patients with ALS who were being treated with riluzole.
The patients were randomly assigned to a treatment group (107) that received daily doses of oral lithium, or a placebo group (107) that received daily doses of a dummy drug. Both groups were followed for 18 months.
The results showed no significant increase in survival rates for the treatment group compared to the placebo group, although the drug was found to be safe.
When lithium was first put forward as a potential therapy for MND, and a couple of small trials showed it didn’t have immediate benefit, there was hope that a larger, longer trial might show it has longer term benefit, as proved to be the case with riluzole, using survival as the primary measure.
But, as Brian Dickie, Director of Research Development at the MND Association says while the result is “deeply disappointing, we now have a clear answer”.
Al-Chalabi says although the LiCALS trial results are disappointing, it has left a valuable legacy. There is now a network of ten centres in the UK that are geared up for rapid testing of future potential therapies.
“We are most grateful to the patients who took part in the trial and not only helped answer the question of whether lithium could treat ALS, but also helped in establishing a trials network,” says Al-Chalabi.
“We will continue our search for novel treatments for this devastating disease,” he adds.
Funds from the Motor Neurone Disease Association (MNDA) helped finance the trial, which was coordinated by the National Institute for Health Research (NIHR) DeNDRoN (Dementias and Neurodegenerative Diseases Network).
Earlier this month, researchers writing in the journal Nature, describe finding two mutated genes that lead to the destruction of nerve cells in ALS, and how these same mutations also appear to be linked to the development of other related degenerative diseases.
Written by Catharine Paddock PhD