The UK’s Motor Neurone Disease (MND) Association will fund a clinical trial investigating whether the standard mood stabiliser lithium could be an effective treatment for MND.

Up to 220 patients from 10 MND Care Centres across England will be recruited for the £1 million trial, which the charity hopes will start in the first half of 2009. It will be run through the National Institute for Health Research’s Dementias and Neurodegenerative Diseases Research Network (DeNDRoN), which provides a National Health Service infrastructure to support research alongside clinical practice.

The MND Association has been developing a network of care centres throughout England, Wales and Northern Ireland since 1990. There are currently 17 MND Care Centres in total. Some 5,000 people are living with MND in the UK while 100,000 people have the disease worldwide.

This is the first time the MND Association has been in a position to fund its own clinical study, it noted. Around £400,000 of the £1 million investment will come from the association while DeNDRoN is funding the service support costs of about £540,000.

At the moment, the charity noted, lithium is occasionally prescribed to people with MND to treat accompanying or pre-existing disorders. However, online MD communities “are now aware of the possible effects of lithium in slowing the disease – and within some patient-group forums, members with the disease are asking how they can obtain lithium without prescription”.

Italian study

As the MND Association noted, laboratory studies have shown that lithium can have a protective effect on motor neurones and the drug has produced positive effects in the mouse model of MND. Moreover, in February Italian researchers published the results of a small clinical trial suggesting that lithium could slow the progression of MND.

The Italian team led by Francesco Fornai from the Department of Human Morphology and Applied Biology at the University of Pisa conducted a parallel-group, randomised study of lithium in amyotrophic lateral sclerosis (ALS), which is the most common sub-type of MND. Out of 44 adults with ALS, 16 were randomised to the approved treatment riluzole (Rilutek) plus lithium, and the remainder to riluzole alone.

According to the results published in the US journal Proceedings of the National Academy of Sciences, after 15 months no deaths had occurred in the 16 patients treated with riluzole plus lithium, whereas 29% of the riluzole-only group had died. Disease-related disability was also markedly less pronounced in the riluzole-lithium patients.

Based on these promising but inconclusive findings, a North American consortium including the ALS Association in the US, the ALS Society of Canada and the US National Institutes of Health/National Institute of Neurological Diseases and Stroke announced in September that it would fund a double-blind, placebo-controlled trial with 84 early-stage ALS patients at sites in the US and Canada.

These patients will be randomised to either lithium or placebo. Once the 84th participant has been enrolled, a decision will be taken on whether to expand the trial to 250 patients. The UK study will run in parallel to this trial. “It is necessary to conduct both of these trials due to the requirement to repeat experiments to ensure that the results obtained from both trials are correct,” the MND Association commented. “The results found will also be comparable and therefore will provide us with more data, quicker.”

The MND Association said the results of the Italian trial were encouraging but should be treated with “extreme caution” as the study had significant weaknesses. Moreover, noted the association’s director of research and development, Dr Brian Dickie, lithium “can affect several chemical processes in the body, with the potential to cause side-effects. It is therefore essential that all patients involved in this trial are very carefully monitored”.

Nonetheless, commented Professor Nigel Leigh, the director of the King’s MND Centre at King’s College London who will spearhead the UK trial, the Italian outcomes are “too dramatic to ignore … We need to know the truth about lithium and we have a robust trial which will deliver real answer”.

The UK study will be a randomised, double-blind, placebo-controlled trial in which patients will take lithium once a day for 18 months. The inclusion criteria will include: age over 18 years; a diagnosis of ALS according to World Federation of Neurology criteria; between six months and three years since the onset of symptoms; on riluzole therapy for at least four weeks; respiratory function of forced vital capacity greater than 60% of predicted; and able to understand fully study information and provide informed consent.

In the US, a “small but significant” number of people with MND are managing to obtain lithium from their doctors, “but they are taking markedly different doses and are not being closely monitored under trial conditions”, Dickie pointed out. “At the moment the answer to whether lithium is having any positive impact on the disease is getting lost in the hype and noise.”