Treatments Trials

A number of trials across the world have been completed and some are still in progress. People with MND and their carers play the most important role in the successful completion of a trial; without their support and commitment these trials couldn't be carried out. The MND Association is able to contribute to the funding of MND clinical trials in the UK as well as being able to provide information on specific drug trials. We also liaise with those running the trials to ensure, as far as possible, the needs of people with MND are paramount when designing and carrying out trials.

While the results of previous clinical trials have been largely disappointing, a great deal has been learnt: about how trials should and should not be carried out, and the questions to be answered over the  efficacy of these particular products, leading the way to future trials.

It is important to remember that trials are NOT treatments but scientific experiments. Due to the design of clinical trials participants may not receive the new drug under investigation and may experience some side effects. Research Information Sheet D - Clinical trials (253 kb)  can provide you with more information on what clinical trials are and how they are organised.

Some of the more recent trials are listed below. Details of trials taking place in all diseases are available from the American government's clinical trials website.

This trial will involve up to 220 people with MND at 10 centres across England and is currently recruiting participants. For more informaiton on this trial, please download our  information sheet Res Inf M: Lithium Questions and Answers (119 kb) . The MND Association has agreed to fund  this trial.

In laboratory studies, lithium has been shown to have protective effects on motor neurones; it has also shown some promise in animal models of MND. In early 2008, Italian researchers published apparently encouraging results from a very small clinical trial of lithium carbonate in people with MND. Read more about the Italian trial. However, the methods used in this trial had significant weaknesses and there is not yet enough evidence to say whether or not this potentially toxic drug is beneficial in MND. The current UK trial should provide more definitive answers.

A lithium clinical trial in North America was halted in September 2009. This was not because of safety concerns but because preliminary results did not show the large degree of benefit that the trial specifically set out to demonstrate. Read more about why this trial was stopped and why the UK trial is continuing.

GSK1223249 is a new drug developed by GlaxoSmithKline that targets a protein called Neurite Outgrowth Inhibitor A (Nogo-A). Nogo-A impairs neurone regeneration and is found at higher than normal levels in people with MND. GSK1223249 mops up Nogo-A and may therefore help to limit the loss of connections between motor neurones and muscles.

GlaxoSmithKline has begun a Phase I trial in the UK, France and America, involving around 70 people with MND, in which GSK1223249 will be given to humans for the first time. This study, which aims to recruit approximately 22 patients in the UK at Kings College London and the University of Birmingham, will assess the safety and tolerability of the drug. It is expected to finish in spring 2011.

This new drug, developed by the pharmaceutical company Trophos, has demonstrated in laboratory testing that it is able to enhance motor neurone survival and extend the life of mice that model MND. A Phase 1b trial involving 36 people with ALS demonstrated that the new drug is safe and well tolerated in people with the disease. 

More recently, a Phase II/III, 18 month trial of the drug has enrolled over 450 people with MND at multiple centres across Europe, including Sheffield and King's College London in the UK. This trial will test whether TRO19622 has any beneficial effects in slowing progression of the disease. Recruitment for the trial has now closed and results are expected at the end of 2011.

Visit the Mito Target website for more information on this clinical trial.

Arimoclomol, produced by the biotechnology company CytRx, is a potential treatment that enhances a natural cellular defence mechanism called the heat shock response. This response involves the increased production of protective proteins, known as heat shock proteins, which help cells cope with stress. They help prevent protein aggregation (clumping), which is known to be a feature of MND, and can also help prevent cell death.

A Phase II clinical trial of Arimoclomol has shown that the drug is safe and well tolerated in people with MND. 84 ALS patients in America participated in the double-blind, placebo-controlled trial. Other preliminary data from the study also suggest that Arimoclomol is capable of crossing the blood-brain barrier to reach the central nervous system. On the basis of these results, CytRx will now carry out two further trials to investigate the effectiveness of Arimoclomol. One involves 80 people with SOD1 positive familial ALS in America and is already underway. The other, expected to involve 400 people with sporadic ALS in America and Canada, should get underway in 2010.

A Phase III trial of a drug called Ceftriaxone is ongoing in America. This antibiotic drug, already approved for the treatment of certain infections, was recently found to have additional properties that may be of use in treating MND. Ceftriaxone is able to enter the central nervous system where it can increase levels of a glutamate transporter protein. This helps control levels of the chemical messenger glutamate, which can become too high in the central nervous system of people with MND, leading to motor neurone damage.
Ceftriaxone has already shown promise in animal models of MND and its safety and optimal dose have been established in people with the disease. The current trial involves 600 Americans with MND and is expected to finish in mid-2011.

KNS-760704 is a newly synthesised drug created by Knopp Neuroscience Inc. Although it is not currently known how this drug works in the body, laboratory studies have demonstrated that this drug has neuroprotective properties.
A two-part Phase II trial including 102 people with ALS in America is currently underway. The first part of the trial aims to test the safety and effectiveness of three doses (low, medium and high) of the drug. The second part of the study will then test the safety and effectiveness of the two most tolerated doses. The study is estimated to be complete in 2010.

An excess of the chemical messenger glutamate is thought to contribute to motor neurone degeneration. Memantine suppresses glutamate activity in the central nervous system so it has been suggested that this drug may be helpful in the treatment of MND. Memantine is currently licensed for the treatment of Alzheimer's disease, where abnormal glutamate activity may also play a part.

Canadian researchers at the University of Alberta are currently investigating the effects of memantine on disease progression in 42 people with MND. This phase II trial, which is partly funded by the American ALS Association, is expected to finish in 2010.

In 2007 Phytopharm plc announced the successful completion of a Phase Ib healthy volunteer clinical study for Myogane™, a treatment for Motor Neurone Disease (MND).
Myogane is thought to work by increasing the activity of the body's own neurotrophic factors. It has previously been shown to delay loss of muscle strength and extend survival in an animal model of MND. In this latest study, healthy human volunteers took a liquid form of Myogane, which it is hoped people with MND will find easy to swallow. The study demonstrated that Myogane was safe, well tolerated and easily absorbed.  
Myogane will now need to undergo further clinical testing in people with MND to establish its effectiveness in treating the disease. Phytopharm plc is not yet ready to commence this testing.

Phytopharm announces trial success

Res Inf H - Lessons from Neurotrophic Factor clinical trials (73 kb)

Literally meaning ‘nerve nourishing’, Neurotrophic Factors are small proteins, made by our bodies, which are essential for nerve cell survival and function. The man-made ‘recombinant’ forms of a number of these neurotrophic factor proteins have been investigated in clinical trials for MND. A trial of one of them, Myotrophin (Research Information sheet F - Myotrophin Q&A (87 kb)  (a synthetic form of Insulin Like Growth Factor - IGF1), has recently announced its results.

The Phase II trial involved 330 people with ALS in America and demonstrated that the use of Myotrophin was not beneficial to treat MND. There was a need to conduct this trial as the results of two previous trials (one in North America and one in Europe) on Myotrophin were inconclusive. The objective of the third trial was to determine whether Myotrophin slows the progression of weakness in MND.
Results of European Myotrophin trial (scientific abstract)

Results of USA Myotrophin trial (scientific abstract)

Pioglitazone is an anti-inflammatory drug that is currently prescribed to treat type II diabetes. In the laboratory, Pioglitazone has demonstrated that it can reduce the inflammation of neurones, which could be beneficial in MND.
An 18 month Phase II trial recently began enrolling participants, it will involve up to 220 people with MND in Germany and Italy to test the effectiveness, safety and tolerability of Pioglitazone. This trial is expected to be completed in 2010.

Pioglitazone is also being trialled in America in combination with another potentially neuroprotective drug called Tretinoin, as it has been suggested that a cocktail of drugs may provide the best chance of tackling a complex disease like MND. The safety and efficacy of the combination is being tested in 30 people with MND.

SB-509 is a newly synthesised gene therapy drug created by Sagamo Biosciences. This drug works by increasing the level of the neurotrophic factor VEGF. An 18 month Phase II clinical trial designed to test the safety and efficacy of SB-509 is currently recruiting participants and will involve 40 people with ALS in America. This trial is expected to be complete in 2010.

sNN0029 is a drug sponsored by the pharmaceutical company NeuroNova and contains the "nerve nourishing" neurotrophic factor VEGF.
In MND animal model studies, direct administration of VEGF into the fluid filled cavity of the brain via a catheter and pump improved the animals’ muscle strength and prolonged survival.
A three-month, two-phased trial (Phase I and Phase II) will soon begin enrolling participants to test the safety and tolerability of this drug in people with ALS. The trial will be conducted in one centre in Belgium and will enrol up to 28 people with ALS. It is estimated that this trial will be complete in late-2010.

More informaiton on the sNN0029 trial (clinicaltrials.gov website)

Talampanel is a drug synthesised by Teva Pharmaceutical Industries. In the laboratory this drug has demonstrated that it can block a chemical signal called glutamate, that is too high in people with MND, from signalling which may stop motor neurone damage. An 18 month Phase II trial is currently recruiting participants in North America and Europe, excluding the UK. The trial will involve up to 540 people with MND and will be testing the safety, tolerability and effectiveness of the drug. The trial is estimated to be complete in 2010.

Thalidomide is a drug with a tarnished reputation, having caused birth defects when given to pregnant women in the 1960s. However, aside from its adverse effects on pregnancies, it might still be useful - it is an anti-inflammatory drug, which may be capable of suppressing some of the inflammatory factors that are seen at raised levels in people with MND.

Two phase II studies in Germany and the USA recently investigated the safety and effectiveness of thalidomide in MND patients. Unfortunately, the German trial had to be terminated early when some of the participants developed heart problems that were attributed to the thalidomide – this outcome may limit future testing of the drug in MND and other neurological diseases. The American trial was completed but the results are still outstanding.

Results of German Thalidomide Clinical Trial (scientific abstract)

TUDCA is a substance derived from bile acid that has demonstrated antioxidant and neuroprotective properties in the laboratory. A small Phase II trial in Italy involving 20 people with MND is now underway to assess whether the addition of TUDCA to riluzole can slow the progression of the disease. The trial will run for 12 months and results are expected in early 2011.