Treatments Trials

A number of trials funded by pharmaceutical companies 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 Association provides information on specific drug trials and liaises with drug companies 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. 

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.

Astrocytes are specialised cells that support neurones in the brain and spine. Recent laboratory evidence has suggested that in MND, astrocytes become over-stimulated, upsetting the delicate balance of chemicals in the central nervous system and contributing to the degeneration of motor neurones.

ONO-2506PO, a drug developed by Ono Pharmaceuticals, acts on astroctyes to suppress over-stimulation. Laboratory testing has shown that the drug may help to stop the degeneration of motor neurones. An 18-month clinical trial designed to test the long term safety and efficacy of ONO-250PO in treating ALS is now underway across Europe. Two centres in the UK (Preston and Sheffield) are participating in the trial, but are no longer recruiting people with MND to take part.

Laboratory studies on animal models of MND found that Glatiramer Acetate (also known as Copaxone), licenced for the treatment of Multiple Sclerosis, was shown to extend survival. These mice received a single, under the skin (sub-cutaneus, s.c.) vaccination at the time of symptom onset, followed by daily oral administration.

Preliminary clinical trials in USA showed that both daily and twice-weekly doses of Glatiramer Acetate over a period of six months were safe and well tolerated by people with MND. However, a subsequent multi-centre European trial designed to test the drug's effectiveness found that Glatiramer Acetate did not slow disease progression or extend survival.

Read more about the laboratory studies and  early clinical trials of Glatiramer Acetate.

Disappointing results from an American Phase III trial of minocycline were announced in May 2007. The aim of the study, which involved over 400 participants, was to determine whether minocycline slowed disease progression and helped maintain muscle function in people with ALS. Unfortunately, minocycline demonstrated no beneficial effect and for some patients worsened measurable outcomes. A previous Phase II trial had indicated that the drug, which belongs to the tetracycline group of antibiotics, was safe and well tolerated. 

It is not yet known what impact these disappointing results will have on plans for a European clinical trial of minocycline.  

Minocycline has previously been shown to delay onset and prolong survival in animal models of MND. In 2002 the eminent scientific journal Nature published further research on the effects of minocycline in an animal model of MND, in which scientists reported that they had discovered the exact biochemical 'target' or site of action for the drug. This discovery could still assist researchers in the development of potential therapies in MND.

Results of Phase III minocycline trial in USA announced

Results of Phase II clinical trial (scientific abstract)

Effects of minocycline in ALS mice (scientific abstract)

In laboratory studies, the drug lithium carbonate 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. 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. Read more about the Italian trial.

A much larger clinical trial, involving around 250 people with MND in North America, will start enrolling participants in summer 2008. European neurologists are also in the early stages of planning a large trial of lithium, which may involve some UK centres. This page will be updated with further details as soon as we have them.

Phytopharm plc has 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)

Arimoclomol 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.

The biotechnology company CytRx has recently completed a Phase II clinical trial of Arimoclomol that 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 prelimary 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, the drug will now progress to the next stage of clinical testing, which is expected to start enrolling American patients in spring 2008.

This American trial assessed the effects of the nutritional supplement creatine (see Res Inf J - Creatine (91 kb) ) in combination with either celecoxib or minocycline. Celecoxib and minocycline are drugs that have shown promise in animal models of MND. The combinations of creatine and celecoxib or creatine and minocycline may be able to impact upon multiple mechanisms of motor neurone damage and have already demonstrated positive effects in the mouse model of MND.
The trial used a new trial design in order to establish that the creatine & celecoxib combination was superior. The results were presented at the 18th International Symposium on ALS/MND.

A phase III trial of a drug called Ceftriaxone has begun enrolling patients in the USA. 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 will involve up to 600 Americans with MND and is expected to finish in mid-2009.

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. More recently, a Phase 1b trial involving 36 people with ALS demonstrated that the new drug is safe and well tolerated in people with the disease. Those participating in the trial were taking riluzole alongside TRO19622. The results of this trial were presented at the 18th International Symposium on ALS/MND.

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 efficacy 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.

The results are pending in a clinical trial in New York investigating the effects this antioxidant in MND. The effects of co-enzyme Q10 are being monitored by imaging studies of the brain during the trial. This is the second study following the encouraging results in a very small, preliminary trial in the same institute.

A previous trial found that Co-Q10 was safe and well tolerated when taken for a nine-month period.

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 taken place in America.

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. The study was a two year placebo-controlled trial involving 330 patients in 16 centres around North America. The last participants finished the trial in December 2007 and the results should be available later in 2008.

Results of European Myotrophin trial (scientific abstract)

Results of USA Myotrophin trial (scientific abstract)

One possible cause of motor neurone damage in MND is the action of toxic waste products within cells. Vitamin E is an antioxidant that protects cells against these effects (Res Inf K- Antioxidants (81 kb) ). The results of two studies on the use of Vitamin E in MND have shown that at doses of 1,000mg per day and 5,000mg per day it did not alter survival time in people with MND. The trial of the lower dose of the supplement showed that it may help alleviate the symptoms of MND. Researchers in Canada are now recruiting people with MND for a trial to see if vitamin E can reduce the frequency and severity of muscle cramps.

Results of lower dose clinical trial (scientific abstract)

Results of higher dose clinical trial (scientific abstract)