Understanding more about GM604

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The MND Association’s Director of Research, Brian Dickie explains more about ‘GM6’, also known as ‘GM604’, a drug in development by an American pharmaceutical company Genervon.

The Association funds a wide range of research that leads to new understanding and treatments, which may one day, bring us closer to a cure for MND. We are hopeful that the increasing international research effort into the disease will accelerate the development of an effective treatment for MND. However for non scientists I also fully appreciate how the ‘system’ often seems designed to impede rather than assist this process.

There has been much discussion online about the results of a small scale study of a drug called GM604, or GM6, produced by the American pharmaceutical company Genervon. You can read some general comments about the drug on our website. I’ve written this blog to explain in a little more detail why the research community is cautious about the results.

What is GM604?

The Genervon molecule GM604 is a small peptide (a peptide is a biological building block) styled as a ‘master regulator’ in embryonic development. As such, there is certainly a rationale for its use (although adult motor neurons are very different from embryonic ones) but it does appear to be a variation on a theme that has been around for many years. From the very limited information available, the peptide appears to be a type of neurotrophic factor. Neurotrophic factors play a crucial role in the development of the nervous system and there have been many studies of their potential as treatments for MND. They are very effective at keeping neurons alive in the dish and in mouse models of neurodegenerative disease, but they have unfortunately not been demonstrably effective in large scale clinical trials in humans (for example, IGF-1CNTF and BDNF ).

At present, we do not know if GM604 will be any different to other neurotrophic factors. As explained in the recent letter posted by the ALS Association on their website small, short-term studies tell us very little beyond the fact that the drug appears to be safe. Genervon has only published their results by press release therefore the full detail is not available for scrutiny by the research community.

Genervon has recently met the Food and Drug Administration (FDA) to discuss the possibility of gaining ‘accelerated approval’ for GM604. (The FDA is the American agency that licences drugs). Like the research community, the FDA will have also required thorough data showing the safety and effectiveness of the drug – something that can only be established through adequate and well-controlled studies. Their meeting took place in February, and the FDA’s decision has not been announced yet.

To learn more about the different types of clinical trial and how they are conducted, please see our clinical trials information sheet .

What we learnt from lithium

Lithium is a recent example of how excitement about the results from a small-scale trial did not bear up to more rigorous scrutiny. In 2008 a clinical trial of lithium was conducted in Italy in 44 patients with MND. It showed a striking reduction in disease progression in those taking lithium compared to the control (placebo) group (Fornai et al 2008). However, in larger phase III clinical trials this beneficial effect of lithium was not observed (in either a North American study or a study conducted in the UK) . In the UK trial over 200 participants took part across several centres. There was no overall effect, but if you looked at the data from each individual centre (which each recruited approximately 20 participants) there was considerable variation: in some centres it looked like lithium was working, but in others it looked like it was having a detrimental effect.

The message from this and other studies is that looking at small numbers in isolation can throw up very misleading results, which is why these preliminary GM604 findings need to be reproduced on a much larger scale for a longer time-period (months not weeks) to establish if there is a genuine beneficial effect and that there are no side effects associated with long-term use of the drug.

The Genervon story also strikes a chord with the initial results of NP001. I would encourage you to read the blog article I wrote at the time, which may help further explain why the ALS/MND clinical and research communities are cautious about the interpretation of small, short-term studies.

So, like everyone else, we will keenly await the FDA decision regarding this potential treatment, and what Genervon’s next steps will be.

8 thoughts on “Understanding more about GM604

    1. Dear Paul,

      Thank you for your blog comment. GM604 is currently an unproven treatment for MND as it has not passed the appropriate clinical trial testing to prove it is safe and beneficial in MND. You can find out more about unproven treatment here.

      This blog post and the link above explains the current situation regarding GM604 and it will be up to the FDA to decide what the next steps will be. You can contact us on, where we will be happy to discuss anything further.

      Kind regards,
      Research development team
      MND Association, UK

  1. Thanks for at least commenting on the potential for GM604. Sometimes it seems like the research community lack any sense of urgency when our loved ones are slipping away in such a cruel way we just want even a faint ray of hope.

  2. I think that it is relatively easy to see why we should be skeptical about a study of 12 patients that has a p-value of 0.03 as in this study. First you must understand that hundreds of ALS drugs are tested around the world. Optimistically maybe one out of 20 of these might be worthwhile. More importantly the chance of 12 patient study showing that a worthwhile study is worthwhile, the so called “power”, is only 15% or so. Thus simple math can show how certain we should be that a drug like GM6 is effective. Suppose we test a thousand drugs, with very small studies and 50 of these drugs are really effective. Then roughly 9 of these will be found because with these studies have a power of 15%. Now of the 1000 drugs an additional 14 would be found at a 3% sigificance level that aren’t effective. So the chance of GM6 being effective is roughly 9/(23) 40%. This makes the optimistic assumption that 5% of the drugs we test are worthwhile.

    The company that owns GM6 Genevans, could do a larger confirmatory trial very quickly. ALS trials accrue quickly. Furthermore the design could be such that patients who show the first signs of progression could be treated with GM6. We would really know whether or not the drug worked in a year. I think it is a disservice to ALS patients to put a possibly ineffective drug on the market without really showing that it is effective.

  3. Thanks for the informative article. It was worth reading. We gain good knowledge about GM604 from this post.

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