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-1, CNTF 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.