It was announced, via press release, that a compound being pursued by Genervon Biopharmaceuticals LLC may have been effective in improving the ability of one person with ALS to speak and swallow.  It is paramount to note that this report is from a single patient, who was exposed to the drug GM6 though a compassionate use patient trial.   Further, this data alone is unlikely to be sufficient evidence for FDA approval of GM604 (aka GM6) as an effective therapy for ALS. Further analysis of GM6 is highly likely to occur both in and out of clinical trial settings.

The PALS participating in the compassionate use trial is male and was diagnosed with ALS nearly 10 years ago. According to Genervon, he has been a quadriplegic and on a ventilator since 2008. The purpose of this study was to gather data from later stage ALS patients and compare it to data from a phase 2 trial done in early stage ALS patients. The company conducted a number of tests on patients’ cerebrospinal fluid (CSF) to attempt to determine if their compound had any measurable effect on proposed biomarkers of ALS thought to be found in CSF, including SOD1, Cystatin C, and tau.

Earlier clinical trials of Genervon include a Phase 1 in healthy volunteers and a Phase 2 trial on 12 people with ALS.  The double blind placebo controlled trial was conducted over a period of 12 weeks with PALS receiving the drug (or placebo) intravenously during the first two weeks only, with follow up visits after that. CSF samples were collected before being given drug (baseline), at completion of treatment program (week 2), and at the end of the observational period (week 12). This trial’s main objective was to measure changes in biomarkers found within CSF overtime and to determine if GM6 was safe and tolerated well by PALS.  Results from this study have not yet been published by Genervon, however it put out a press release in October 2014 claiming that they saw a “statistically significant” effect on both clinical and biomarker data in both ALS and PD clinical trials. 

It is the opinion of ALSTDI that this trial was too small and too short to statistically measure an effect on disease progression.  However, we believe that Genervon should continue its effort with their compound, including the organization and execution of additional clinical trials.

What is GM6?

Described as an “endogenous signaling master regulator,” GM6 seems to be a unique compound created to regulate a specific aspect of cell health, specifically motor neurons. There are many things which motor neurons require to be healthy and part of a vibrant system, including a well-regulated abundance of different proteins called neurotrophins or neurotrophin factors. These include brain-derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), and mononeurotrophic factor (MNTF) among others.  GM6 is proposed as a regulator of MNTF.  MNTF is believed to play a role in nearly every aspect of motor neuron development; including initial differentiation, maintenance, survival, axonal growth, and inervation of axons into muscles. Genervon believes that GM6 regulates, directly or in part, the expression of more than 4000 genes in the body, including some which are involved in ALS biology.

Helpful Links:

About GM6: http://www.als.net/ALS-Research/116/ALS-Topics/

The Institute's Statement on Phase 2a Clinical Trial: http://www.als.net/Media/5470/News/

FDA's Statement to Genervon on GM6: http://www.fda.gov/Drugs/DrugSafety/ucm443242.htm 

Genervon Press Releases: http://www.genervon.com/genervon/about_pressreleases.php 

ALS Forum Thread: http://www.als.net/forum/yaf_postsm396374_Genervon-Announces-Phase-2a-Trial-Results.aspx