Recently, Brainstorm Cell Therapeutics published a paper in the Journal of the American Medical Association (JAMA) Neurology. The paper recaps two different clinical trials done by the company on their NurOwn® platform. Below is brief overview of the paper’s general findings. For a discussion among people with ALS and their families about these findings, visit the ALS Forum

What did the paper say?

This paper reports on the findings from 2 previous clinical trials operated by Brainstorm Cell Therapeutics (“Brainstorm”) over the past several years. Those trials occurred in Israel between 2011 and 2014. Neither trial was designed to measure efficacy. Both trials resulted in the same finding – the treatment was found to be safe and tolerable in people with ALS. The authors state, and the ALS Therapy Development Institute agrees, that additional trials are required to determine any potential efficacy of this treatment in ALS.

Brainstorm harvests mesenchymal stem cells (MSC) from individuals with ALS and then modifies those cells using a proprietary technique in hopes of enhancing those cells’ ability to secrete neurotrophic factors (NFT), which are proteins that neurons require for health and survival. According to the paper, all the cells harvested were modified and confirmed to express higher amounts of glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF)  and hepatocyte growth factor (HGF) before they were reinserted into an individual’s spinal cord or muscle. It is important to note that, as should be expected, not all cells modified from all participants were found to express the same amount of these neuro-nutrients, nor is it entirely understood whether one specific neurotrophic factor is more important to combat or needed by each individual persons central nervous system in the study in order to combat ALS.

A total of 26 people with ALS participated in these two clinical trials. In the first trial - a Phase 1/2 clinical trial - 12 people with ALS participated and received a single treatment of modified mesenchymal stem cells directly to their spinal cord (intrathecally) or through a series of injections to their biceps and triceps (intramuscularly). In the later Phase 2a clinical trial, 14 people with ALS received a single treatment both intrathecally and intramuscularly but at three various dose levels. Four people with ALS in that trial received the low dose of cells, 6 people received a middle dose and 4 people the highest dose in the trial. In both trials, all enrolled participants remained in the hospital for 72 hours following treatment to determine potential side effects. No severe adverse events were associated with treatment and most common side effects reported overall in the trial were headaches, fever and pain in the extremities.

The paper discusses the secondary endpoint of ALSFRS-R and FVC measurements, which are two commonly accepted measurements of disease progression. However, the study size here is very small and not powered sufficiently to measure an effect on disase progression. As the authors of the paper note, additional clincial research should, and is being done, to understand any potential impact on disease progression, otherwise known as efficacy.

What does this mean?

This paper reports the outcomes from earlier studies done using the Brainstorm product. These results have been discussed in various ways previously at a number of science conferences. These were early stage clinical trials. And, much of the data presented in the paper has been presented, discussed or hinted at during science conferences before and reported on in part through our meeting reports from those conferences when available. The results shouldn’t be over interpreted beyond the conclusions - that the treatment was found to be safe and tolerated and that clinical benefits need to be understood in future trials as the authors state.

Based on this publication, and according to its authors, the treatment used by Brainstorm in this trial was proven to be safe in people with ALS, but it is not yet proven to be an effective treatment for ALS. Additional trials are underway to advance the understanding of whether or not that is the case.

There is another trial being conducted by this company on many more people with ALS, and we will wait to see those results, which are slated for sometime in 2016. It is likely that a peek at those results will be available at science conferences later this year, given that it is already fully enrolled. We will report on those public findings. The ALS Therapy Development Institute pointed many people with ALS to Brainstorm’s clinical trials over the years and held a webinar with a member of their senior medical affairs team as well.

Are we excited?

Anytime that a trial in ALS has positive results, no matter how early in the clinical development process, we get excited. Because this trial is still in early stages of the clinical trial process, we are watching its developments and look forward to seeing the results from the larger Phase 2 clinical trial which recently completed enrollment in the United States and will open soon in Israel.

We need a treatment for ALS already, and this is one of many in the works. There are later stage clinical trials including Cytokinetics’ tirasemtiv which is in Phase 3 here in the US for example. For a full list of currently enrolling clinical trials worldwide, please visit our clinical trial database.

Helpful Links:

-    Brainstorm Press Release

-    JAMA Neurology Paper

-    Webinar with Brainstorm

-    Clinical Trial Database