[Siok Tan]

Amanda, I agree that ALS research should incorporate more genetic testing to identify the culprit genes that cause the disease. By looking at types of gene mutations and correlating it to a patient’s symptoms could potentially “personalize” the way patients are treated, increasing success. This approach has been done rather successfully in certain types of cancer. For instance, if a certain culprit mutation is found to cause disease, then you can use drugs that target that mutation to treat the disease. If it is a single gene mutation, there is also possibility of gene therapy. Next Generation Sequencing (NGS) technologies have definitely revolutionized the way medicine is practiced, and have allowed us to interrogate the DNA quicker and much cheaper, compared to conventional methods and in turn allowing faster rate of discovery at a cheaper rate. I have not done any extensive research to find out how much extensive NGS work has been done on ALS, but it will be interesting to find out.

The other potential direction is to also use NGS to find out the mechanisms for disease reversal, which has happened to some ALS individuals. If we can pinpoint what enables them to reverse the disease, then that could be a potential treatment route.

[Siok Tan]

The announcement from Brainstorm is certainly very disappointing. My husband has ALS for 6 years, and we were so hopeful for positive results from the trial. Looking at what little results/data were announced, it looks like the trial did succeed in treating the patients in the treatment group. If we only look at the data from the treatment group, the expected treatment response rate of 35% was attained showing that the treatment works! The issue lies with the data from the placebo group who did better than expected. Many reasons could have resulted in this. Firstly, patients who participate in trials somehow have a tendency to assume they are on the treatment group. I am a clinical scientist who runs clinical trials (not ALS trials), and there had been many instances when our patients “believe” that they have the treatment, only to discover that they are on the placebo group (we did a survey with our patients and were able to show that patients tend to think they are on the treatment group). With the ongoing hype about how NurOwn is able to reverse the disease, the placebo patients who believe they are on the treatment group will “think” they are feeling better. The next issue lies with the fact on how their progression are measured. Both primary and secondary endpoints in this trial rely on this one questionnaire ALSFRS, which can be rather subjective. There is currently no objective way to measure ALS progression (unlike some other diseases where you can do scans to objectively see how the disease has progressed). However, one way that allow us to look at the data objectively is to look at the biomarkers measured in the trial, which according to Brainstorm, shows “statistically significant increase in the levels of neurotrophic factors and reduction in neurodegenerative and neuroinflammatory biomarkers that was not observed in the placebo treatment group”. This means biologically, things are going the way it should be in the body! The last thing we need to remind ourselves is the fact that for some patients, final follow-up visits were done remotely due to COVID-19 pandemic. I don’t know if this will affect the data, but if the person administering the questionnaire is unable to physically see the patient, will that allow the patient to provide inaccurate data without the research coordinator being there to “judge” if this was true? One interesting thing that can be done is to ask the patients if they thought they were in the treatment or placebo group, before they are unblinded.

I am sorry this is such a long message, but I wanted to bring some points across. Please don’t lose heart, as NurOwn is still a possibility. My question is, how and when. Does anyone know if any actions were taken to persuade FDA to take actions ASAP? I know there is a bill that needs to be passed to allow ALS patients access to experimental drugs, but other than that I have not heard of any petition or actions. Does anyone have additional information that they can share? Thanks.