So, I try not to get technical and use this as my venting post but I’m particularly excited right now. So as some of you know I’m SOD1 FALS which is good and bad all wrapped into one. It’s good because I’m the most popular kid in the class. I was the first jacked up ALS gene discovered, I’m the basis of most research in SOD1 mice, and most of the gene therapy and ASO’s right now are aimed at SOD1. Basically, I have hope that if anyone is going to get figured out its going to be my cool group of PALS. The bad side is that I have ALS haha.
So, I’ve been in a trial and while I have no idea if I am getting the drugs I have felt better this month. Basically, the trial was screened through CRP (C-reactive Protein) which is now being touted as an ALS biomarker. CRP is essentially a protein that is released into the bloodstream to fight an illness or inflammation. Inflammation sounds fun, doesn’t it? So, I’m going to discuss a few drugs but not say what trial I am in and where I see the pipeline going. Many have the theory that ALS will eventually be treated through a cocktail of drugs just like HIV. Not everyone with ALS has the same cause, same reactions, or same gene abnormalities so it’s going to be confusing to figure out.
A few months ago, Edavarone was approved by the FDA as the first drug to “treat” ALS in 22 years. Personally, I think the drug makes a lot of claims and doesn’t have a lot of back up. It was never trialed in the US and was used in Japan. It’s an antioxidant free radical scavenger. The point is for it to attempt to scrap our unpaired, unstable, and deadly molecules. Free radicals basically cause cell death. So Edavarone doesn’t “fix” the problem. I compare it to dropping a bottle of red wine on white carpet but trying to blot it with a single paper towel. It’s going to clean up some wine but your carpet still looks like crap.
Now there are something like 64 other drugs in trial stages for ALS. I’m particularly excited about a few of them. One of them is Biogen and ISIS’s SOD1 ASO. An ASO is an Antisense Oligonucleotide. Big words that mean the reduction of the production of superoxide dismutase 1 (SOD1). OH, THAT’S ME! So, a few things get me pumped up about this. Numero Uno being that Biogen is a legit worldwide pharma power. There aren’t enough big pharma companies pushing ALS drugs and quite frankly they don’t mess around. I’ve done work on the building side with Biogen and nothing moves slow and nothing stands in their way. We’ve built filler lines in three months so it won’t be “Waiting years for production”. Number two is that this is a phase 1 / 2 trial. They are pushing on this hard. Phase 1 evaluates safety and phase 2 to is to evaluate effectiveness. So, this drug could possibly be pushed right into phase 3 afterwards and into a NDA (new drug application). I just honestly don’t believe they would be perusing it this hard if it didn’t merit excitement. So now the cause is being addressed.
Another trial is NP001 which is an anti -inflammatory which most believe is based on sodium chlorite. The drug failed to meet phase 2 goals but they found something promising. Out of the small percentage of people that either improved in condition or stabilized without further progression all people had elevated CRP. This is a twofold win for me. For one I hate the trial process for ALS. We are all different and all trials lump everyone together (except for gene trials). Now a drug has specifically addressed a subset of ALS patients which is obvious yet brilliant and innovative. So, I think this could be used in conjunction with other drugs adding another step to the cocktail.
My only odd feeling about NP001 is that in my opinion Edavarone would need to be strategically combined. From what I’ve gathered NP001 does not play well with antioxidants and reduces the effectiveness. None of this is official but assumes that NP001 is sodium chlorite based. Could be completely wrong there but it could also possibly be staggered. Edavarone is meant to be a lifetime drug of a rotation consisting of 10 days of infusions and 10 days off. I’m not sure how they would play together in the pool but who knows. If nothing else there is going to be another process required to figure that out.
Lastly is masitinib. This drug is a repurposed drug used by vets to treat cancer in dogs. Say what? The drug has a target is to reduce inflammation and it is a kinase inhibitor. I would be shocked if this wasn’t FDA approved by the end of year. There have been numerous questions involving AB and the clinical protocols but to me the backup seems more substantial than what was provided with edavarone. Also, not sure who and how is treated by masitinib. For instance, NP001 was found to work effectively only in people with elevated CRP levels. This is where I get a bit lost and need to research a bit. I’m not sure if the goal is to reduce the inflammatory response itself or to remove the proteins that may be misfolded due to the accumulation. Kind of a chicken or the egg deal. Now a kinase inhibitor such as masitinib are enzymes that group to a protein and change the function. The reason that the drug was previously marketed as a cancer treatment is it inhibits overexpressed kinases in cancer. I also know that many trials are opening up participants to taking edavarone now. Will be interesting to see if the new masitinib or NP001 trial include that option.
The idea of an inhibitor and drug to reduce the inflammation itself would seem to be a double whammy combined. Now the kicker is that a large percentage of PALS DO NOT have elevated CRP levels but do have elevated CPK levels. So, in theory the combination of NP001 and masitinib would really only be beneficial to those having a high CRP level. The high CPK level maybe a biomarker for masitinib which is common amongst most PALS. Again, this is a possible cocktail with riluzole also for some. Both drugs were trialed with the inclusion of those taking riluzole. I do worry that NP001 has been around for 5 years and hasn’t made it to phase 3 but do feel there are too many miracle stories to ignore it.
So basically, if you throw all those kids into the pool you have addressed the source for SOD1, a kinase inhibitor, a possible free radical scavenger, a glutamate regulator, and an anti-inflammatory. Wow! I’ve stayed cautiously hopeful about ALS treatments but all of this is extremely exciting.
If none of this made sense or no one cares I get it but it gives me chills. For the last 22 years we’ve had one halfcocked drug to “treat” ALS which offered a possible 10% extension of life. Now we are using figures like 25-30% on each drug. It’s obviously not a “add them all up” situation but it’s becoming clear that life is and will be extended shortly.