AZD1236 Investigational Drug Fosters Nerve Repair After Spinal Injury

[goldnucs]

https://www.disabled-world.com/disab...al/azd1390.php

[skippopotamus]

More info about azd1236
https://youtu.be/Nuv8b6VmJoU

[lunasicc42]

"The announcement comes weeks after the same research team showed a different investigational drug (AZD1236) could reduce damage after spinal cord injury by blocking the inflammatory response"

So, in other words; a potential treatment for Acute injuries

[skippopotamus]

I also think its for acutes Luna. I'm not finding a lot of data on it which is strange because it is well tested in humans for pulmonary disease and some of the testing is ten years old.

https://clinicaltrials.gov/ct2/resul...e=&city=&dist=

[lunasicc42]

I used to be in that same boat with all the people saying: "acute research and trials will eventually help us chronics too" but now I am pretty anti that ...it's almost a whole different injury....Acute vs chronic I mean

[skippopotamus]

I’m not great at interpreting the results from the trials so possibly the pulmonary trial results were not good enough to move forward as a treatment for that.
Maybe I’m not finding SCI data because it’s in the UK, Denmark, Finland etc or it’s a red herring and there’s nothing there.

[skippopotamus]

With a little hunting and some fumbling around I was able to find data.
“In conclusion, we showed that AZD1236, administered within 24 h after SCI and for only 3 days, promotes unequivocal positive benefits to the key pathophysiological consequences of SCI.^6-10 AZD1236 suppresses SCI-induced oedema, BSCB breakdown, neuropathic pain, scarring and infiltration of macrophages into the lesion site while at the same time promoting axon regeneration, leading to improvements in electrophysiological, sensory and locomotor function.”

So it is for acutes which is a bummer but I would be ok with no new members in the SCI club.

Here is the article in case some desperate newly injured person is looking for it.
https://onlinelibrary.wiley.com/shar....1002/ctm2.884

[ActionXPotential]

This is actually incredibly interesting to me. The drug acts on a class of proteins called matrix metalloproteases (MMP). These essentially break down and digest proteins existing outside of the cell, similar to the actions of Chondroitinase ABC. However, while Chondroitinase ABC is specific to the inhibitory chondroitin sulfate proteoglycans (CSPGs), matrix metalloproteases digest everything, including proteins needed to maintain a healthy environment. Typically the actions of these MMPs are believed to promote inflammation, lead to death of neurons, and dieback of axons (regenerative failure). This drug looks like it blocks two key MMPs, specifically, MMP 9 and 12, which could have therapeutic properties for ACUTE SCI as far as we know. In fact, the literature dates back a long ways talking about the role of MMP9 in spinal cord injury so there isnt really that much new with regards to intervening to block MMP9. The better question is why has it taken so long to consider it for clinical use....

What I will say, I am currently running some chronic SCI experiments in rodents to better understand the chronically injured spinal cord and found, to my surprise, that MMP12 is one of the highest upregulated proteins in chronic SCI (percentage relative to an uninjured cord). This protein has no business being there. These proteins can be affiliated with pain, regenerative failure, etc. So, while im sure the intent of this line of work is to treat acute SCI to be neuroprotective, there is still some role of MMPs, particularly MMP12 in chronic SCI and we have no idea what exactly it is doing. I have been looking for an MMP12 inhibitor to test the role of MMP12 on regenerative failure in chronic SCI so this is exciting for me to read. At the very least this could be a tool to see if MMP12 is causing any problems in the chronically injured cord.

[skippopotamus]

"The better question is why has it taken so long to consider it for clinical use...." -ActionXPotential

I really, really thought about and struggled with what could be holding this up. New people are joining the SCI Club every day.

I asked Professor Ahmed what was holding back a Phase 2 trial of AZD1236 and he responded! He said that with only around 2500 people getting spinal cord injuries UK funders are very difficult to persuade and pharma are reluctant because their profits will be too low. But he has found a venture capitalist partner to bring AZD1236 into clinical trials with Astra Zeneca's help.

So there is progress but it is very slow and it is not due to Astra Zeneca as they are not interested in SCI.