DRACO rides again?

A decade ago a scientist named Dr. Todd Rider had a clever idea for an anti-viral drug.  In normal eukaryotic cells you have DNA that spends most of its time as a double strand except when being copied or transcribed to an RNA message.  That RNA message is single stranded as is the rest of the RNA in your cells except for the occasional short length in some cell processes.  But generally a big length of double stranded RNA in a cell means that a cell was infected with a virus.  Either a virus that naturally transmits itself with double stranded RNA or one engaged in copying itself within a cell.  DNA viruses generally don't make this and some RNA viruses such as AIDS use DNA to copy themselves but most viruses we worry about involve double stranded RNA.  And DR. Rider's drug uses this as its point of attack.

Now, evolution is quite aware that double stranded RNA is bad news and your innate immune system already has weapons against it.  We all have barriers like skin and mucus to keep unwanted stuff out of our bodies.  We also have our adaptive immune systems that notice infections and develop weapons against a specific pathogen like antibodies.  But we also have our innate immune system which is a big collection of tricks our bodies have to recognize common patterns pathogens exhibit and fight back.  Some of these already target double stranded RNA like Dicer, an enzyme that cuts up double stranded RNA it finds in a way that tends to jam up other copies of the same RNA.  But our cells have a large number of strategies such as attacking viruses and viral replication directly, noticing that they are infected and killing themselves (thanks mitochondria), or signaling that something is wrong via signals like cytokines.  But any virus that can successfully attack you will have a range of strategies for avoiding the particular innate immune system of the creatures it targets, which is part of what makes viruses species specific along with things like needing to have a way into target cells.

Dr. Rider's drug, DRACO or Double-stranded RNA Activated Caspase Oligomerizer, essentially adds a new element to your body's innate immune system instructing cells to kill themselves by a new method which viruses won't have any way of evading.  Now, just having a mechanism of action isn't good enough. You also need a way of getting it into the body.  And bodies are very complex so you need to make sure that there aren't accidental side effects and that it can actually work in practice.  But Dr. Rider was able to show success against a fair number of viruses in mice and another group was able to replicate that success in pigs.

So why aren't we all taking DRACO whenever we get the flu now?  Well, somehow they were never able to get enough money for continued development.  There was even a crowdfunding campaign I contributed to that didn't raise nearly enough.  Why didn't the NIH fund them?  Well the NIH works by committee and this drug has a weird mechanism of action so it's not surprising that they didn't get money there.  Why not private money?  Well I wasn't able to track down the source from a decade ago but after the failed crowdfunding I heard that Dr. Rider was hoping to emulate Dr. Howard Florey, one of the key contributors to penicillin, who refused to make any money from his invention but just wanted it to benefit mankind.  That sort of thing worked fine in the 1930s when you could just inject a drug into a few people with life threatening infections, watch their recoveries, and then have everybody use your drug.  But these days that route to FDA approval for a drug is much more laborious and complex and requires drastically more money than the NIH can hand out, let alone crowdfunding.  You need venture capitalists with very deep pockets who see a way to get a return on their investment.  So hearing that I sort of gave up on the project.

But there's more than one way to skin a cat.  Even if DRACO itself is unpatentable and so unable to do the work to receive the blessings of the medical establishment you can still create a distinct drug that works on similar principles.  Heck, Scott Alexander wrote about how some company managed to create their own version of fish oil that they shepherded through FDA trials.  And even though it might not be better than regular fish oil and even though it costs ten times as much FDA approval lets hospitals stock it and lets insurance pay for it, unlike regular fish oil.

And this process of creating a new, patentable version of a drug seems like it might rescue DRACO.  There's now a group, Kimer Med working out of New Zealand, had created their own drug similar to DRACO and were working on bringing it to market in a much more conventional way than DRACO attempted.  They were apparently able to raise $14 million in their first funding round and are looking at a second so they've already raised more than an order of magnitude more than Dr. Rider was hoping to.  And I very much wish them success because our wonderful connected global civilization won't be sustainable in the presence of continued zoonotic crossovers unless we can keep improving our treatment of infectious disease.