Thread by @seanchaibeag

(#COVID19 and orphan drugs thread: 1/9)

My original life plan from ~8 was to be a pulmonologist specializing in cystic fibrosis. I spent all my free time at uni on an underground citizen research team dedicated to trying to crack the biochemistry.

israel21c.org/dont-invent-ne…

(2/9) We were on the right track, but ~20 years too early; our research was the very very VERY beginnings of what eventually led to ivacaftor (Kalydeco). So when I plow through a Covid abstract & break it down a bit, know that I have no qualifications, but it’s a lifelong hobby.

(3/9) The piece above reminds me of a solo trip to the local science museum during a history of medicine exhibit. A substantial section was devoted to “orphan drugs” – drugs that had been fully developed and passed safety testing, but never got funded for efficacy trials/license.

(4/9) One of them was dornase alfa. I kept circling back to it. Wrote it down. Couldn’t get it out of my head. This was ~1990, so research=library... & I did. Photocopied the little I found. Sat in my bedroom, staring at it. Dornase alfa likes to chew on a particular kind of DNA.

(5/9) Specifically, it likes polymerized DNA. VERY simplified, infection causes release of neutrophils, and when the neutrophils die, you get polymerized DNA. The upshot is, infection/inflammation + thick secretions? Dornase alfa wants to thin that mucus out for you.

(6/9) That’s why I kept staring at my photocopies. How was this an abandoned drug? Surely this was a mucolytic? Useful for CF, maybe selective other infection scenarios... right? Wouldn’t work as a *pill* (the form I saw it in) but aerosolize it! Gentlemen start your nebulizers!

(7/9) I kept waiting for it to be announced on the news. I was just a *kid*... surely if I’d spotted this, someone else had. There’s a drug just sitting in a damn display case in Atlanta that could help millions. Maybe I was wrong... maybe it couldn’t be synthesized as a liquid?

(8/9) In 1992, dornase alfa was approved by the FDA for the treatment of CF. You know it as Pulmozyme. Dornase alfa has recently been studied vis-à-vis Covid pneumonia. It works there too. But because neb treatments are an aerosolizing procedure, it’s not being administered.

(9/9) Something to ponder, especially now hospitals are forced to triage more strictly. If I were sent home w/ Covid pneumonia, I’d be asking my doc about Pulmozyme (& if deemed appropriate, nebulizing it outside, where the aerosolization wouldn’t endanger anyone I live with).

COVID-19 and dornase alfa abstract link: ncbi.nlm.nih.gov/pmc/articles/P…