from the the-internet-to-the-rescue dept

Doctor With Rare Disease Crowdsourced His Own Cure, And Is Now Using That Network To Work On COVID-19

A recent episode of NPR's Fresh Air ran an amazing interview with Dr. David Fajgenbaum, who was diagnosed years ago with the rare Castleman's Disease, about which very little information was known (and the general prognosis was grim). Fajgenbaum talks about how he ended up in hospitals believing that he was about to die five separate times (he even had his last rites read to him), but then set up his own organization to try to crowdsource a cure. He details the full story in his book that was published last fall, called Chasing My Cure.

The good news is through that crowdsourcing effort, called the Castleman Disease Collaborative Network (CDCN), they at least found a treatment that (for now...) appears to work for Fajgenbaum himself:

The biggest difference between this fifth time I nearly died and the previous four times is that, at this stage, I was engaged. And I had the ultimate date in mind, which is our wedding date, May 24, 2014 - in mind as the driver to say, I need to find something. I failed to respond to all these drugs. There's nothing left for me. But I have to make it to May 24, 2014. And so thankfully, this combination of seven chemotherapies saved my life.

And when I got out of the hospital, I was able to go back to all those samples I'd been storing on myself and performed a series of experiments where, from within my experiments, I found this pattern that suggested this one communication line in the immune system called the mTOR pathway was highly activated. And what was so exciting about finding this communication line turned on is that there is a drug that was developed 30 years ago that's really good at turning it off. It's called sirolimus.

And just knowing that this pathway was on did not guarantee that blocking it would work and that taking this drug would save my life. In fact, the immune system is a very finicky system. And basically, turning off this communication line could have actually caused even more problems. No one knew because this drug had never been given to a Castleman disease patient before.

But really, knowing that I needed to try something if I wanted to make it to our wedding date, I decided to take the leap of faith and to start taking this drug as the first patient with my disease ever to take sirolimus back in early 2014. And amazingly, thankfully, I was able to make it to Caitlin and I's wedding date. And you wouldn't think this is too important, Dave, but my hair grew back just in time.

He admits that the treatment that works for him has not been shown to work for everyone with Castleman's -- in fact, it appears to help only about 1/3 of those treated with it. But just the fact that it's been helping some is worth noting.

And here's the really interesting part: as we've gone into this whole pandemic thing, many of the participants in the CDCN have noticed some similarities between the issues with Castleman's disease, and with what people are reporting about COVID-19. So they've been repurposing the crowdsourcing effort to work on COVID-19:

DAVIES: So the collaborative that you formed to try and share information and leads about treating Castleman is now focused on COVID-19. I mean, this is obviously an urgent public health matter. Did you see similarities between Castleman disease and COVID-19 that made this a good fit?

FAJGENBAUM: That's right. So early on in this pandemic, it became clear that the most deadly aspect of COVID-19 is actually the cytokine storm that the virus ignites. And the cytokine storm that it ignites is almost identical.

While there are lots of different groups working on different ideas -- from vaccines to antibodies -- the CDCN is focused on what it does best: looking to see if there are FDA approved drugs out there that might have some useful effect here, and recognizing that the only way to really figure that out was to actually get the data (something very few others seemed set up to do):

And so with this similarity between - at the very basic mechanism, what drives the deadliness of COVID-19 is almost identical to what makes Castleman disease so deadly, it's these - the cytokine storm. That was one aspect of it. The second is that we know that drug repurposing is our best shot at identifying a drug that can help patients in the short-term, so a drug that's either already FDA-approved or a drug that is maybe experimental but is not yet approved for anything that could be repurposed for COVID-19. We knew that was our best shot.

And, Dave, I found myself, in early March, thinking to myself, I really hope that some research group out there that has experience studying cytokine storms and has experience doing drug repurposing will follow our blueprint and search for drugs that can be repurposed against this cytokine storm. And I was sitting there hoping that someone would do it.

And then I realized that I needed to listen to my own advice, and that if I'm going to hope that some research lab out there that has experience with cytokine storms and repurposing would turn their effort towards this, then I would need to turn my effort towards this. This is what we've been doing to chase my cure for these years. And we felt like we needed to do what we could in the fight against COVID-19.

The really incredible part here is that he notes that there's no official tracking of the various tests that doctors are doing, and that's a key aspect of what they've set up for doctors around the world:

I mean, you can basically think about the state that we're in right now is that doctors are trying all kinds of things - hydroxychloroquine, remdesivir and many other drugs. Yet there's no system in place to track what's working and what's not working. And so recognizing that this wasn't being done, we decided to build a database, what we called the CORONA database - COVID-19 Registry of Off-label & New Agents. So it's a database to track all of the drugs that have been used against COVID-19 to date 'cause we want to know everything that's been tried, and we want to see what's working and what's not working. And amazingly, almost 150 different drugs have already been tried against COVID-19. And of course, we hear about a handful of them, but there are a lot of others that have already been tried as well. And so we've created this giant database from - right now it's over 11,000 patients and growing - to collect data on every drug that's been used and so that we can really dig into what's working and what's not working.

And the second part of this equation is that you want to track what's being used, but then you also want to piece together all of the data that's emerging from labs around the world to try to map out what are maybe some new drugs that we could start trying to use? What are some new pathways from all of this data that we should start going after? And interestingly, from the state of - we're finding signals that are Castleman-like, basically. A number of the features that we're seeing in the COVID-19 data, these same features we see in Castleman disease.

Think about that first part for a second. In the past, if you wanted to have a database of how certain drugs were used to treat different diseases, and what the impacts of those treatments were, you'd probably need a government to set up a program -- with lots of bureaucracy and mess. But here, a doctor and some other interested researchers were able to set up their own such database on the fly and get a massive amount of data piped into it, from which they can do all sorts of (hopefully!) useful analysis.

This is not to say they're ignoring other approaches -- because these things work together. In the interview, it's mentioned that the crowdsourcing team at CDCN has combed through over 2,500 published papers to look for potential promising treatments.

Also important: they're being very open about all of this. While some keep insisting that we need to lock up successful treatments and ideas, Fajgenbaum recognizes the power of sharing information widely (the very root of crowdsourcing, after all):

You know, what we really want to do with this corona project is to map out everything that's being tried, to put in one place all of the studies that are being published, all of the data on every drug that's being tried so that other people can go to it and they can kind of decide for themselves what looks promising and what doesn't. We didn't build this to say this is the drug and that's not the drug; we built this to say this is where all the data is. If anyone wants to use the data, we have this very data-first approach. Anyone can use the data.

And from our perspective, we want to use the data to determine and to prioritize what drugs should go on to clinical trials. So the fact is, is that this drug is already being studied in randomized controlled trials, and that's all that we can really ask for. We want to use the database to say what's being given, what looks really promising and what should go forward to randomized controlled trial. We don't want to use the database to say this drug should be given or that drugs should not be given. So we're hopeful.

And actually, we put together a paper based on our first pass of analyses of the data and recently received favorable reviews. So hoping that that'll get published in peer-reviewed journal shortly and that we will be able to get the word out about this database. But the goal is not to say this is the drug that everyone should be on; the goal is to say these are the promising drugs. Let's make sure that we don't forget anything along the way because you're right - I think that we all have a tendency to jump on every major drug or every major headline. But we need to keep an eye on all the drugs that are being tried and make sure that we're doing this really systematically.

Once again, the ability for anyone to just setup and build something on the internet, without needing to ask for approval or go through some big bureaucratic process, may be helpful yet again, and hopefully the very open process of bringing in data, and sharing it outward, will lead to real breakthroughs.