Genetic Mechanic: Stanley Crooke on Fixing Nano-Rare Disease with Oligos

He studied pharmacy at Butler University before going on to do an MD PhD at the Baylor College of Medicine.

He then began a career in industry in '75, initially with Bristol Labs, before then joining SmithKline, which became GlaxoSmithKline, or GSK, through the '80s.

In '89, he founded Isis, or Ionis Pharmaceuticals, as it became later known, and had an initial breakthrough through the first approval of antisense oligonucleotide therapies with Vitraven in 1998, which led to a further breakthrough in 2016 through the approval of Spinraza for spinal muscular atrophy.

And you may notice there's a bit of a gap between, uh, the Vitraven [laughs] approval and Spinraza's approval, and there's a reason for that.

The industry went through kind of an upheaval in that time in many ways, which I'm sure we'll get into in the conversation.

But yeah, it's an interesting and fascinating sort of journey that Ionis [laughs] went on.

In 2020, Stan launched a philanthropic endeavor through n-Lorem, a charitable organization treating genetic nano-rare conditions and radically challenging existing dogma around the regulatory and commercial landscape for these conditions.

Soren, you've written quite a lot about n-Lorem.

Do you wanna explain a little bit more about what their work entails?

Yeah.

So n-Lorem is a charity, and what they do is they provide bespoke custom oligo therapies to people with nano-rare conditions.

That means that the fewer than 30 people in the world have that condition.

And these are often very debilitating, often fatal conditions, and there's no commercial opportunity for them.

And the only way to go with this is nonprofit delivery, and so that's what the n-Lorem Foundation does.

It's really cool what they're working on, both in terms of the model that they've built to serve these patients who otherwise would have no options for treatment, and also how it's pushing science forward, which we'll explore over the course of this conversation.

[music] I think maybe to start, I will do what I did last time, which is to give a little bit of a background on the technical side of what we're talking about.

Now, this interview, I don't imagine will be particularly technically heavy.

We're talking about careers.

We're talking about nonprofit models.

We're talking about the pharmaceutical industry.

Like, these are much bigger picture, but I think it's worth knowing, you know, when you hear the, the phrase antisense oligonucleotides, what are we talking about? So antisense oligonucleotides, or ASOs, are very similar to siRNA.

So if you listened to our last episode, you'll have a pretty good idea of what we're talking about in the sense that while the mechanism is different, their main job is to shut off genes at the mRNA level.

And so they bind to mRNA, and they shut it down.

And the other thing that's interesting about ASOs is that, one, they have particularly a strong performance in places like the brain, and the other element that's worth knowing about ASOs is that they are able to do interesting things that are unique to that particular modality.

So more than siRNAs, they're able to do things like alter genes, not just shut them off, so they can remove or cause the machinery of the cell to skip over the disease-causing bits of the gene to produce a healthy version of that gene, and that's a really interesting additional way that ASOs can help treat diseases like Duchenne muscular dystrophy.