CSO Corner Volume 12: Watching Things Come Together on the Clinical Side

Hello fellow members of our KS family! 

This month I’d like to do something a little different and lead us all on a bit of a victory lap. Why? Thanks to your work and your support, we are really putting together a nice string of wins on the clinical side. We should all be really happy about this, and then we should double down.

It is useful to think of getting to a treatment for KS as having two great arms. One arm is finding pre-clinical drug candidates that could become a future treatment. But the other arm is becoming clinical-trial-ready as a condition, so that when potential treatments are found they can be validated in patients. 

Recently I was meeting with a biotech company and presenting KS as a condition they should be interested in, and I realized the KS community is now really on track to achieve clinical trial readiness. As the company asked me questions about KS, I found I had all the answers they were looking for: “Q: How many confirmed patients do you have?”, “A: We know our patient numbers and we have a map, with patients that have agreed to be contacted.”¹

And we:

Have a clinic at Boston Children’s.

Received our ICD-10 code. 

Recently  published our disease concept model. 

Have a great presence on Rare-X and Citizen Health.

Are part of biomarker study.

Have started a natural history study.

(etc.) 

We are doing this, together!

By now a lot has been said about the new natural history study, and we’ve shared a lot about how you can get involved. If you’re still on the fence, I’ll return to that aspect below. But I’d like to spend a little time explaining how this study fits into the overall strategy.

The key aspect of a natural history that makes it special is that it is prospective. A group of the same patients, at planned one-year intervals, are seen and given the same assessments and clinical tests. This is really powerful data, because it removes a lot of the noise present in other approaches. 

For example, when we look at the same patient at 3,4, and 5 years of age with this approach, the only thing changing is the patient’s age. We can then see how that patient progresses on the same assessments, just changing that one variable. Now compare that, for example, to looking at three different patients simultaneously, one at 3, one at 4, and one at 5 years old. In this approach there are many variables, including genetic variant, home environment, etc. With the right procedures, it’s not impossible to generate good results with this approach, but it’s a lot harder. This is why the prospective natural history studies are considered the “gold standard” in establishing clinical trial readiness.

Hopefully I’ve convinced you how important this study is going to be! But you may be wondering: if we are doing this study, why are we doing other efforts to establish natural history, like Rare-X and Citizen Health? The answer is that these approaches are complementary.

I’ve previously covered Rare-X and Citizen Health, so I won’t go into depth on them here, but the key fact is that these are retrospective approaches. They look at patients going from now, backwards. Insights can be revealed by mining this data and looking into where patients were at certain ages, and how they changed. 

This approach has its own advantages. For one thing, we have the data right now, we don’t have to wait years to collect it. Also, we can sample across more variables (and different types of data) than in a prospective natural history study, since we don’t have the limits of having to see the patients in a clinic to get the data. And then there is perhaps the biggest benefit of all: this data can scale massively. Our community currently has about 150 patients in both Rare-X and Citizen Health. That is one heck of a dataset for scientists to mine!

So, let’s come back to that doubling down part:

Potential treatments may be found by us, or by others. But for clinical trial readiness, there are no “others” to do the work. We can’t get there without community participation! So once again, I’m going to ask you to lean in on these efforts.

Natural History Study

If you’ve been on the fence about being a part of the natural history study, recruitment is still ongoing. Please review the information, and if you are interested, contact zoe.frazier@childrens.harvard.edu to learn more and get any additional questions answered. All you need to do is send that one email to get the process started!

Rare-X

If you haven’t yet enrolled, you can do so here: https://rare-x.org/kleefstra/. If you already have, thank you! But please log in and make sure you have done all your surveys. This is the key data needed for Rare-X to work.

Citizen Health

If you haven’t yet enrolled, you can do so here: https://www.citizen.health/partners/kleefstra-syndrome (One other note: I’ve been beta testing some new features on this site, and while I can’t yet share them, they are super cool. Stay tuned!)

Until next time,

Eric Scheeff, PhD

IDefine Chief Scientific Officer 

1. Side note: we are edging towards 1,000 patients on the map, exciting times! [↩]