By Dr. Lars Folkestad, OIFE Medical Advisory Board

Every year the OI Foundation (OIF) host a Scientific Meeting where researchers and clinicians from North America is invited for a 2-and-a-half-day long seminar focused on OI research. Lars Folkestad, member of OIFE’s Medical Advisory Board, joined the meeting in April and reports about it.

Collaboration between OIF and OIFE

This year’s meeting was chaired by Ken Kozloff (left side of the photo) from the University of Michigan. As part of the collaboration between the OIF and the OIFE, I was invited to participate and present data from the Danish OI Register-Based Cohorts Studies that I have been working on for the better parts of 1,5 decades now. I would like to start by thanking both the OIF and OIFE for giving me the opportunity to participate.

Arrival

I flew in Tuesday night and had a day to myself before the meeting. I took a walk in downtown Chicago and went on the ‘architectural boat ride’ – which takes on the Chicago River along many of the impressive high-rises and skyscrapers that make out the Chicago skyline. I am always impressed by these buildings, and it was nice to have a little time to see the big city.

Newest animal model methods

The meeting started with a keynote presentation by Matthew Warman, who updated us on the newest animal model methods that are being used to produce OI mouse models with tissue specific phenotypes. In a near future, it will be possible to evaluate the respiratory system in a mouse, without having a mouse with severe skeletal problems in addition. This talk set the scene for what day 2 had in stall. Most of the talks covered the bone, cartilage, muscle cross talk and underlined again and again that you cannot have the one without the other.

A talk that stood out for me, was the from Roy Morello, who has now produced a mouse model where you can turn on a specific OI mutation at any given time during the mouse lifetime. And you can do so in a tissue specific way. This means that you can have a mouse with healthy non-OI bones, but OI muscle function – or a mouse with OI affected lungs, but no OI affected bones. The implication being that researchers will now be able to look at tissue specific outcomes without the doubt that we often have: Is what we see in this tissue related to OI related collagen changes or due to bone deformities that themselves give problems in other organs? One example of this dilemma would be lungs and scoliosis. Is the dyspnoea seen in some people with OI, related to changes in the lungs, or secondary to scoliosis and/or fractures to the spine and ribs?

This new model (that do not have a name yet) will be able to differentiate, or in other words, look at OI related lung changes and OI bone related lung changes depending on where the researcher activates the mutation. For a clinician and clinical research like me who has never worked in a lab (sadly), this is nothing short of magic.

Natural history study by Brittle Bones Disorders Consortium

On the last day there were two sessions. The first updating us on the Brittle Bones Disorders Consortium (BBDC) studies – which is a large natural history study now including 1000 persons with OI from North America. The population have been followed in a systematic fashion, with a large body of data being collected. Just one example would be that the researchers have collected 4000 x-rays, mainly focused on fractures to the spine, prevalence, and severity of scoliosis. But also other bones have been evaluated. There are genetic screening and clinical evaluations of all participants.

And looking at what studies the working group have planned, we can expect very interesting results from this study over the years to come. One key aspect of the study is to evaluate if a participant would fit into one of the many clinical treatment pathways that are set up using novel drugs to target different disease specific pathways in OI. These can be to improve bone heath, reduce fracture risk and reduce pain. It was during this session that I gave my talk, and after a day of single cell studies I was a bit nervous that coming with population data would be a bit off topic. But the discussion was lively, and the questions had me on my toes. But it was fun, and I got some good points to follow-up on.

Personal conclusion

For me personally it was very special to be in a room with who’s-who of OI research in US and Canada, and I really enjoyed the discussions in the breaks, being invited out to eat after a long day of science and generally just bumping into people who had read my papers and who I have read many papers by. I really hope I will be invited back, because this was the best OI meeting I’ve been to since before COVID. Being able to actually shake hands with people is something that should not be disregarded as trivial. Yes, we can always Zoom! But sitting down at a table, talking about everything from stories about Dr. Raggio’s dog to growth curves for Canadian children with OI, and not worry about remembering to unmute yourself, just makes for a better conversation.

This article was first published in OIFE Magazine 2-2023.