Informal report from IntOI 2020+1
A summary by Lidiia Zhytnik, member of OIFE’s Medical Advisory Board
On September 9, 2021 the IntOI 2020+1: Virtual International Meeting Early Stage Investigators Symposium, took place. It was organized by the OI Foundation and chaired by Dr. Joan Marini. The meeting highlighted OI research, performed by young investigators all over the world. The OIFE was delighted to see so many young and enthusiastic researchers. Results from more than 40 OI research projects were carefully selected for presentation on the IntOI 2020+1 Virtual Symposium. In this short summary, OIFE would like to feature some of the knowledge shared with us.
New technologies in bone research
The honour of a basic keynote talk was given to Prof Natalie A. Sims from St Vincent’s Institute of Medical Research, Australia who communicated six new technologies and their application in bone research. According to one of the studies, intravital imaging, used to observe cells inside a living mouse helped to identify new bone cell – osteomorphs. Ostomorphs fuse together to form an osteoclast – a well-known bone cell for everyone with OI. Moreover, scientists could identify this new cell type in the skeleton, by looking at activity of our genes in one single cell (single cell RNAseq). Some of these genes are specially interesting, as they are regulating bone structure, which means they can be used to develop new therapy targets for bone disorders. These and other papers cited by Prof Sims in her talk can be accessed in her Twitter @NathalieASims.
New OI gene KIF5B
Many new things are happening in both basic and clinical research. First of all, a new OI gene is coming (yep, more and more are added to the list). It means that OI gene panels might become longer, but some OI people will finally get their genetic diagnosis. The KIF5B gene apparently causes moderate OI, with full range of typical OI symptoms: fractures, low BMD, short stature, scoliosis, brittle teeth, hearing loss. The defect leading to OI might be connected to transport of collagen. The work was performed by Ronit Marom, Baylor College of Medicine, US.
Variability of OI clinical pictures
Nadia Garibaldi from the University of Pavia, Italy, explored variability of OI clinical pictures. She took a genetic defect, which in some cases lead to lethal, but in other cases to non-lethal OI in mice. Nadia looked on gene activity in mouse cells with this gene defect. According to the study, mice who have lethal OI have more problems with cell skeleton and cell nuclei skeleton. Our bodies have not only a big skeleton, but also tiny protein „skeletons“ inside every cells, which seem to have problems too.
3D bioprinting of bone organoids
In University of Zürich, Switzerland, Timothée Ndarugendamwo with colleagues perform 3D bioprinting of bone organoids (fancy!). An organoid is a simplified mini-copy of an organ, which can be used to test therapies and hopefully substitute mouse experiments in the future, and study disease mechanisms. Scientists take bone cells of people with OI and print them with a 3D printer, layer-by-layer together with a polymer, until a mini-copy of a bone is formed. Bone cells in the mini-bone piece felt fine and could produce collagen.
Development of joint deformation
Joohyun Lim, Baylor College of Medicine, US activated FKBP10 (attention, those with genetic OI type XI) mutations in parts of mice tendons and ligaments and studied development of joint deformations. After exploration of activity of genes involved in formation of joint deformities, researchers were able to affect a network of these genes and partially recover joint deformities.
From skin cells to bone cells
Researchers from Amsterdam UMC, The Netherlands, are working on a cell model for OI. Lauria Claeys has found a way to make bone cells more available for research – just from skin cells. She took skin cells and turned them into stem cells (basically back to the times before birth), and then brought them through different stages to bone cells. According to Lauria: „It will help to test therapies and study OI mechanisms on bone cells without actually needing to take a bone biopsy“.
Bone toughness of young and old mice
Anxhela Docaj, The City College of New York, US studied bone toughness of mice with OI. Scientists looked at the ability of bone to resist fracture and compared it between young mice and older ones. Although bones of adults are tougher, they did not have toughening mechanisms, which younger bones have. Researchers think that this understanding of differences between young and adult bone fracturing will help to prepare special clinical therapies for children and for adults with OI.
Impact of neuraxial anesthesia
At the clinical part of the symposium, Nicholas Bohannon, University of Nebraska Medical Center, US reported results from a study on post-operative pain in OI kids and neuraxial (spinal) anaesthesia. Researchers looked through 611 surgery cases in 194 OI children during 2000-2020. Scientists wanted to compare effect of neuraxial anaesthesia and complex anaesthesia for surgeries on legs. According to the presented results, the use of neuraxial anaesthesia (spinal one) improved pain control, and lead to decreased intake of opioid painkillers. Also, they claim that no adverse events happened in all of the spinal anaesthesia cases during 20 years.
William Querido, Temple University, US studies ways to look at bone quality without irradiation (like DXA and X-rays we are used to). The researcher assessed bone quality in OI people using optical spectroscopy in the visible and infrared range. It could provide information about bone quality similarly to usual DXA scanning and X-rays used in clinic nowadays.
When to start bisphosphonate therapy?
A study of Marie-Eve Robinson, Shriners Hospital for Children, Canada showed that starting bisphosphonates at an earlier age will help to gain more height for those with severe OI (type 3) and moderate OI (type 4), but not for mild OI (type 1). Sorry, mild OI-ers, you still have to go for high heels.
Risk of eye problems in OI
Researchers from University of Southern Denmark, Denmark investigated risks of eye problems in OI people. Marie Louise Lyster has studied records of 907 OI people, from 1977 to 2018. According to the results, people with OI have higher risks of eye diseases compared to non-OI people – it appears that we have to keep an eye on our eyes, guys. The whole interview with Marie Louise can be found here.
Inclusion of students with OI
McGill University/Shriners Hospital for Children, Canada presented by Jessica Chemtov shared a creation of a tool which will help for optimal inclusion of students with OI. Jessica created guidelines and recommendations for integration of OI kids in primary and secondary school. Important items of the guidelines for inclusion of OI students are listed here: general information about the student, fracture response protocol, student inclusion recommendation, mobility considerations, transfer consideration, toileting protocol, physical education class recommendations, fieldtrip information, transportation considerations, evacuation plan, seating and scholarly considerations, consent and authorization forms and an annual renewal document. Researchers concluded that there should be a collaboration and partnership between school and health care centre of the child.
Information about the rest of OI research projects performed by young professionals and presented on the event can be found in the abstract book of the symposium. We would like to express our kind support and admiration to everyone who work on OI and advances OI research. You can watch the whole recording of the conference on YouTube.