Ciliary approach
Cilia are organelles found in many human cells, and come in two types: the motile cilium and the primary cilium. The primary cilium is an extension of the cytoskeleton in contact with the extracellular environment, functioning as a sensory antenna. Mobile cilia perform two types of movement: the push beat, where the cilium curves, and the recovery beat. They also help create left-right asymmetry in internal organs.
The cilia hypothesis suggests that sensory dysfunctions or disturbances in ciliary movements could play a central role in the pathogenesis and development of idiopathic scoliosis.
What we do know
Numerous animal models have shown that ciliary anomalies result in the appearance of scoliotic curvatures.
What we ignore
What are the mechanisms linking ciliary anomalies and scoliosis? How can we make the link between animal models and human beings?
How can we identify the molecular pathways
What advances have been made thanks to research supported by the Fondation Cotrel?
In Paris, doctors Christine Vesque and Sylvie Schneider-Manoury have showed that some genetic alterations lead to changes in certain proteins (rpgrip1) required for the proper development of cilia, resulting in cilia loss at the cellular level. Reproduced in zebrafish models, these alterations produce idiopathic scoliosis.
There are two types of cilia: the motile cilium and the primary cilium. The primary cilium (an expansion of the cytoskeleton) is in contact with the extracellular environment. It can be considered a veritable sensory antenna.
The hypothesis of this line of research is that abnormalities in the sensitive function or movement of the cilia play a central role in the development of idiopathic scoliosis.
This team worked in parallel with Prof. Patrick Edery and Marion Delous (Lyon), who focused their efforts on a ciliary defect in a variant of the POC5 gene.
At Children Hospital Colorado, USA, Prof. Nancy Miller is pursuing her studies with research on the KIF7 gene, a gene identified in certain families with hereditary scoliosis (grandmother, mother, granddaughter, etc.).
Once the mutation has been identified, this team is using an animal model (zebrafish) to understand the implications of this mutation on the primary cilium and on the reasons why a family of proteins – the cytokeratins – are over-represented.
Dr. Jean-François Catanzariti’s team (Villeneuve d’Ascq) used these observations to explore the hypothesis of a physio-pathological link between alterations in cerebrospinal fluid and the presence of scoliosis. However, MRI scans of the brains of 70 adolescents failed to confirm this hypothesis in humans.
The mechanisms linking ciliary anomalies and scoliosis are still unknown.
Research is too recent to have changed patient management.
