Investigation of potential genetic biomarkers of chronic recurrent multifocal osteomyelitis (CRMO)

Summary

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteitis, is a rare inflammatory bone disease with onset predominantly in childhood.  Characteristic features are bone pain and swelling and, if undiagnosed and inadequately treated, it can lead to long-term pain, bony deformity and disability.  After non-steroidal anti-inflammatory drugs, there is no consensus on second-line treatments which include bisphosphonates, such as pamidronate, and anti-tumour necrosis factor (TNF) drugs.   The genetic basis and optimal treatment of CRMO are currently unknown.  Identification of genetic variants associated with CRMO may aid with diagnosis and help to predict the course of disease and response to treatments.  In Bristol we have a unique cohort of 32 well-characterised CRMO patients who have provided blood samples and consent for DNA analysis.  We plan to use modern, efficient genetic sequencing techniques to search for potential disease-associated variants in this cohort.  We are also developing a proposal for a randomised controlled trial to investigate the effectiveness of pamidronate versus adalimumab (an anti-TNF drug) for treatment of CRMO for submission to the NIHR EME grant programme.  Genetic findings will be extended as part of studies into the mechanisms of disease in a larger cohort of patients as part of the NIHR application.  The intention is that genetic testing will help with the diagnosis and allocation of patients with CRMO to the most effective therapies.

Work to date

Sixteen patients with chronic recurrent multifocal osteomyelitis (CRMO) have been identified from the Bristol cohort.  Their blood samples, together with samples from a parent (and in two cases both parents), have been transferred to Bristol Genetics Laboratory(BGL) for DNA extraction.  BGL have purchased and installed new DNA sequencing equipment and have been completing quality control checks before use on research samples.   The first five CRMO patients with most typical presentation have been selected for the first sequencing cycle which is due to take place within the next 2 weeks.

Project outputs

No abstracts / publications so far.  The work will contribute to the PhD of Dr Ethan Sen, Specialty Registrar in Paediatric Rheumatology, Bristol Royal Hospital for Children, and NIHR Rare Disease Translational Research Collaboration (RD-TRC) Clinical Research Fellow,  University of Bristol.

Further funding applications

This project has led to an Arthritis Research UK research grant for £21,010.

Other project outcomes

The project has further developed academic collaboration between Bristol Royal Hospital for Children, in particular the Department of Paediatric Rheumatology, and the Bristol Genetics Laboratory with their expertise in exome sequencing and bioinformatics.

Updated October 2016