Our current research in skeletal, muscular and joint disorders

 

Cell-based assays to detect ‘low-affinity’ antibodies against acetylcholine receptors or antibodies against other neuromuscular junction antigens in canine myasthenia gravis

Research Fellowship Grant: £70,000 awarded in 2023

Institution: University of Cambridge

Myasthenia results from defective transmission at the neuromuscular junction, and is characterised by fatigable skeletal muscle weakness. It can be inherited, but is more commonly acquired (called myasthenia gravis) and is caused by pathogenic autoantibodies targeting the neuromuscular junction. The major antibody target is the nicotinic acetylcholine receptor (AChR), and disease in dogs is confirmed by quantifying AChR autoantibodies using a serological radioimmunoassay (RIA).

A proportion of dogs presenting with suspected myasthenia gravis have no detectable AChR antibodies in this assay, but some are predicted to have low-affinity antibodies against AChRs or other neuromuscular junction proteins. These are not detected by traditional RIA, but could be detected by cell-based assays, as in humans.

Our first Research Fellowship was awarded to a study that will explore whether cell-based assays can detect low-affinity antibodies that are undetected by RIA in dogs with seronegative myasthenia gravis. In future, we expect cell-based assays to be used as a second line diagnostic assay to investigate dogs highly suspected for myasthenia gravis, but who have shown negativity by RIA. An improvement in antibody detection would increase the number of dogs correctly diagnosed that can receive prompt and targeted treatment, resulting in a better outcome.

 

Validation and pathway analysis of biomarkers of canine cruciate ligament disease

Student Research Project Grant: £2,600 awarded in 2023 (funded by The Debs Foundation)

Institution: University of Liverpool

Injuries to the canine cruciate ligament result in severe pain and lameness, and may lead to development of degenerative joint disease such as knee osteoarthritis. They also have a high economic cost, and no current treatments target the prevention of ligament degradation and eventual rupture. This undergraduate project will look at the potential of small molecule biomarkers to indicate disease, and explore the roles they play to identify potential therapeutic targets.

 

Evaluation of synovial cytokine concentrations in dogs with degenerative joint disease, immune mediated polyarthritis and septic arthritis

Clinical Research Project Grant: £2,000 awarded in 2022

Institution: Vet4Life, Teddington

Septic arthritis, degenerative joint disease and immune mediated polyarthritis are painful diseases that can have a devastating impact on the quality of life of affected dogs, and in some cases result in euthanasia. This project aims to identify a biomarker or panel of biomarkers that can be measured on synovial fluid to distinguish between the diseases and help with their prognoses.

 


Past research funded in this area

 

Characterising implant-associated infection and aseptic loosening of total hip replacements in a large cohort of dogs from the BVOA-UoL canine hip registry

Student Research Project Grant: £2,500 awarded in 2020

Institution: University of Bristol

This undergraduate project retrospectively described common radiographic features in cases of septic and aseptic loosening of canine total hip replacement (THR) implants and measured inter- and intra-observer reliability for the radiographic assessment of loose THR implants.

Clinical records and radiographs were obtained for 33 cases. In the first review, notable reported features included periosteal reaction (75.8% of cases), femoral remodelling (72.0%), acetabular remodelling (48.5%), implant subsidence (25.0%) and implant rotation (18.9%). Surgeons deemed the stem sizing and positioning post-THR were correct in 71.2% and 59.1% of cases, respectively. However, these results were inconsistent with the second review. The orthopaedic surgeons correctly identified 27.3–66.7% of cases as septic or aseptic. Inter-rater reliability was 0.03–0.5 for each variable in the first round and all were <0.16 in the second round. These results suggest that even experienced observers have low agreement when assessing radiographs of THR implant loosening, suggesting that septic and aseptic loosening are difficult to diagnose and differentiate between from radiographs alone.

 

Determining predictive metabolomic biomarkers for meniscal injuries in dogs with cranial cruciate ligament rupture using stifle joint synovial fluid

Master’s Degree by Research Grant: £32,927 awarded in 2020

Institution: University of Liverpool

Canine cruciate ligament disease, arising from canine cruciate ligament rupture (CCLR), is one of the most common causes of hindlimb lameness in dogs. Because of its proximity to joint structures that can become altered during disease processes, synovial fluid is a promising source of biomarkers for disease. This master’s degree used proton nuclear magnetic resonance spectroscopy (1H NMR) to examine the metabolomic profile of stifle joint synovial fluid from dogs with cranial cruciate ligament rupture with and without meniscal injuries, to aid the development of a simple minimally invasive test.

154 samples of canine synovial fluid were included in the study from dogs with CCLR without meniscal injury (n=72), those with CCLR with meniscal injury (n=65), and those with no CCLR and no meniscal injury (the control group, n=17). Mobile lipids in the synovial fluid were found to be significantly increased with meniscal injury.

This identification of potential biomarkers of meniscal injury could allow for the development of a simple, inexpensive, minimally invasive test, to diagnose meniscal injuries and reduce the need for surgical diagnosis.

Read our article about the study and access the publication in JSAP