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Disease-Modifying Medical

and Cell-Based Therapy

Susannah J. Sampleand Peter Muir

Introduction

A disease-modifying medical therapy for dogs
with cruciate ligament rupture (CR) remains
elusive. An ideal medical therapy would have
the following features: (i) limit the progres-
sion of osteoarthritis (OA) in affected joints; (ii)
decrease the risk of progressive cruciate liga-
ment fiber rupture in affected stifles; (iii) have
minimal side effects; and (iv) be of reasonable
cost to facilitate potential long-term therapy.
Many barriers exist to the development of a
disease-modifying therapy, perhaps the great-
est of which is the lack of a clear causal biolog-
ical pathway to target. Few studies have eval-
uated potential disease-modifying therapies for
CR in dogs and further research into the distur-
bances to biologic pathways that explain CR is
needed.

Synovial inflammation

Knowledge of the underlying causal disease
mechanism for canine CR is improving over
time. Research over the past decade has estab-
lished that synovitis and joint inflammation
have substantial roles in the disease pathogen-
esis (Hegemannet al. 2005; Muiret al. 2007;

Bleedornet al. 2011). Given the high prevalence

of bilateral arthritis, joint effusion (Chuang

et al. 2014) and contralateral cranial cruciate

ligament (CrCL) rupture (Doverspike et al.

1993; de Bruin 2007; Muir et al. 2011a), the

inflammatory cell populations in synovial

fluid of cruciate rupture-affected stifles (Muir

et al. 2011b), and evidence that inflammation

precedes the development of stifle instability

and complete CR (Bleedornet al. 2011), drugs

that target inflammation seem a logical target

to consider in the development of a disease-

modifying therapy. However, only a limited

number of studies investigating potential anti-

inflammatory therapies have been undertaken.

To date, such studies have met with limited

success.

Tetracyclines

Antibiotics of the tetracycline class, including

doxycycline and minocycline, are potential

disease-modifying therapies for joint inflam-

mation. The tetracycline family are known

to inhibit matrix metalloproteinases (MMPs):

MMPs are degradative enzymes, the upregu-

lation of which by pro-inflammatory cytokines

is a characteristic feature of OA (Fernandes

Advances in the Canine Cranial Cruciate Ligament, Second Edition. Edited by Peter Muir. © 2018 ACVS Foundation.
This Work is a co-publication between the American College of Veterinary Surgeons Foundation and Wiley-Blackwell.

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