A pair of studies from North Carolina State University looked for biomarkers and genetic markers of a syndrome associated with skull malformations common in Cavalier King Charles spaniels (CKCS) and other toy breeds. The findings could lead to better targeted therapeutics for symptoms as well as potential genetic targets for treatment.
Chiari-like malformation (CM) is a congenital disease characterized by a mismatch in size between the cranial vault of the skull that protects the brain and its contents. The disease is also associated with syringomyelia (SM), a condition where a fluid-filled cavity forms within the spinal cord.
Cavalier King Charles spaniels have a high prevalence of CM and SM, and both conditions can cause neuropathic pain and phantom itching, where the dog scratches at the head and neck without making contact.
"Understanding the source of the clinical signs of CM and SM is complicated given the signs and MRI findings don't always match," says Natasha Olby, Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology at NC State. Olby is the corresponding author of both studies.
"We know that humans with neuropathic pain and migraine have elevated levels of a biomarker called Calcitonin Gene-Related Peptide (CGRP), and antagonists to CGRP signaling have provided some effective migraine treatments," Olby says. "But no one has ever measured the levels of this biomarker in Cavalier King Charles spaniels."
In the first study, Olby and her team looked at 29 CKCS - using imaging, cerebrospinal fluid samples and pain evaluation - and found that levels of CGRP were elevated in dogs with CM and with painful symptoms, but that CGRP levels were not correlated with the presence of SM.
"In people, SM causes pain, abnormal sensations and weakness in extremities, but in dogs, even when we see the condition there may not necessarily be clinical signs," Olby says. "Although this was a small study, it points to CGRP as an active pathway in CM, which presents a potential avenue for future therapy."
In the second study, the team looked for genetic markers associated with the presence of clinical signs of CM and SM.
"The discomfort associated with CMSM is distressing," Olby says. "Finding genetic markers for the disease would not only give us better insight into the disease itself and treatment pathways, it could also allow CKCS breeders to breed away from the trait entirely."
The researchers took DNA samples and did MRI imaging on 179 CKCS. Owners also filled out questionnaires regarding their dog's symptoms and behavior.
The findings were mixed.While no specific regions were associated with the presence of SM alone, the presence of signs of pain and scratch was associated with a region on one chromosome that had previously been associated with skull changes in these dogs.
"We identified a region of interest in a gene also identified by another group using different methods," Olby says. "This work confirms the area as a region of interest and gives us a place to focus our future work."
The papers, "Cerebrospinal Fluid Concentrations of Calcitonin Gene Related Peptide in Dogs with Chiari-like Malformation" and "Cerebrospinal Fluid Concentrations of Calcitonin Gene Related Peptide in Dogs with Chiari-like Malformation" appear in the Journal of Veterinary Internal Medicine and BMC Veterinary Research, respectively. Co-authors from NC State are John D. Macri, Courtney Sparks, Zachary Anderson, Michael W Vandewege and Meghan Leber. Jonah N. Cullen and Steven G. Friedenberg of the University of St. Paul co-authored the BMC Veterinary Research paper. The work was supported by the Cavalier King Charles Spaniel USA Health Foundation, the American Cavalier King Charles Spaniel Club Charitable Trust (through the American Kennel Club Canine Health Foundation grant number 02162-MOU), and the National Institutes of Health (grant number F30OD025357).
-peake-
