Studies explore therapy targets for Chiari-like malformation in dogs

Studies explore therapy targets for Chiari-like malformation in dogs
Charles Maimone, Executive Vice Chancellor for Finance and Administration — North Carolina State University
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A pair of studies conducted by North Carolina State University researchers have explored potential biomarkers and genetic markers related to Chiari-like malformation (CM) in Cavalier King Charles Spaniels (CKCS) and other toy breeds. The research aims to develop targeted therapies for symptoms associated with CM, a congenital condition characterized by a size mismatch between the skull’s cranial vault and its contents, often linked with syringomyelia (SM).

Natasha Olby, Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology at NC State, who is the corresponding author of both studies, explained the complexity of understanding clinical signs of CM and SM due to inconsistencies between symptoms and MRI findings.

Olby noted that “humans with neuropathic pain and migraine have elevated levels of a biomarker called Calcitonin Gene-Related Peptide (CGRP),” which has been effective in treating migraines. However, this biomarker had not been measured in CKCS until now.

In one study involving 29 CKCS, researchers found elevated CGRP levels in dogs with CM experiencing painful symptoms but no correlation between CGRP levels and SM presence. “Although this was a small study,” Olby said, “it points to CGRP as an active pathway in CM.”

The second study focused on identifying genetic markers linked to clinical signs of CM and SM. DNA samples from 179 CKCS were analyzed alongside MRI imaging results. While no specific regions were associated solely with SM presence, signs of pain and scratching were linked to a chromosome region previously connected to skull changes.

Olby emphasized the importance of these findings: “This work confirms the area as a region of interest.” She also highlighted that discovering genetic markers could help breeders reduce disease prevalence through selective breeding.

The research papers are published in the Journal of Veterinary Internal Medicine and BMC Veterinary Research. Co-authors include John D. Macri, Courtney Sparks, Zachary Anderson, Michael W Vandewege, Meghan Leber from NC State; Jonah N. Cullen; Steven G. Friedenberg from the University of St. Paul; supported by several organizations including Cavalier King Charles Spaniel USA Health Foundation.



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