Health and Education Report

Grant Updates and Project Overviews

Fall 2007, NEWS

Legg-Calve-Perthes (LCP) Disease
Investigator: Keith Murphy, Ph.D., Professor, Texas A&M CVM
Health Task Force Chair: Kay McGuire, DVMPatrick Venta, Michigan State University

What is it? LCP is a spontaneous degeneration of the head of the femur and neck. The disease leads to a collapse of the coxofemoral joint and arthritis. Most patients demonstrate signs between 5 – 8 months with a range of 3 – 13 months. The disease is usually unilateral with between 12% - 16% bilateral. Lameness is gradual with an onset over 3 – 4 months. Untreated, the Westie becomes lame on the leg and suffers pain with movement of the leg and degeneration (atrophy) of the thigh muscle. The precise cause of the disease is unknown. However a genetic predisposition is likely. The disease is one of the top five diseases reported in the Westie Foundation of America and West Highland White Terrier Club of America 2007 Health Survey.

How will this study help? Dr. Murphy and his team will attempt to find the DNA linked marker for the disease. If they can identify the linked marker, the isolation and identification of the direct marker of the mutant gene that produces the disease might be possible.

Characterization of the Clinical Features of Idiopathic Pulmonary Fibrosis in the West Highland White Terrier
Investigator: Brendan Corcoran, MVB, PhD
Health Task Force Chair – Fred Askin, MD

What is it? Idiopathic Pulmonary Fibrosis (IPF) is a complex of diseases that affects the lung air sacs (Alveoli). The disease is predominately seen in the West Highland Whiter Terrier but has also been noted in the Cairn and Bull Terrier. The disease is progressive with the lung sacs becoming fibroid making breathing difficult.

Final Report – The purpose of this study was to attempt to improve the clinical description of the disease in the West Highland White Terrier, to verify the existence of IPF, to see if specific diagnostic criteria could be identified and to investigate the involvement of or association with chronic bronchitis.

The initial design of the study was to recruit 20 cases of WHWTs who were middle age and who had evidence of chronic progressive lung disease from three veterinary school centers in Scotland (University of Glasgow and University of Edinburgh) and the USA (University of California and University of Pennsylvania). A total of 26 cases were recruited with only 22 cases meeting the criteria of a case.

Results – this is the first study to document prospectively the clinical and diagnostic features of the West Highland white terriers affected by putative Idiopathic Pulmonary Fibrosis (IPF). The intention of the study was to see if the accuracy of diagnosis of IPF in the WHWT could be improved and the overall clinical phenotype described in detail. This study is to be the first of several that would allow further studies on a clinically well-defined population to be undertaken in the future. It is hoped that further studies will allow for clinical treatment protocols and to eventually lead to causation of the disease and preclinical detection test.

In this study, the researchers also used High Resolution Computed Tomography (HRCT) in the di- agnosis of IPF. They were able to identify a series of changes that had more close similarity to those changes reported for human IPF patients. On the basis of this work, they decided to further investigate the clinical phenotype of WHWT IPF using standard diagnostic test and HRCT. What did change in this study compared to a previous 1999 retrospective study conducted on 33 WHWT was that they identified many more dogs that had chronic bronchitis and an additional group that had a combination of IPF and chronic bronchitis. They also identified dogs with a distinct evidence of lone IPF. For all three clinical presentations the clinical history is indistinguishable and no distinction could be made on physical examination or routine hematology or chemistry profiles. Bronchoscopy was crucial in the identification and confirmation of chronic bronchitis, either as the sole condition or in combination with IPF. This is significant to the pet owner because treatment for chronic bronchitis can follow a different approach than IPF or IPF combined with chronic bronchitis. While HRCT allowed for the identification of bronchial changes greater than radiology. Many veterinary specialists do not have immediate access to HRCT unless it is at a major university. However bronchoscopy is a diagnostic technique that can be conducted at major internal medicine and cardiovascular specialty practices.

Dr. Cochran can state with reasonable confidence that IPF in the WHWT is a slowly progressing respiratory disease of middle aged dogs, which present with one or a combination of coughing, dyspenea and exercise intolerance, but are otherwise healthy dogs, have no evidence of chronic bronchitis on bronchoscopy and have radiographic or HRT evidence of an increase interstitial pattern.

With this clinical phenotypic description it is hoped that IPF will be more accurately diagnosed in the future. The strength of the diagnostic descriptor would be greatly enhanced by data from other dogs, but also by correlation with pathological findings. Our foundation with your support hopes to the latter will be carried out at some time in the future.

One of the biggest failings in this study was the availability of cases. No cases of IPF were identified at the University of California – Davis. Less than 10 cases were presented to the University of Pennsylvania. With less than 60 cases being in the study, there was not sufficient data for statistical analysis. For continual research in this disease, our foundation will need to ensure researchers’ sufficient cases for their study. A volunteer to serve as the Task Force Chair is needed to coordinate cases and provide information to Westie owners who have this disease. If you would like to volunteer to be on this group or chair this group, please give Dr. McCaskill or Dr. Askin a call or email.

Dr. Cochran will present his research at the International IPF WHWT and human Comparative Respiratory Society Meeting in Purdue University College of Veterinary Medicine in October 2007. Additionally he will publish his research in an appropriate general clinical journal, such as the Journal of Veterinary Internal Medicine.

Investigation of Antigenic Causes of Vaccine-Associated Allergic Reactions in Dogs
Investigation: George Moore, DVM
Health Task Force Chair– Bob McCaskill, DVM

Why is it important?: The WHWT is 34 on the list of pure breed dogs subject to adverse reactions to vaccines as reported by a Oct 1, 2005 JAVMA article (Moore and Glickman). If scientific information was available on antigen-specific IgE concentrations in affected vs. non-affected of the same breed and of different breeds, it would allow a more complete understanding of the phenotype of the disease and the immune systems response to vaccines.

Progress: Dr. Moore and his team reports that they are in the process of distributing and collecting samples from veterinarians. They expect that this will last six months and they expect to collect sufficient samples to complete their second objective. The second part of their study will be to measure sera for antigen-specific IgE concentrations. They expect to complete this objective in the second year of their study. Dr. Moore anticipates completing this grant with no difficulty.

Dr. Moore is an internationally known veterinary epidemiologist and is available to speak on the risk factors for vaccine reaction. Our foundation may consider him for a future education seminar.

Linkage Analysis of Craniomandibular Osteopathy (CMO) in Terrier Breeds
Principal Investigator: Patrick Venta, PhD
Health Task Force Chair– John Robinson, DVM

Why is it important? CMO is one of the top important diseases to the WHWT. CMO is an inherited non-cancerous overgrowth of bone primarily found in the jaw region of affected Westie. The disease generally disappears about a year after the initial onset at several months of age. It is rarely fatal, but can cause pain to the puppy and a good deal of distress and health cost to the owner. Identifying a linked marker to the genetic cause of the disease would lead to a direct marker of the mutant gene. This would allow for a genetic test that would identify carrier and potentially allow for the elimination of the disease through sound breeding programs.

Progress: A genome scan for the CMO gene by pedigree-based linkage analysis has been partially completed. This analysis will continue and our investigator reports that they will also attempt to use several commercially available DNA enhancement kits and faster genotyping to supplement their manual system of DNA identification from cheek swabs. If necessary, they will go chromosome by chromosome until they find a linked market to the gene.

Forecast: Dr. Venta is a highly skilled and ethical researcher. He has been working on this complex disease with the foundation since the foundation started. He has been flexible in his research in adopting the latest test means in this fast moving research area. He is using complementary funds to augment our study and have been able to use other screening tools to provide solid research progress.

Histocompatibility Alleles Conferring Susceptibility to Canine Diabetes, Immune-Mediated Thyroiditis and Immune-Mediated Hemolytic Anemia
Investigator: Wayne Potts, PhD

What is it? Canine diabetes, immune- mediated thyroiditis and immune-mediated hemolytic anemia are immune disease complexes that occur in the WHWT. Although not identified as one of the top disease entities in the WHWT, our foundation felt that several resources were sufficient to support this grant.

Progress: This research as been in progress for three years. The researchers report that they now have all the targeted samples. They will begin gene sequencing. The researchers applied for and were granted a No Cost Extension to let them finish this sequencing project.

Candidate Gene Analysis in Dogs Affected with Hereditary Cataracts
Investigator: D.J.Sidjanin, PhD
Health Task Force Chair– Bob McCaskill, DVM

What is it? Juvenile cataracts are a disease found in the WHWT. It was identified as one of the top diseases in the 2000 and 2007 WHWT Health Survey. Believed to be genetic in origin, it affects young Westies causing pain and expense to the Westie owner.

Progress: Dr, Sidjanin reports that they have optimized experimental conditions to evaluate seven genes that could be harboring mutations responsible for hereditary cataracts in several breeds. Thus far they have identified no mutations. They will continue with evaluation of additional genes in a hope that they find the causative mutation for canine hereditary cataracts.