The Foundation is always looking into research projects that directly benefit the health of our breed. We look to our supporters for their constant input, donations and support. We thank you. Please feel free to email us with questions or suggestions at askthefoundation@gmail.com
The studies updated here as follows. Scroll down for the details.
- GLAUCOMA
- HEMANGIOSARCOMA (CANINE CANCER – 2 STUDIES)
- IMMUNE MEDIATED HEMOLYTIC ANEMIA (IMHA) – 2 STUDIES
GLAUCOMA
Glaucoma is a leading cause of irreversible blindness and globe removal (enucleation) in dogs. Clinical signs of the disease are:
- Squinting
- Corneal edema (a white haze)
- Tearing
- Loss of sight
- A bright red, bulging eye (called buphthalmos)
- Dilated pupils
- Lethargy
- Lack of appetite
- Dilated or slow-moving pupil
- Pain
Primary angle closure glaucoma (PACG) is the most common form of glaucoma in dogs whereby acute blockage of the iridocorneal angle leads to a rapid increase in intraocular pressure. Consequently, it is painful, demands immediate medical attention, and often causes incurable vision loss. The American Cocker Spaniel (ACS) has the highest reported prevalence of any canine breed.
PACG in canines is epidemiologically and clinically similar to humans. The morphological observations that characterize this disease include the collapse of the Ciliary Cleft followed by its narrowing as well as that of the iridocorneal angle.
The ACSs showed unique features consisting of posterior bowing of the iris and longer iridolenticular contact, which mirrors reverse pupillary block and pigment dispersion syndrome in humans. The ACS could hold the potential to serve as an animal model of naturally occurring PACG in humans.
Despite the high prevalence of PACG in ACS, what makes ACS more susceptible to PACG development in comparison to other canine breeds remains unknown. In the present study, GWAS failed to identify candidate loci associated with PACG in ACS. This result in combination with the high incidence of PACG in ACS reiterates that canine PACG could be a multifactorial disease having complex genetic traits.
Dr Sara Thomasy, University of California at Davis, has been the recipient of Funds from AKC -CHF to study the genetics of the disease hoping to identify the variants that cause PAGG. THE FOUNDATION proudly supported this work both in monetary contribution as well as contributing cases for the study.
HEMANGIOSARCOMA (2 STUDIES)
Hemangiosarcoma is an aggressive and common form of canine cancer. It is known as the silent killer. Although the cutaneous masses are often treatable by surgery the visceral tumors are almost always incurable mostly due to the lack of detection as well as the extent of their location.
The biology of this type of cancer is still not clearly understood. The histological evidence appears to indicate a transformation of endothelial cells, although recent data suggests a pluripotent bone marrow progenitor as the cell of origin for this disease.
The ASCF has a long history of supporting research for this disease. The recent grant ASCF supported has reached its conclusion this year. Dr Erin Dickerson of the Univ. of Minnesota sought to evaluate in a clinical trial the use of Propanolol and Doxirubicin combination in the treatment of this disease.
Angiosarcoma in humans is strikingly similar to hemangiosarcoma in canine. Published reports have shown that the use of Propanolol, used to treat heart disease in humans and canine has been shown to substantially increase the survival times of the human patients when used in combination with chemotherapy agents. Propanolol has been shown to substantially sensitize hemangiosarcoma cells to doxorubicin thereby increasing the effectiveness of the drug.
The findings show that 40% (8 dogs) of the dogs have survived for more than six months, 30% (6 dogs) have survived for more than 9 months, and 15% (3 dogs) have survived for more than two years. One canine patient diagnosed at the age of five has lived over 3 years with this treatment combination.
Importantly, the dogs surviving > 2 years were diagnosed with hemangiosarcoma at age five, suggesting occurrence at the age of five or younger may be a predictor of a favorable outcome. No one treatment will effectively cure this disease.
THE FOUNDATION’s continued support for the research on this devastating disease has concurred with sponsoring 2 additional CHF-approved grants. Each grant has different treatment approaches. One grant is carried out by Dr. Rowwan Milner and the team at the Univ. of Florida titled A GD3 Nano-scaled liposomal cancer Vaccine trial for Canine HSA
This research proposes to use a vaccine that investigators have extensive experience with canine melanoma and osteosarcoma (bone cancer). New preliminary research indicates that the vaccine target, GD3*, is present in HSA, similar to melanoma and osteosarcoma use. All dogs will get standard-of-care treatment and be randomized into two groups – one getting the GD3-based vaccine and the other group receiving a placebo. Since melanoma and osteosarcoma have shown promising results, investigators hope that dogs with HSA respond similarly to the vaccine.
GD3 is a ganglioside a liipid-oligosaccharide molecule used as a tumor marker.
The second grant is under the direction of Dr Timothy Fan of the Univ. of IL. Is titled: Suppression of Extracellular Glutamate Efflux & mGluR1 Signaling to Impede Canine Hemangiosarcoma Cell Growth
This investigation explores extracellular glutamate efflux and metabotropic glutamate signaling in sustaining cHSA cell proliferation. If the investigators’ hypothesis is true, current FDA drugs can be repurposed to inhibit glutamate efflux and serve as novel adjuvant strategies for curbing the explosive outgrowth of cHSA cells. Targeting the metabolic dependency of glutamate efflux and consequent paracrine metabotropic signaling could improve the clinical management and survival of pet dogs afflicted with this deadly vascular malignancy.
IMMUNE-MEDIATED HEMOLYTIC ANEMIA (IMHA). – 2 Studies
IMHA (Immune-mediated Hemolytic Anemia) is a life-threatening autoimmune-triggered disease. Affecting both canines and humans it is known as Autoimmune Hemolytic Anemia (AIHA). In both species the disease shares a common pathogenesis involving polyclonal IgG autoantibodies directed against Red Blood Cell surface antigens; hemolysis mediated by hepatic and splenic macrophages; a comparable balance of primary and secondary causes; a nearly identical clinical course; and highly similar treatment options.
Although the disease occurs in both humans and dogs, it is 10 times more prevalent in dogs and the Cocker Spaniel and Springer Spaniel are the most susceptible breeds for developing the disease.
In general, the immunological, cellular, and genetic mechanisms that cause IMHA are not well understood in dogs. No primary antigenic target has been established. Although a genetic link has been suggested in several breeds, no genetic variant has been identified so far. Veterinarians classify IMHA into 2 categories Primary non associative and Secondary associative,
Pale gums and blood smear showing spherocytes, and smaller RBC lacking the central pallor are indicative of the disease.
THE FOUNDATION has always supported research in this area considering the prevalence in our breed. We strongly support the research carried out by Dr Stokol at Cornell University, titled: Plasminogen-activator Inhibitor-1 (PAI-1) and Impaired Fibrinolysis in Immune-Mediated Hemolytic Anemia
In the course of the disease along with the hemolysis of the red blood cells, disseminated blood clots are formed. The main objective of this study is to correlate if the high protein level of the PAI-1, the main inhibitor of fibrinolysis, is the cause for the defective breakdown of blood clots formed. The implications of these findings could modify the medical treatment.
Dr Stokol has expanded the group of veterinary centers collaborating on the project to increase the number of case studies. These include Dr. Steven Friedenberg at U. Minnesota, and Dr Dana LeVine at Auburn, AL. Dr. Shauna Blois, Ontario Vet College, Guelph, Dr. Joel Weltman Animal Medical Center NYC., and Dr Benjamin Brainard, Georgia.
The eligibility for this study requires that only dogs who have not been treated for IMHA with immunosuppressive drugs (such as prednisone or other steroids) or anticoagulants (such as aspirin or heparin) before enrollment are eligible. The owner will be asked to allow for an additional blood sample. There will be no charge for the additional tests run on your pet and no further obligations.
For additional information, you may contact
Name: Clinical Trials Coordinator
Phone: (607)-253-3060
Email: vet-research@cornell.edu
THE FOUNDATION is also asking the membership to support this research study:
“Understanding the genetics of immune-mediated hemolytic anemia(IMHA) in Spaniel breeds.” under the supervision of Dr Steven Friedenberg of the University of Minnesota Veterinary College.
Dr Friedenberg has solicited funding to study AIMA using the canine model in particular the Cocker Spaniel (American and English) and the Springer Spaniel since they offer an exceptional naturally occurring model for studying genetic risk factors and T cell biology.
The main objectives are to:
- Identify genetic risk factors for AIHA in dogs.
- Characterize the autoreactive T cell population and peptide epitopes in canine.
To carry out this project Dr Friedenberg requires
—blood samples from Cocker Spaniels who have had IMHA in the past
—blood samples from Cocker Spaniels with a new diagnosis of IMHA
—organ tissue samples from Cocker Spaniels who recovered from IMHA and are nearing the end of their life (for any reason) would be willing to donate tissue samples after they have passed
If you would be willing to help, please contact him at imha@umn.edu. He can walk you through the process. His study will pay for all expenses.
