Research

Imagine

Searching for Causes and Treatments

Imagine the day when hearing the word hemangiosarcoma doesn’t mean you will be immediately saying goodbye to your Leonberger companion. Or an osteosarcoma diagnosis doesn’t mean a slow, painful decline to the inevitable. Can you even imagine when future Leonberger owners won’t know about a diagnosis of early-onset polyneuropathy? Not only can the Leonberger Health Foundation imagine it, the LHF is working with world-renowned scientists to make it a reality!

Since its inception, the LHF has supported research to find the causes and treatments for the diseases that kill, maim, and affect the quality of life in Leonbergers around the world. Working with scientists, and then breeders, the LHF hopes to find a way to eradicate many of these diseases from the Leonberger population. And, if complete eradication is not possible, then find ways to treat the diseases so everyone can look forward to a better prognosis and additional time with their beloved companions.

Please join us in the fight to improve the quality of life, health, and longevity in our Leonberger companions!

Leonberger Polyneuropathy (LPN)

Hemangionsarcoma

Osteosarcoma

Cryptorchidism & Infertility

Addison's Disease

Inherited Leonberger Polyneuropathy

Polyneuropathy is a neurologic disease which affects multiple nerves. In the case of LPN, it is the longest peripheral, i.e. nerves outside of the spinal canal, which are most severely affected. LPN is characterized by worsening exercise intolerance and the development of gait abnormalities, especially in the hind limbs. Affected dogs may also have noisy breathing or difficulty breathing due to involvement of the larynx. Click here to see video depicting LPN symptoms.

The relationship between the Leonberger Health Foundation, the University of Minnesota, and the University of California, San Diego, began in 2003 for the purpose offinding the causes of LPN. In 2008, the University of Bern in Switzerland joined to collaborate on LPN research.

From the University of Minnesota: Research carried out at the University of Minnesota, the University of Bern, and the University of California San Diego, indicates that polyneuropathy is likely a group of several genetically distinct, but clinically similar diseases. We have mapped two major genetic risk loci and identified the causative mutation in one of these loci that we now term LPN1. Dogs being homozygous mutant (two copies of the mutation) for this mutation will typically develop neuropathy before they reach 3 years of age. Dogs heterozygous for this mutation (one copy of the mutation) might also develop mild clinical signs late in life, but they will most likely not develop severe disease. The identified LPN1 mutation appears to be responsible for approximately one third of the cases of polyneuropathy in Leonbergers. The other two thirds of cases are apparently caused by different genetic mutations.

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The face of LPN1 - Aslan was diagnosed with LPN at 1 and has since tested as homozygous for the LPN1 mutation

Genetic Test for LPN1 Announced! On June 17, 2010, the University of Minnesota and the University of Bern announced a genetic test for LPN1. Starting in July 2010, all Leonbergers have the opportunity to be tested for the LPN1 gene mutation! For more information on LPN1, please review the following:

LPN1 Genetic Test Announcement

Testing for LPN1

View a video of LPN affected dogs

How you can help LPN Research

Understanding LPN

LPN Update September, 2011

Hemangiosarcoma

Hemangiosarcoma is an aggressive malignant tumor of blood vessels. Hemangiosarcoma is rarely curable and long-term prognosis is usually poor. There are few or no discernible signs of hemangiosarcoma before severe clinical onset of symptoms, including sudden death from blood loss due to a ruptured tumor.

In 2005, the Leonberger Health Foundation forged a relationship with the Broad Institute and principal investigator, Dr. Kerstin Lindblad-Toh, PhD, to understand genetic risk factors for hemangiosarcoma. The Leonberger Health Foundation supported this important research with not only grant dollars, but also by facilitating the collection of DNA/blood samples from hundreds of healthy and affected Leonbergers.

Most recent update from the Broad Institute: After comparing the genomes of ~100 healthy dogs with ~100 dogs with HSA, we were able to identify several areas of the genome that were possibly associated with inherited HSA risk factors. Currently, five genes found to be associated with the disease are being searched for mutations. Once the mutations have been identified and their presence in different breeds assessed, this will allow for rapid development of genetic tests for carriers of HSA. From Broad Institute Dog Disease Research

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The face of Hemangiosarcoma – Einstein succumbed to the disease in January, 2009

In 2009, The Leonberger Health Foundation provided funding for “Identifying Mutations in Genes Associated with Canine Hemangiosarcoma” to Tufts University. A final summary of the completed work can be found by clicking here.

Funding for a grant to look for targeted therapies in hemangiosarcoma has been provided to the University of Pennsylvania and primary researcher Dr. Nicola J. Mason, BVetMed, PhD in 2009 and 2010. A recent update can be found by clicking here.

How you can help Hemangiosarcoma Research

Osteosarcoma

Osteosarcoma is a malignant tumor of the bone, and although it can occur in any bone, is most likely found in the limbs of our Leonbergers. The tumor starts deep in the bone, causing pain as it grows outward. The most common symptom is lameness.

In 2005, The Leonberger Health Foundation forged a relationship with the Broad Institute and principal investigator, Dr. Kerstin Lindblad-Toh, PhD, to understand genetic risk factors for osteosarcoma. The Leonberger Health Foundation supported this important research with not only grant dollars, but also by facilitating the collection of DNA/blood samples from hundreds of healthy and affected Leonbergers. All support continues today.

Most recent update from the Broad Institute: To date, we have collected ~500 blood samples from dogs diagnosed with OSA and ~1500 from healthy dogs over 8 years old. We have localized genetic risk factors that are associated with OSA to three chromosomal regions in greyhounds, as well as three chromosomal regions in the Rottweiler breed, and are currently narrowing in on the precise mutations that cause the disease using ten different breeds. The biological effects of the mutations will be studied to better understand the cause and progression of the disease.

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The face of Osteosarcoma – Okemo succumbed to the disease in February, 2009

For additional information on the Osteosarcoma work being completed at the Broad Institute, please click here.

In 2008, the LHF provided funds for a study of “Heritable and Sporadic Genetic Lesions in Canine Osteosarcoma,” conducted at North Carolina State University with Dr. Matthew Breen, PhD. This grant is ongoing and the most recent progress report can be found by clicking here.

Also in 2008, the LHF provided funding to investigate “the Role of STAT3 Activation in Canine Osteosarcoma,” at Ohio State University. A final summary of the work can be found by clicking here.

In 2010, the LHF is supporting the study of a targeted therapy for osteosarcoma at the University of Minnesota with Dr. Jaime F. Modiano, VMD, PhD, Aurora Kinase Inhibition in Osteosarcoma. For more information, please click here.

How you can help Osteosarcoma Research

Cryptorchidism and Male Infertility

Cryptorchidism is a congenital defect where one or both testes are not fully descended into the scrotum. Cryptorchidism has been attributed to increased risk of testicular cancer and infertility.

In 2006, the LHF provided funding to Texas A&M University to detail the gene content of the Y chromosome, and in particular the testis-specific genes that, when defective, may cause infertility. The final report on this work can be reviewed by clicking here.

In 2010, funding was provided to Iowa State University and Dr. Max Rothschild, PhD, for “Whole Genome Association Analyses for Cryptorchidism in Dogs.” Information on this study can be found by clicking here.

Addison’s Disease

Addison's Disease is a hormonal disorder that results in a decreased production of glucocorticoids and mineralocorticoids by the adrenal gland. These substances are responsible for a host of functions, including metabolism, electrolyte and water balance, and the ability of the body to deal with stress.

The Leonberger Health Foundation considers Addison’s our “first disease” and our first success! Addison’s was the first disease research the LHF sponsored in 2002 with subsequent funding of research in 2004 to both the University of California, Davis, and the University of Michigan. Final summaries of the research can be found clicking here for University of California Davis or here for the University of Michigan.

Although the exact genetic cause has yet to be found for Addison’s, understanding of the heritable traits of the disease has allowed the LHF to work with the breeder community to reduce the number of Addison’s cases significantly, and virtually eliminate the disease from the Leonberger population.

What can we help you find?