Research Updates
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Research Update for Toby's Foundation co-sponsored CHF Grant:
Canine Epilepsy: Genetic Variants, Biomarkers, and New Therapies
Dr. Ned E. Patterson, DVM PhD; University of Minnesota
December 2017
Our goal in these studies are to: 1. identify genetic (DNA) mutations associated with epilepsy and/or drug resistant epilepsy in Australian Shepherds,and Vizslas; 2. To see if blood micro RNA (miRNA) levels vary within epilepsy dogs and could be used as markers of predisposition to epilepsy and/or response to therapy; 3. To see if novel IV drugs (topiramate or allopregnanolone) might be effective for treatment of seizure emergencies in dogs (and people)...we have found some chromosomal areas that may contain and epilepsy genes or genes for being less responsive to drug therapy for each breed, but as epilepsy is polygenic in both breeds with likely a number of related genes in each breed, we have not yet identified a marker or area that clearly stands out for a confirmed epilepsy gene. We will continue our studies in these breeds in the future as genetic technologies have new ways of analysis and we collect more DNA samples from each breed. We have successfully measured miRNA levels and are in the process of final analysis looking for any patterns and associations for possible future use of blood miRNA as a diagnostic marker or marker of how severe epilepsy is in an epileptic dog and/or how well therapy is working in epileptic dogs. In the IV drug studies for new emergency drugs for life-threatening seizures we have completed all of our IV topiramate studies and we have a paper that has just been published in December 2016. The conclusion is that IV topiramate appears to be safe and potentially effective in this pilot study of 5 dogs, and also gives information that IV topiramate might also be safe and effective for people since dog epilepsy and seizure emergencies are so similar to that in humans. This means IV topiramate could be used for possible future studies in veterinary (and human) emergency rooms for the treatment of seizure emergencies. We have just completed a similar study for IV allopregnanolone and initial results indicate it also is likely safe and effective, and with internal funds we are testing one more dosage for it and when completed will submit a paper for publication.
August 2016
Dr. Patterson and his team are working on identifying genetic (DNA) mutations associated with epilepsy and/or drug resistant epilepsy in Australian shepherds, and Vizslas.
The researchers have DNA for affected and unaffected Australian shepherds and Viszlas. In initial analysis of 170,000 single nucleotide – SNP (DNA) markers in a portion of the affected and unaffected dogs, the researchers have found possible areas for epilepsy genes in Australian shepherds and in Vizslas. For both breeds they will do additional SNP markers with 4 times as many SNP markers, and additional sequencing of genes in possible areas. They are looking for a causative DNA mutation to develop genetic screening tests.
The researchers are also working to see if blood micro RNA (miRNA) levels vary within epilepsy dogs and could be used as markers. The researchers have successfully measured miRNA levels and are looking for any patterns and associations for possible future use of blood miRNA as a diagnostic marker or marker of how well therapy is working in epileptic dogs.
March 2013
From Dr. Ned Patterson's End Year 1 progress report for CHF grant #01615: Identification of Idiopathic Epilepsy Genes in Australian Shepherds that Toby's Foundation co-sponsors.
We are continuing in depth analysis, and working on finding the most likely genes in each area of three chromosomes that may be related to contributing to epilepsy, and we plan to find additional markers near the genes. Currently we are in the middle of sequencing two candidate genes from these three identified areas. In addition, we plan to utilize next generation sequencing to sequence portions of these 3 chromosomal areas in the next 6-9 months, if needed, in our search for genetic mutations contributing to epilepsy in Australian Shepherds.
We need your help! New blood samples from affected dogs are needed. Please send in a blood sample from your dog with idiopathic/primary epilepsy for Dr. Ned Patterson's Aussie epilepsy research at the University of Minnesota. New samples from dogs that are 10+ years old that have never had a seizure are also needed to serve as controls.
To submit a blood sample from your dog please go to our Blood Samples page and click on the link for the University of Minnesota for all the information, instructions and forms that you will need to submit a blood sample. Your information is kept confidential.
July 2013
Dr. Ned E. Patterson of the University of Minnesota has been given a one year extension for CHF Grant 01615: Identification of Idiopathic Epilepsy Genes in Australian Shepherds. The grant is now extended to December 31, 2014.
Dr. Patterson's mid-year 2 report states, once we identify a confirmed mutation we will then develop a DNA based genetic test. Dr. Patterson has obtained new cases and new controls and plans to analyze these new DNA samples with complete standard genetic analysis with the latest SNP chips. In addition we continue to analyze the 3 identified areas for more markers and possible mutations.
Researchers have made progress let's keep the momentum going!
The researchers are continuing in-depth analysis to find the genetic mutations contributing to epilepsy in Australian Shepherds in three chromosome areas that have been identified.
We need your help! New blood samples from affected dogs are needed. Please send in a blood sample from your dog with idiopathic/primary epilepsy for Dr. Ned Patterson's Aussie Epilepsy research at the University of Minnesota. Please see the information below to submit a blood sample from your dog.
Please make a donation today to Toby's Foundation to help us in the fight against canine epilepsy. Your donations are needed and are tax deductible to the fullest extent of the law. Please see the information below to make a donation online or by mail. Thank you!
December 2012
Three chromosome areas have been identified that may be related to contributing to epilepsy in the Australian Shepherd breed. The researchers are working to find the gene(s) causing or contributing to epilepsy in the Australian Shepherd so a screening test can be developed.
If you haven't already please send in a blood sample on your dog for Dr. Ned Patterson's Aussie epilepsy research study at the University of Minnesota to help us in the fight against canine epilepsy. Please see the information below. Blood samples from affected dogs are particularly needed. If you have any questions please email us.
September 2012
Three Chromosome Areas have been identified that may be related to contributing to epilepsy in the Australian Shepherd Breed
As you may recall, Dr. Ned Patterson and his team at the University of Minnesota in 2010-2011 performed a Genome Wide Association Scan (GWAS) with genetic markers for Idiopathic Epilepsy (IE) in 19 affected and 21 unaffected Australian shepherd (AS) dogs, and found a chromosomal region with a statistically significant association indicating that there is very likely to be a nearby genetic mutation related to epilepsy in Aussies.
Below is the latest research news from Dr. Patterson's 1st progress report for his Canine Health Foundation (CHF) grant, Identification of Idiopathic Epilepsy Genes in Australian Shepherds, that began January 1, 2012 and ends December 31, 2013. We are co-sponsoring this grant with $25,000 thanks to your generosity, support and help in the fight against canine epilepsy.
Genetic marker data from 88 Australian Shepherds (44 cases and 44controls) total has now been analyzed with standard genetic association statistical analysis. This includes 25 new cases and 23 new controls during this grant period. So far there are two different chromosomes that continue to potentially contain an associated epilepsy gene or genes. We have identified and a new third potential area in the last 6 months.
We are continuing with additional in depth analysis, and working on finding the most likely genes in each area of each these 3 chromosomes that may be related to contributing to epilepsy, and we plan to find additional markers near candidate genes and/or sequence one or more candidate genes in the next 6-9 months. In addition we plan to utilize next generation DNA sequencing to sequence large portions of some of these 3 chromosomal areas in the next 6-9 months, if needed, in our search for genetic mutations contributing to epilepsy in Australian Shepherds.
September 2011
The Canine Health Foundation Board of Directors has approved Dr. Patterson's project for Identification of idiopathic Epilepsy Genes in Australian Shepherds to continue his epilepsy research.
This new CHF study is exciting news. As we reported earlier Dr. Patterson and his team got a significant hit on one chromosome in the Australian Shepherd. We appreciate the Canine Health Foundation's commitment to funding research to help improve the lives of all dogs and for funding Dr. Patterson's epilepsy study for Australian Shepherds. Toby's Foundation will support this study for Aussie epilepsy research by becoming a sponsor to help fund it.
November 2011
The CHF grant, Identification of Idiopathic Epilepsy Genes in Australian Shepherds, for Dr. Ned E. Patterson, DVM PhD, University of Minnesota, should begin by January 1, 2012. The amount of this grant is $106,289.
Information about Dr. Patterson's new CHF grant to continue his canine epilepsy research on the Australian Shepherd:
In 2010-2011 we performed a Genome Wide Association Scan (GWAS) with genetic markers for Idiopathic Epilepsy (IE) and found a chromosomal region with a statistically significant association. This indicates that there is very likely to be a nearby genetic mutation related to epilepsy in Aussies. Another chromosomal region is close to achieving significant association. In this ongoing study, we plan to sequence the small chromosomal area in the area of significance to identify the gene that is causing or contributing to IE in Aussies, as well as perform an additional GWAS The additional GWAS is needed to see if there is more than one gene contributing to the development of IE in AS. Once we identify a confirmed mutation we will then develop a DNA based genetic test. An IE genetic test would greatly assist breeding programs to identify affected puppies before they are sold by breeders and aid veterinarians in diagnosis and possibly treatment of affected dogs. It could also lead to the eventual elimination of this disease from the AS breed through selective breeding. In addition, once we identify one or more IE gene(s) in AS we will test to see if these mutation(s) affect other dog breeds with a high incidence of IE.
Toby's Foundation will cosponsor this grant:
Please help us support this research by making a Year End donation for 2011 to Toby's Foundation. All gifts are tax deductible to the fullest extent of the law.
Matching gifts have been very helpful in enabling us to sponsor canine epilepsy research. We have, to date, directly sponsored two grants and co-sponsored three other grants due to your generosity and matching gifts. If you have an employer with a matching gifts program please let us know and please make a donation to help us.
Researchers Get First Significant Hit On The Australian Shepherd
February 17, 2011
Dr. Edward (Ned) Patterson DVM, PhD, Dipl. ACVIM (SAIM) University of Minnesota College of Veterinary Medicine has announced some good initial news. In the last month we analyzed all of the data for the Aussies on the 170,000 marker chip and we did get a statistically significant hit on one chromosome. We are looking at what genes are in the area, and may sequence one or two. This is the only breed that we have yet gotten a significant hit for! This is fairly likely to be real but we will need additional dogs and analysis to confirm.
Pamela Douglas, President of Toby's Foundation says, this is really good news for our Aussies and certainly the most promising news we have received to date for our beloved Australian Shepherd. We are so pleased to learn that Aussies have their first statistically significant hit and are the only breed so far that the researchers have gotten such a hit on. Our efforts are paying off as we work to support the research. Let me emphasize that there is still much to be done. We need your help to continue to support the research by donating blood samples on your dogs and raising funds so we can see this through to finding the causative genes and developing a genetic test for Aussies!
Please donate a blood sample today to Dr. Ned Patterson's Aussie epilepsy study at the University of Minnesota on your affected dog and your dog 10+ years old that have never had a seizure. Also, please consider making a donation for epilepsy research.
"Today, February 17th, is Toby's birthday! He would have been 9 years old. How sweet it is that we get to announce some good news on his birthday! Thank you for your continued support." - Pam
July 2010
Dr. Patterson reports that during the past year 18 additional affected Aussies and 20 additional controls have been collected at University of Minnesota. They are continuing to try to collect more Aussie DNA samples to be sent to their lab in Minnesota for any needed future analysis and to verify the diagnosis whenever possible. The most important efforts will be to collect more samples of affected Aussies. They are analyzing the best 24 affected and 24 unaffected Aussies on the new more powerful SNP arrays during the next few months. Despite the complexity in Aussies they are committed to following through on the search for markers and genes in Aussies as long as funds and new DNA samples are available.
November 2010
Aussie Epilepsy Research Study
The Aussie Epilepsy Research study at the University of Minnesota has been extended to March 2011. Dr. Ned Patterson is running additional Aussies samples using more powerful SNP Chips. Blood samples from affected dogs are still needed. If you have a dog that has been diagnosed with idiopathic (primary) epilepsy please send in a blood sample from your dog. Blood samples from dogs 10+ years old that have never had a seizure are also needed to serve as controls. For information, instructions and forms to submit a blood sample and/or information to make a donation to support the research, please go to our Blood Samples and How Can I Help? pages.
December 2010
Dr. Patterson and his team have just completed whole genome SNP analysis on additional Aussie samples and will have the data fully analyzed in the next few months.
Dr. Patterson reports that If we get strong association for Aussies in the whole genome analysis with the 170,000 SNP array we would then work on fine mapping and developing a linkage test in this new CHF grant application in the Spring of 2011. If we do not yet find significant association, we would then work on continued collection of affected dogs and more whole genome analysis with the 170,000 array in this new grant application.
July 2009
Dr. Patterson at UMN, Dr. Johnson at UMO, and Dr. Lohi in Finland continue their efforts to find the genes responsible for canine epilepsy.
Dr. Patterson reports that additional Australian Shepherd cases and controls have been sent out for genotyping on the SNP arrays. This new data will be combined with the previous data and the analysis will then be revised. Drs. Patterson and Lohi will coordinate a concerted effort to analyze more Aussies in the next 6 to 9 months. Dr. Johnson at UMO is also in the midst of sequencing some interesting genes in a few of the possible areas of interest for the Aussies.
Dr. Patterson has also submitted additional ESS samples to his collaborators at the Mayo Clinic Shared Genotyping Resource. Our hope is that one or more areas with an epilepsy gene of influence will now become more apparent. Dr. Patterson recently had a chance to talk in detail in person with Dr. Hannes Lohi about all the Epilepsy projects with an emphasis on ESS, Aussies (and Vizslas).
It has become increasingly apparent that IE is likely to be polygenic in most breeds. To date, to our knowledge, no IE gene has yet been identified in any breed. Our, now formal, agreement with the U of MO and Finland allows us to compare possible chromosomal areas across breeds - ESS and Aussie's (also Vizlsas and other breeds) in case there is a shared gene across breeds in which putting the data together might be more efficient in identifying the specific gene.
November 2009
We have received Dr. Ned Patterson's current progress report on the research. Some exciting highlights are:
1. The two year grant that we provide financial support for and was due to end on March 30, 2010 will be extended an additional 6 months.
2. The researchers will analyze more Aussie samples using the new Illumina 150,000 - 200,000 SNP array. This new SNP array has just become available and has much more power than the previous SNP arrays.
3. Dr. Patterson is committed to continuing the search for markers and genes in Australian Shepherds as long as funds are available.
It is very important that we be ready to help provide the researchers with the funds necessary to enable them to continue this vital research to find the genes responsible for canine epilepsy and develop a screening test. We have assured Dr. Patterson that we are committed to continuing to raise funds and help collect blood samples for this important research and that we plan to increase our previous giving to support the research and do everything we can to assist him. We would like to at least double what we previously gave to support the research.
Dr. Patterson continues to work with Dr. Gary Johnson at the University of MO and Dr. Hannes Lohi in Helsinki, Finland. Dr. Patterson did have opportunity to meet with Prof. Lohi with an emphasis on the data in Aussies, ESS (and Vizslas). Their cooperative written agreement gives our Aussies and other breeds the best opportunity for a breakthrough and gives us the expertise and resources of each of these researchers.
Thank you for your help! We can't do it without you!
AKC Canine Health Foundation Announced Funding for Epilepsy Study for the Australian Shepherd and the English Springer Spaniel
January 2008
The AKC Canine Health Foundation announced the United States Australian Shepherd Association, United States Australian Shepherd Foundation, Australian Shepherd Health and Genetics Institute, Toby's Foundation and the English Springer Spaniel Field Trial Association Foundation all Partner to Contribute over $50,000 in Support. Click here to read the full press release.
June 2008
As we celebrate the 4th anniversary of Toby's Foundation, the timing and tools to find a gene marker for canine epilepsy have never been better! We are in a very good position with two outstanding researchers, Dr. Ned Patterson at the University of Minnesota and Dr. Hannes Lohi at the University of Helsinki, doing research on canine epilepsy in the Australian Shepherd to find the gene(s) responsible and develop a screening test.
Dr. Patterson and Dr. Lohi recently had the opportunity to meet for the first time in France in May. Dr. Patterson is coordinating with both Dr. Johnson and Dr. Lohi. In a progress report from Dr. Patterson, he said SNP Chip analysis has been completed on 30 affected and 30 unaffected Australian Shepherds by Dr. Hannes Lohi in Finland in collaboration with Dr. Gary Johnson at UMO-Columbia. Dr. Patterson at UMN is collaborating on statistical analysis of this data with them and is prepared to perform SNP chip genotypes and analysis on 20-30 additional affected and 20-30 additional unaffected Aussies in the next 6-9 months if significant association is not found and additional power is need for this breed. SNP markers are run by the Mayo Clinic in Rochester, MN who collaborate with Dr. Patterson.
December 2008
There is now a formal written agreement for the sharing of Australian Shepherd and English Springer Spaniel DNA samples and data between Dr. Gary Johnson at University of MO, Dr. Hannes Lohi in Finland and Dr. Ned Patterson at the University of Minnesota . Dr. Patterson has done an outstanding job for us in working to coordinate this effort.
What this news means to us is that there are officially three researchers and institutions sharing data about our beloved Aussie and looking at it independently to insure that nothing is missed or overlooked. It is not too long ago that we did not even have one researcher with a grant to look at the Aussie and now we have three! Dr. Patterson writes that all three institutions are separately analyzing all SNP data results in order to not miss any possible true areas containing an epilepsy gene(s). In addition the formal agreement will allow the researchers to compare chromosomal areas across breeds Aussie and ESS (also Vizlas and other breeds) in case there is a shared gene across breeds in which putting the data together might be more efficient in identifying the epilepsy gene.
Dr. Patterson reports that there are 3 chromosomal areas of mild association from the initial data for the Australian Shepherd but since the association is only mild 50 additional Australian Shepherd samples will be run using the SNP chip. It is hoped that this will confirm or exclude these three areas and find other areas of possible epilepsy gene(s). There is also one area of interest for the English Springer Spaniel that has been observed but this association is only mild so additional ESS samples, cases and controls, will need to be analyzed.
Toby's Foundation is dedicated to helping to stop one disease Canine Epilepsy. This is a disease whose time has come' to be eliminated! We will be here until The Australian Shepherd gets a screening test and every other breed that needs one does too.
Blood Sample Submission Updates
October 2007
Dr. Ned Patterson of the University of Minnesota College of Veterinary Medicine said at the Tufts Canine and Feline Breeding and Genetics conference To help these studies progress we encourage individuals to submit DNA of purebred dogs affected with epilepsy and their relatives to the various studies. In the case where more than one group is studying the same breed I recommend individuals submit samples to all groups performing the studies. Dr. Patterson said in notes from the Tufts Conference, there are a number of ongoing projects trying to determine the gene or genes that cause IE (Idiopathic Epilepsy) in various dog breeds at the University of Minnesota, the University of Missouri - Columbia, the University of California - Davis, the University of Toronto, the Animal Health Trust in England, A University in Finland, and at a few other institutions. Click here to see Toby's Foundation's recommendations for submitting your samples. The more researchers looking at the problem the better. Researchers can't look at a breed without samples. They would have to rely on the one study that has the samples to share them with others. Toby's Foundation will be putting out a list of research institutions that want samples for epilepsy research. We urge you to send samples from your dogs directly to 2 or 3 studies not just one.
We have been asked about CHIC. It is a repository not a study. CHIC has only been available for storage since 2006. It is a valuable resource that can ensure that samples are there for the future of your breed for research into many diseases including canine epilepsy. It certainly merits sending samples there.
We are in an exciting time now where several research institutions and studies either are or will be looking soon at canine epilepsy. We should support all the research that we can that is looking at the problem of canine epilepsy. This is a complex problem. The researchers were asked for their best estimate of how close we are to any breed getting the breakthrough. They said about 3-5 years unless we get lucky. Luck can happen and it recently did happen for the Aussie. Just ask Dr. Cathryn Mellersh who said at the Tufts conference that they got lucky Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd.
December 2007
We have added the Instructions information, the Dog Questionnaire and the Consent form for Dr. Patterson at the University of Minnesota . Dr. Patterson would like more samples from affected dogs, and their unaffected relatives (2 generations any direction), and also some older (6 years or older) unaffected and unrelated dogs. If you have already sent samples to Missouri, Dr. Patterson does have access to these samples. If you want to send a second sample to Dr. Patterson in Minnesota you can do so.
Among the things we learned at the Tufts conference focusing on canine epilepsy and bears repeating here are the more researchers looking at the problem the better and that ideally samples should be sent to all those who are working on canine epilepsy for the same breed. Please see our October 2007 research updates below in which we quote Dr. Patterson on this. If this is not possible you should at least send to one active study and CHIC. We have been recommending CHIC for all of 2007 (it was only set up in 2006). While CHIC is not per se a research study it is a very important repository to store samples for present and future use by researchers. By submitting samples to CHIC you insure that samples are there when needed for the future health of your dogs and your breed. Any researcher can apply to CHIC to use the samples and the samples can be used for any disease.
It is because we all did what was necessary to collect samples and raise funds that we were poised and ready and could in fact attract other researchers to take on the Australian Shepherd. Researchers need samples and funds for their work and the Aussie community was ready!
HARD WORK, PERSISTENCE AND DEDICATION IS PAYING OFF - WHAT A GIFT TO ALL OF US AT THIS CHRISTMAS AND HOLIDAY SEASON
TOBY'S FOUNDATION, INC. is contributing ten thousand dollars ($10,000.00) to help fund a very important and equally promising Australian Shepherd Research Project to develop a screening genetic marker test for canine epilepsy in the Australian Shepherd breed. The grant is co-sponsored by ASHGI, USASA, USASF and the Canine Health Foundation (CHF) who will match each dollar that our organizations contribute to the CHF grant for Dr. Ned Patterson at the University of Minnesota. The grant is for SNP Association Mapping for Canine Epilepsy. Dr. Ned Patterson (Principal Investigator) is an expert in the area of canine genetics and statistical analysis of pedigrees for heritable traits, and a clinician at the University of Minnesota Veterinary Medical Center. He will be responsible for the critical clinical diagnosis.
Dr. Pamela C. Douglas, President of Toby's Foundation said, This is something we have been vigorously working on since first making the contact with Dr. Patterson at the Tufts conference in September 2007. We learned there that the more researchers working on the problem the better. Dr. Patterson told me that he had just been approved for a SNP Association mapping grant for the English Springer spaniel and perhaps could add Aussies to it if the Canine Health Foundation (CHF) agreed and the wonderful news now is they have agreed! Fortunately, we were poised and ready because we had all done our work in collecting samples and raising funds. This is truly a united effort by the entire Australian Shepherd community. I am so pleased and grateful for the support that we have received from everyone. I want to mention here the Aussie breeders and owners in Finland who with only about 1500 Aussies in their country were able to collect approximately 300 samples for Dr. Lohi even before he received the 64 samples from UMO. This is truly a dedicated breed that we are proud to be a part of.
Dr. Patterson is an outstanding researcher who, as part of the consortium with UMO, has access to our Aussie samples. With SNPs now available to be used as genetic markers for mapping and two outstanding researchers, Dr. Patterson in Minnesota and Dr. Hannes Lohi in Finland working on the Australian Shepherd the time has never been better for this research. This is a two year grant. At this time we believe that more samples from affected dogs will be needed. We will let you know about this at a later time especially where and how to send them in.
Of course it is always sobering, Pamela Douglas said, to remember why we do this to think about all the dogs that have been hurt and have succumbed to this disease and still will for some years to come even after a screening test is developed but at least the day will come when no more dogs and the people who love them will have to go through this.
TOBY'S FOUNDATION is dedicated exclusively to stopping canine epilepsy!