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Research UpdatesDr. Ned Patterson Updates -
Sept 2012
Nov 2011
Sept 2011
Feb 2011
Dec 2010
Nov 2010
July 2010
July 2009
Dec 2008
Jan 2008 September 2012
February 2012
November, 2011
“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.”
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. September, 2011 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.
D10CA-060: Pharmacokinetics of Single Oral Dose Levetiracetam Extended Release Tablets in Healthy Adult Dogs, Dawn Merton Boothe, DVM, PhD
“PROGRESS UPDATE: Epilepsy is a serious, late-onset seizure disorder that affects a large number of dog breeds. Dogs often require lifelong treatment and frequently develop a tolerance to therapy, so increasingly higher doses of anticonvulsants are needed. Previous studies showed that levetiracetam (commercially known as Keppra), a human antiepileptic drug, is well tolerated by dogs, even at concentrations that exceed the maximum therapeutic range for humans. The drug also shows promise in controlling seizures. However, the half-life of levetiracetam is short in dogs. To address this issue, researchers at Auburn University are studying a new extended-release Keppra product, approved for humans, that may allow for twice- or once-daily dosing in dogs. To date, researchers have completed all data collection from client-owned dogs and are in the process of conducting statistical analysis. Preliminary analysis suggests that the new extended-release Keppra product results in drug concentrations that stay above the minimum recommended therapeutic dose for 18 hours (compared to only 6 hours following intravenous administration). This study suggests that extended-release levetiracetam would be a better treatment option for dogs with epilepsy than regular-release levetiracetam, and it should be used in any further clinical trials studying the efficacy of levetiracetam for long-term management of seizures in dogs with epilepsy.”
“Dear Pet Owner:
Seizures affect more than 5 percent of the companion animal population. We are contacting you today to see if you might be willing to share with us some information regarding your experiences with a pet with epilepsy so that we, as the veterinary profession, can develop a greater understanding of your needs living with a pet with epilepsy. Information obtained from this survey will help us to: Increase our understanding of the disease impacts, help us to provide more information to potential grantors to study the disease as it relates to impacts on the owner, and more.
All of the personal information provided will
remain confidential. We appreciate your consideration of this request. The
survey can be accessed at the followiing URL:
If you have any questions whatsoever regarding this survey, please contact Julie Nettifee Osborne, RVT, BS, VTS (Neurology) julie_osborne@ncsu.edu or 919-513-6812.”
Warm Regards,
Julie Julie Ann Nettifee Osborne, RVT, BS North Carolina State University College of Veterinary Medicine Department of Clinical Sciences 1060 William Moore Drive Raleigh, NC 27607 919-513-6812 Phone 919-513-6830 FAX http://cvm.ncsu.edu/epilepsyresearch/bio-julie.html Toby's Foundation (TF) is proudly sponsoring a grant entitled "Identification
of Epilepsy-Causing Mutations in Australian Shepherds" for Dr. Hannes Lohi and
his research group at the University of Helsinki, Finland for one year for
$10,000, Toby's Foundation, TF Grant Number 5-2011. We are very excited about our grant which will help Aussie epilepsy research
continue to move forward using the latest technology while Dr. Patterson applies
for his next CHF grant. We stand ready with your help to co-sponsor that grant. March, 2011 Morris Animal Foundation (MAF) Grant
We are pleased to announce that we are co-sponsoring for $3,000 a Morris Animal Foundation (MAF) grant, "Evaluating the Safety and Efficacy of a Drug to Control Epilepsy in Dogs" for Dr. Dawn Merton Boothe at Auburn University for one year. This study will determine the efficacy of levetiracetam (commercially known as Keppra) as a safe, convenient anticonvulsant drug that can be given to dogs in a single oral dose, allowing its use as a sole anticonvulsant drug for canine epilepsy patients.
Because of the generosity of donors and some corporate matching gifts we are able to help sponsor research for more effective treatments for dogs suffering from canine epilepsy while we continue to support research to find causative genes for canine epilepsy and develop a genetic test. February 17, 2011 Researchers Get First Significant Hit On The Australian Shepherd 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.” 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. A few more dogs with epilepsy are needed for a new study. Can you help? For information on this new study and contact information to see if your dog can help by participating please see below. All blood levels will be provided to the owners at no charge. Dogs would not necessarily have to go to NCSU-CVM, as long as the referring DVM is willing to help obtain samples. NEW!! Canine Keppra Pharmacokinetic Study III: Recruiting Open, July 2010 Recruitment is open for dogs with epilepsy that are being treated with Keppra (levetiracetam) and Phenobarbital (group I) Keppra and Potassium Bromide (group II) , or Keppra, Phenobarbital and Potassium Bromide (group III) for a Pharmacokinetic study. This study is being conducted at North Carolina State Unversity-College of Veterinary Medicine, under the direction of Dr. Karen Munana, DVM, DACVIM (Neurology). If your dog has been diagnosed with epilepsy, and is receiving the drugs listed above in any of the 3 groups listed, we are interested in sampling your pet to determine how Keppra interacts with the other anticonvulsants through sequential blood sampling in a one-day study. All blood levels will be provided to the owners at no-charge. If you are interested in more information regarding this project, or to see if your pet qualifies, please contact Julie Osborne, julie_osborne@ncsu.edu or 919-513-6812. We would like to thank Toby's Foundation for their assistance in the funding of this important project.
Julie Nettifee Osborne,
RVT, BS 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. 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 www.tobysfoundation.org/samples.htm and www.tobysfoundation.org/Donors.htm.
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. June, 2010 Research Updates from Dr. Karen Munana Dr. Karen Munana presented her finding on the two studies EVALUATION OF LEVETIRACETAM AS ADJUNCTIVE TREATMENT FOR CANINE EPILEPSY and ASSOCIATION BETWEEN THE ABCB-1 (MDR-1) GENE AND SEIZURE CONTROL IN CANINE EPILEPSY at the American College meeting in Anaheim, CA on June 12, 2010. Below are the summaries from her findings. EVALUATION OF LEVETIRACETAM AS ADJUNCTIVE TREATMENT FOR CANINE EPILEPSY
Principal Investigator: Dr. Karen R. Muñana, North Carolina State University
College of Veterinary Medicine The purpose of this blinded, placebo controlled clinical trial was to evaluate the safety and effectiveness of levetiracetam when used as add-on therapy in dogs with poorly controlled idiopathic epilepsy. Findings from the study suggest that levetiracetam is safe in epileptic dogs. There was no difference in incidence of side effects between levetiracetam and placebo treatment, and no changes in laboratory parameters were identified throughout the course of the study. The majority of dogs experienced a decrease in seizure frequency during levetiracetam treatment. However, the weekly seizure frequency relative to baseline decreased during both levetiracetam and placebo administration, such that a significant difference in effectiveness of levetiracetam over placebo was not observed. Levetiracetam serum levels were highly variable and did not correlate with treatment response. Further evaluation of levetiracetam as therapy for canine epilepsy is warranted. ASSOCIATION BETWEEN THE ABCB-1 (MDR-1) GENE AND SEIZURE CONTROL IN CANINE EPILEPSY.
Principal
Investigator: Dr. Karen R. Muñana, North Carolina State University College of
Veterinary Medicine Medically refractory seizures are a significant problem in both human and canine epilepsy. Alterations in the ABCB-1 (also known as the multidrug resistance or MDR-1) gene have been proposed to play a role in drug-resistant epilepsy. The ABCB-1 mutation results in loss of function of p-glycoprotein, a protein responsible for pumping compounds out of the brain. The aim of this study was to determine whether differences in the ABCB-1 gene are associated with seizure control in canine epilepsy. Collies, a breed known to have a high incidence of mutation of the ABCB-1 gene, were studied. Epileptic dogs with the mutation were significantly more likely to have good seizure control and to be treated with fewer antiepileptic medications than epileptic dogs that were carriers of the mutation or that had the normal genotype. These findings suggest that p-glycoprotein may influence seizure severity in epileptic dogs. Further study is needed to determine whether this is a manifestation of the initial seizure disorder or reflects a response to treatment. For further information, please contact animalepilepsy@ncsu.edu.
Toby’s Foundation attended the 63rd Annual Meeting of the American Epilepsy Society
February, 2010
Recruiting Dogs for
New Anticonvulsant Research “We are recruiting dogs that are not on any anticonvulsants at this time. Feel free to post the following link on your website, www.helpfordogswithseizures.com The study is nationwide and selection criteria and study information are listed on this link. As for the Keppra study and the MDR study, they have both been completed, and we are in the process of writing up the results for presentation at the ACVIM forum in June. According to Dr. Munana, we should be able to share the results with them within the next few months, and would appreciate them posting the information on their website. Other studies that are underway include a clinical study of Keppra Pharmacokinetics when given in combination with Phenobarbital. We actually still need a few dogs to participate that are on Phenobarbital at steady state levels, and Keppra. They do not have to come to NCSU-CVM, we can potentially arrange for sampling to be done and shipped to us from a referring DVM or Neurologist”... November, 2009 We have received Dr. Ned Patterson’s current progress
report on the research. Some exciting highlights are: 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.
Dr. Patterson at UMN, Dr. Johnson at UMO, and Dr. Lohi
in Finland continue their efforts to find the genes responsible for canine
epilepsy. 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. 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. 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. December, 2007 Blood Sample Submission Updates 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! December, 2007 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! October, 2007 Blood Sample Submission Updates 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. September, 2007 Pamela Douglas, J.D., President of Toby's Foundation, Inc. attended the biennial 2007 Tufts' Canine and Feline Breeding and Genetics Conference with a Special Focus on Canine Epilepsy in Sturbridge, MA on September 13th and 14th. Please see her report for the most current information on the status of canine epilepsy research. North Carolina State University has sent us the following information regarding their epilepsy research. Click here to read the full press release. Pamela: I have attached some information that you may include on your website or in newsletters, but in short, we are recruiting for the following: 1. Collies, Shelties and Australian Shepherds for the MDR-1 study (click here for specifics). As long as pet owners are able to provide a copy of a recent anticonvulsant level that is in therapeutic range, we will send them brushes for MDR testing that will be performed at no cost to the owner. Results of the testing will be provided to each owner. 2. Dogs with Refractory Epilepsy (At least 4 seizures/month) are being recruited for an extension of the Keppra Drug study. Dogs for this study will have to travel to NCSU-CVM or the University of Tennessee approximately 7-8 times over a 44-week period. For information regarding the above 2 studies, contact julie_osborne@ncsu.edu . 3. Blood samples from epileptic dogs are still being requested for a genetic study on canine epilepsy. For more information on this study contact carolinacanineepilepsy@gmail.com Thanks for all you do to help out pets and their owners!
Warm
Regards, December, 2006
November,
2006 -
Toby's Foundation Completes Pledge for Research April, 2006 - For
Immediate Release from Pam Douglas, President Toby's Foundation In addition, Toby’s Foundation has joined forces with the United States Australian Shepherd Foundation (USASF) and the Australian Shepherd Health and Genetics Institute (ASHGI) to raise $70,00.00 for Aussie epilepsy research. Toby’s Foundation pledged $5,000.00 to this joint effort. The funds will go to the Canine Health Foundation (CHF) and be placed in a donor advised fund (DAF) designated for Aussie epilepsy research. UMO is applying to CHF for grants and Erika Werne, Director of Canine Research and Education at CHF has told us that she will need the support of the Aussie community to raise some of the necessary funds to qualify for matching funds. Our $5,000.00 pledge will then become $10,000.00 as they match it dollar for dollar. Our joint ad with ASHGI and USASF will be out in the May/June 2006 issue of Aussie Times and the AS Journal. All funds received as such will be sent to a Donor Advised Fund (DAF) at the Canine Health Foundation (CHF). Please help us raise the necessary funds for this vital research. While we have accomplished a lot there is still a lot to be done. With your support we shall be able to continue our work to defeat canine epilepsy. We have no time to waste. We must not lose our present momentum! We must stay on track!Thank You! October, 2005 -
Pamela Douglas attended the ASCA Nationals. 92 of the samples
are from affected dogs. Toby is one of the 92 affected
dogs, but because of confidentiality, we don’t know the
identity of the others. | |||||||||||||||||||
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