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Research Updates

Dr. Ned Patterson Updates - July 2013    March 2013    Dec 2012    Sept 2012    Nov 2011    Sept 2011   Feb 2011    Dec 2010    Nov 2010   July 2010   July 2009   Dec 2008   Jan 2008
Dr. Karen Munana Updates - Feb 2012   Sept 2011   Dec 2010   Oct 2010   June 2010   Feb 2010   Aug 2007
Dr. Hannes Lohi Updates - July 2011
Dr. Dawn Merton Boothe Updates - Sept 2012    Sept 2011    March 2011

July 2014

Toby’s Foundation to give $10,000 to support Epilepsy Research Initiative.
Toby's Foundation has been instrumental in raising canine epilepsy awareness by bringing much needed attention to this disease, educating the public about the disease, helping breeders and pet owners and sponsoring research grants to find the genes responsible for canine epilepsy and for more effective treatments for dogs suffering from this disease. Epilepsy is one of the most common neurological diseases affecting dogs. In keeping with our commitment to stopping this disease and improving the quality of life for dogs suffering from epilepsy. Toby's Foundation will give $10,000 to support the Canine Health Foundation’s Epilepsy Research Initiative. Please continue to help us by making a donation to Toby’s Foundation.

July 2013

Research News for Dr. Ned Patterson

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!

March 2013

Research News for Dr. Ned Patterson

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 website 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.

December 2012

Research News for Dr. Ned Patterson

Three chromosome areas have been identified that may be related to contributing to epilepsy in the Australian Shepherd breed. Please visit the Research page on our website to read the latest research news. 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 visit our website and/or 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."

      

Single Dose Extended Release Anticonvulsant Shows Promise

Dr. Dawn Merton Boothe at Auburn University has completed her work evaluating extended release Keppra, and the results look promising!

From Morris Animal Foundation: "Thank you and everyone involved with Toby's Foundation for your generosity and support of Morris Animal Foundation's commitment to creating a better and healthier tomorrow for animals. Because of the kindness of friends like you, the Foundation has been able to fund tremendous health breakthroughs for all animals, including dogs."

"Toby's Foundation is a generous study co-sponsor of Dr. Boothe's study Pharmacokinetics of Single Oral Dose Levetiracetam Extended Release Tablets in Healthy Adult Dogs(D10CA-060)."

 

"Pharmacokinetics of Single Oral Dose Levetiracetam Extended Release Tablets in Healthy Adult Dogs Dawn Merton Boothe, DVM, PhD D10CA-060"

"Results: Single Dose Extended Release Anticonvulsant Shows Promise Epilepsy is a serious, late-onset seizure disorder that affects a large number of breeds and usually requires lifelong treatment. Dogs often 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. Researchers, funded by Morris Animal Foundation, studied the effectiveness in dogs of a new extended-release Keppra product that was recently approved for human-use. They found that the extended-release version levetiracetam is a safe, convenient anticonvulsant drug that can be given to dogs in a single oral dose with a longer half-life. These data suggest that the new product would be a better treatment option and would provide better long-term management of seizures in dogs with epilepsy."

February 2012

Toby's Foundation's grant for Dr. Karen Munana at NCSU for the project "The Pharmacokinetics of Levetiracetam in Epileptic Dogs When Used Concurrently with Other Antiepileptics" has concluded.

"This study was undertaken to determine whether the metabolism of the anti-seizure drug levetiracetam (LEV) varies depending on whether it is given in combination with phenobarbital and/or potassium bromide to dogs with epilepsy. Dogs previously diagnosed with epilepsy that were being treated with LEV in addition to phenobarbital, potassium bromide or both were studied. Blood samples were collected at 5 time points within a 6-hour period for measurement of LEV levels. The study demonstrated that there is considerable variability in blood levels of LEV among dogs that are receiving LEV as a treatment for epilepsy. The group of dogs being administered LEV and bromide in combination tended to have the highest blood LEV levels, followed by the group receiving LEV and phenobarbital in combination, while the group receiving LEV, phenobarbital and bromide in combination tended to have the lowest blood LEV levels. This suggests that the administration of phenobarbital, with or without bromide, might affect the metabolism of LEV when the drugs are used together to treat epilepsy in dogs. Based on the study results, it is recommended that LEV blood levels be measured in dogs that are receiving LEV in combination with other drugs, particularly if adequate seizure control is not achieved. Additional studies are required to determine a recommended target LEV range in dogs that is associated with seizure control."

This study can advance more effective treatments for dogs suffering from canine epilepsy. There is more detailed information that will become available after the study is published.

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.

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.


Toby's Foundation is co-sponsoring a Morris Animal Foundation (MAF) study for Dr. Dawn Merton Boothe at Auburn University.

'This study suggests that extended release levetiracetam (commercially known as Keppra) would be a better treatment option for dogs with epilepsy''. Please see below.

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.'

 

North Carolina State University has a survey they would like filled out by owners of pets with epilepsy on 'The Impact of Epilepsy in Companion Animal Patients' Please see below.
 

'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:

http://harvest.cals.ncsu.edu/surveybuilder/form.cfm?testid=12936

 

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

July, 2011

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.

In collaboration with Dr. Ned Patterson and his team from the University of Minnesota who recently mapped the first epilepsy (IE) locus in the Australian Shepherd (AS), Dr. Hannes Lohi will utilize the latest next - generation sequencing approaches to identify the gene(s) causing or contributing to epilepsy in the AS. The latest next-generation sequencing recently became available and is already being used in Finland. Dr Lohi will sequence genes in the area of the Chromosome that Dr. Ned Patterson and his team recently got the significant hit on. Dr. Lohi says that "identification of the epilepsy-causing mutations would enable us to develop genetic tests for AS for breeding purposes. It would also improve our understanding of the pathogenesis of the disease, and provide a novel candidate gene for other IE breeds and as well human IEs."

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.

Our 7th Anniversary is fast approaching and our anniversary theme is "Let's Keep the Ball Rolling" for Aussie epilepsy research and that is precisely what we are doing by sponsoring a TF grant for Dr. Lohi. Please see our current ad.

Progress is being made and outstanding research is being done. We appreciate the commitment and dedication of Drs. Patterson and Lohi and their research groups to canine epilepsy research and to the Australian Shepherd. Please continue to help us support the research to find the causative genes and develop a screening test by making a donation today. Your help is needed. Your donation is tax deductible to the fullest extent allowed by law.

If you haven't already, please donate a blood sample today to Dr. Ned Patterson's Aussie epilepsy research at the University of Minnesota on your affected dog and your dog 10 + years old that have never had a seizure.
 

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.'

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

December, 2010

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
North Carolina State University
College of Veterinary Medicine
Department of Clinical Sciences
4700 Hillsborough Street
Raleigh, NC 27606
919-513-6812 Phone
919-513-6830 FAX

Update from Dr. Patterson

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.'

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.

October, 2010

Toby's Foundation Awards its First direct Grant to Dr Karen Munana at North Carolina State University and Dedicates it in Memory of Sheila Dolan
Pam Douglas, President of Toby's Foundation says 'we can now sponsor grants under $10,000 for canine epilepsy research. This is an important step for us in the fight against canine epilepsy. Our mission is to stop canine epilepsy by supporting research to find the gene(s) responsible and develop a screening test and to support research for more effective treatments for dogs affected by this disease.

Dr. Munana's grant is for one year and will investigate 'The Pharmacokinetics of Levetiracetam in Epileptic Dogs When Used Concurrently With other Antiepileptics'. The award is for $5,276.00. For larger grants we can continue to co-sponsor studies such as the one we currently have with the Canine Health Foundation (CHF) for Dr. Ned Patterson's Aussie epilepsy study at UMN, Grant #748 'SNP Association Mapping for Canine Epilepsy'.

 

ImageDr. Munana presented two studies at the American College of Veterinarians in Internal Medicine (ACVIM) in June 2010 in Anaheim, CA . Please click on the link below to go to our Research page and read summaries from Dr. Munana on these two studies regarding more effective treatments for dogs affected by canine epilepsy. It is estimated that as many as 25% of the dogs affected with the disease have refractory seizures meaning they do not respond well to traditional treatments and their seizures are not well controlled.

Pam Douglas met with Dr. Karen Munana at the ACVIM meeting in Anaheim , CA to discuss with her about our newly awarded grant for her research and her two preceding studies. Pam Douglas also met with Dr. Ned Patterson of UMN at the ACVIM meeting to discuss Aussie canine epilepsy research and a new grant in 2011 to keep Aussie epilepsy research moving forward.

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.

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. Mu'ana, North Carolina State University College of Veterinary Medicine
Funding:  Morris Animal Foundation
 

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. Mu'ana, North Carolina State University College of Veterinary Medicine
Funding:  Collie Health Foundation

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

Pamela Douglas, President of Toby's Foundation represented canine epilepsy at the AES conference in Boston, MA in December 2009 shortly after Toby's death due to this disease. The AES annual meeting attracted some 4.000 participants from around the globe. The Society promotes research and education for professionals dedicated to the prevention, treatment and cure of epilepsy. Even though there were only a few of us present for canine epilepsy, this was a very important meeting to attend for anyone interested in epilepsy'as Dr. Patterson said to me 'Same disease different species'. December 2009 032 3
December 2009 020 4

Pamela Douglas met with Dr. Ned Patterson of UMIN at the AES meeting. Dr. Patterson is the principal investigator on the Canine Health Foundation grant that Toby's Foundation co-sponsors for the Australian Shepherd. Pam Douglas and Dr. Patterson discussed epilepsy research in general and Aussie research in particular. More Aussie samples will be analyzed in the coming months using a more powerful SNP array that recently became available.

 

 

The conference also provided the opportunity to meet with world renowned researcher and geneticist Dr. Hannes Lohi from Finland who is also working on the Aussie along with other breeds and is collaborating with Dr. Patterson. This was our first meeting with Dr. Lohi and it was a great opportunity to speak with him in person. Dr. Lohi discussed the research he is doing on the Aussie and 15 other breeds.

Drs. Lohi and Patterson were at the meeting to present their study, 'Genetic Analyses in Different Breeds Identifies a Novel Mutation and Several New Loci in Canine Focal Idiopathic Epilepsies' by Drs. Lohi and Patterson et al. It had been accepted by AES for exhibit in the poster session. With respect to Dr. Lohi's presentation on more than 15 breeds at the AES meeting Dr. Patterson stated in a recent report that 'it is clear there are a limited number of breeds where one gene may cause epilepsy, but in most breeds the genetic predisposition is influenced by more than one gene which is very likely to be the case for Aussies.'

February, 2010

Recruiting Dogs for New Anticonvulsant Research
Julie Nettifee Osborne from North Carolina State University tells us that' a new anticonvulsant has been developed by a major veterinary pharmaceutical company. 

'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:

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!

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.'

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.

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.

January, 2008

AKC Canine Health Foundation Announced Funding for Epilepsy Study for the Australian Shepherd and the English Springer Spaniel

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.

August, 2007

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,
Julie Nettifee Osborne, RVT, BS
NCSU-CVM

December, 2006

President of Toby's Foundation attends akc/CHF Fundraiser
Pamela Douglas, President of Toby's Foundation and CA Sharp, President of ASHGI, attended the sixth annual AKC/Canine Health Foundation Gala by the Bay held at the Hyatt Regency Hotel, Long Beach on December 1, 2006. This event raises funds to find cures for canince health issues.


Left to Right: CA Sharp, Erika Werne, Director, Canine Research & Education, and Pamela Douglas

November, 2006 - Toby's Foundation Completes Pledge for Research
Toby's Foundation is pleased to announce completion of its $5,000.00 pledge. Thank you to everyone who helped us reach this goal. We will, of course, not stop here. We will continue to raise funds for the research to help stop canine epilepsy. The funds have been placed in a Donor Advised Fund for Aussie Epilepsy Research at the Canine Health Foundation and can be matched by them.

April, 2006 - For Immediate Release from Pam Douglas, President Toby's Foundation
As we approach the second anniversary of Toby's Foundation, I have some very exciting news to share with you about the latest developments in the Aussie epilepsy research. We have gone from less than 100 blood samples just three years ago to over 1000 Aussie samples in the database as of April 2006 as reported at the USASA Nationals in MO! We have more samples in than any other breed! We are a committed group of Aussie breeders, fanciers and pet owners and the researchers have taken notice! The researchers have identified two Aussie family groups they can begin to work with. If we support the research now by filling in the missing links in family groups, raising the necessary funds for the Aussie research, submitting blood samples and if it turns out to be a simple recessive gene (which is how it now appears than the researchers), we may have a screening test in as little as 12-24 months. Otherwise, it will take longer. We have never been so close!  As C.A. Sharp who attended the USASA Nationals said "We can see the light at the end of the tunnel!" We are very optimistic.

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.

Please consider making a donation for Aussie Research.  
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!

Please click here to see the action items necessary to support our researchers with samples and more information.

October, 2005 - Pamela Douglas attended the ASCA Nationals.
We attended a seminar by Liz Hansen during nationals that gave an epilepsy research update. The good news'there are over 700 Aussies sampled as of October 2005! The bad news'there are a lot of 'holes' in families.

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. 

We are asking the owners of the 92 affected dogs to join us in making sure that all of the dogs (both affected and unaffected siblings, parents, grandparents, and offspring) related to your dog submit a blood sample to the University of Missouri. It is very important that we have complete family information from all affected dogs and their relatives.
Please do everything you can to get the samples submitted from all of your dog's relatives.

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