PUG DOG ENCEPHALITIS (PDE)

March 2009
Report to Grant Sponsors (Pug Dog Club of America) from Dr. Kimberly Greer:

Statistical analyses were conducted on the set of Pugs with complete records (Fall ‘07), and included 2,875 females with 2,831 unaffected and 44 affected. There were 1,823 males with 1,809 unaffected and 14 affected. Of the Pugs with recorded coat color, there were both PDE affected and unaffected dogs included in the “fawn” group and in the “black” group with significantly more fawn dogs participating in the investigation. The median onset age of PDE is 19 months, with a range of 3 to 84 months (7 years). Median survival time is 23 days with an age of death, whether by euthanasia or natural death, ranging from 3 to 85 months.

The pedigrees for the 4986 Pugs have been entered into the dedicated database. Of the total dogs entered in this study, 51.1% were bred with an average inbreeding coefficient of 0.084, a value slightly higher than the predicted inbreeding coefficient for first cousin matings (0.0625), and slightly lower than the inbreeding coefficient for uncle-niece or aunt-nephew mating (0.125). This lack of random assortment in the Pug mating population expectedly yields increased homozygosity across the genome, pushing the proportion of potentially identical alleles beyond that predicted by Hardy-Weinberg equilibrium. Further demonstration of the high heritability of PDE is indicated by their heritability coefficient which is between 0.52 and 0.82, on a scale of 0.1 to 1.0. This analysis also reveals a significant association between the dogs’ gender, coat color, and disease heritability, clearly indicating that within this cohort, the majority of PDE affected dogs are fawn females while the least frequent combination of affected gender and color is black males.

Having shown that PDE is highly heritable, the definitive mode of transmission was the parameter of primary interest. The results revealed the potential for two or three significantly influential genes lending towards inheritance of PDE, or the potential for a primary locus with numerous modifier loci influencing PDE inheritance. The shift in statistical analyses slightly away from a single locus for inheritance may be due to the influence of environmental factors lending towards disease inheritance. To this end, PCR screening for herpes-, adeno-, and parvoviruses was completed. All of these tests proved negative on all included cases, arguing strongly against these viruses as environmental triggers for PDE.

The genome-wide scan was initially conducted on a subset of approximately 100 Pugs. We included an equal number of PDE affected and unaffected, unrelated Pugs. An initial overview scan revealed two markers which were significantly associated with the occurrence of PDE. A secondary analysis, utilizing a more dense population of markers, revealed that there is clearly a single point of significant association on a single canine chromosome. Although there is a genome-wide baseline association, most likely resulting from breed specificity, the region shows association significantly above the baseline. We have successfully identified one primary genotype segregating in the PDE affected dogs. This genotype is currently being explored and investigated in an extended sample of PDE affected and unaffected Pugs for verification and validation. Assuming that the genotype maintains its association with disease presentation, it will be a prime candidate for design of a genetic test.

There is some encouraging news there. No cure yet, but finding a genetic marker is going to be a HUGE thing.

Definitely. I was talking to Kyle about it last night as his area of expertise is gene therapy. He was trying to give me an explanation about genes and protein expression and it went over my head by I'm hoping to find a recent publication by Dr Greer that I can have him read and translate into something I can understand! The most recent publication is about a year old so that's likely the most recent one she has which wouldn't include this most recent grant data.

I'm both encouraged and worried that it appears to be heredity. Encouraged, of course, because if there is a genetic test, careful breeding and testing could make a big difference. My worry is that most people won't do these tests and careful breeding.

Interesting, thank you for sharing.

I had sent Dr. Greer an email letting her know about the forum and asking if there were any research updates I could share with our members. I received this today:

Amanda,
Thank you for your continued interest! I have moved the laboratory to Indiana, and would be most appreciative if you could post my newer contact information for your members. The address, office and email are below. My faculty page is: http://www.iue.edu/nsm/faculty/greer/ The faculty web pages are a work in progress, but the basics are there! I hope to have a full research site at: www.endpde.com very soon.

As for a research update, I am in the midst of submitting the most recent manuscript. It should be far enough through the process that I can give you a most up-to-date review in July. Please write me again with a reminder in July, and I can send you a sum of the work.

For the time being, I am still accepting Pugs into the study. Our AKC grant has been approved for the next year so the research can move along. Our cremation and shipping donation fund is drained, however. Since I am not allowed to use the AKC grant money for cremation or for sending Pugs to cremation, I must find donations to provide these services for the Pugs and their owners.

Basically, I am humbly asking Pug parents for donations to keep the PDE victims able to be involved in the studies. We all know that without having cremation and without the Pugs returning to their homes (where they belong!) with their owners, they cannot be a part of the ongoing research. The grant strictly prohibits payment of shipping the Pugs to the lab, cremation, or return shipment for them. Pug owners have graciously kept this rolling-fund (reserved for shipments and cremation of Pugs) just-filled-enough to keep the little guys "moving" for 6.5 years! Aren't Pug owners wonderful?! With the economy down, it's understandable that people are cutting back, but I must ask for people to remember the research if even just a little bit, so we can collectively help those who are currently suffering from PDE.

In the last two publications, which I will attach, we were able to show that the spinal tap does not reliably tell us whether a Pug has PDE or not. The spinal tap is no longer recommended for Pugs who are having encephalitis problems. We also know that the only medication helping the Pugs with PDE survive longer is the anticonvulsant. While many of them have prednisone and may also take other medications, it is the anti-seizure medication that is making the most difference for the Pugs with PDE. We have evaluated the seasonal effects and geographical effects as well, and neither of these are important for PDE. This means that no matter where you live or what type of climate you live in, it does not help or hurt your Pug in terms of getting PDE.

Thank you for the note, Amanda. I appreciate your organization of all the Pug parents. Please send my regards to all-
Kimberly

Kimberly A. Greer, Ph.D.
Assistant Professor
School of Natural Sciences and Mathematics
Indiana University East
2325 Chester Blvd.
Richmond, IN 47374
Office: 765-973-8445
Fax: 765-973-8430
kagreer@iue.edu

That's great to hear from her! Do you mind if I copy and paste all this to the PDE site?

How can I make a donation to her fund?

I made a donation last year to Texas A&M, I am wondering do we send donaitons now to Indiana Univ.?

Can I post this on my blog?

I've emailed her back to inquire about the best way to submit donations. As soon as I hear back, I'll share the information. I was also considering putting together some kind of collection as a group and just sending one big one to her. What do you think?

Go ahead and post her message on your sites, blogs, etc. I haven't attached the study reports and articles that she sent along with her email yet as I'm not sure I am permitted to do that.

BDazzpugs wrote:I made a donation last year to Texas A&M, I am wondering do we send donaitons now to Indiana Univ.?

Can I post this on my blog?

Definitely don't send anything to Texas any longer.

Amanda wrote:I've emailed her back to inquire about the best way to submit donations. As soon as I hear back, I'll share the information. I was also considering putting together some kind of collection as a group and just sending one big one to her. What do you think?

I think that's a great idea and I'd be willing to pitch in.

Amanda wrote:I've emailed her back to inquire about the best way to submit donations. As soon as I hear back, I'll share the information. I was also considering putting together some kind of collection as a group and just sending one big one to her. What do you think?

Go ahead and post her message on your sites, blogs, etc. I haven't attached the study reports and articles that she sent along with her email yet as I'm not sure I am permitted to do that.

A collection is a great idea. I'll also post this on the SNPR blog as well.

What is their website? I'd like to put the website and the little blurb on my blog too?

What if we sent a check to Amanda and Amanda sent one check on behalf of Pug Authority?

papaspugs wrote:What is their website? I'd like to put the website and the little blurb on my blog too?

What if we sent a check to Amanda and Amanda sent one check on behalf of Pug Authority?

The website is in the 1st paragraph of her email.

Very interesting about the spinal tap not being recommended anymore. That was greta of her to write you back and offer so much. She really does care.

So glad you got in touch with her. She had some really useful updates on her research. I often think of her as something of a Don Quixote (I know I can't spell!) because there really can't be that huge of an intellectual support community for something PDE research. She's fantastic!

I am definitely in on a gruop donation to keep her research going.

I love the idea of a group contribution from Pug Authority! Let us know details, I'm in.

I've emailed her back but it took about 2 weeks for her to respond last time so it may be a little while. I'll update as soon as I hear from her!

I'm going to post the info here that I have on my pug Timmy...in case anyone has a recomendation. I also sent this to Dr. Greer via email today. She mentioned 2 attachments in her letter to you Amanda...are they on here to read? Thanks SO much!!!
Maryann
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Brief:
3-yr-old male pug
2 seizures/muscle spasms 16 days apart
Stares into space
Stiff back legs after seizures…but can walk
Head pushing/resting
Lethargic

Detailed:
Timmy seizures – 3-yr-old male pug

8/6/2010 8:00am about 6 mins in length. He came to bed whined at me, he was sleeping. Was humping the air…asked him to stop, he flopped over and was flopping all around. When I thought it was done it started again & was worst. We held him & it stopped after about 6-7 mins.

8/22/10 5:00am about 6-7 minutes in length. He was again sleeping. He was on the bed & came over to me then started shaking violently. I held him & soothed him.

After both incidents he was “fine” after. He didn’t throw up like I hear dogs do after...he wasn’t panting…he went pee...later ate & drank normal. He does a lot of licking the air during it too. He licks the air other times too & has this cough thing he does…neither one seem like things that he can control. I thought this was new…but he used to “hump” the air before uncontrollably…maybe those were mini-seizures & now they are worst? He isn’t on meds. When you pet RT shoulder he is fine, when you pet LT shoulder he looks & seems sensitive. He presses his head on me, looks off blankly often...

I see that MRIs, brain biopsy, and spinal taps are the method of detection...I would do an MRI/CT but not the other 2...I'm not sure about how conclusive tests are though... I am reading that they have Chemo iv, atopica, and cytostar that are helping???

I also saw that antinflamatories can help with swelling...but still fatal. Which one?
And, that www.rescueremedy.com was something used....but whats a gimmick ad whats not....people are always trying to sell something.

The reason I found the info on PDE was because when I read things about epilepsy in dogs and seizures the info just didn't seem to fit....so I looked up muscle spasms in pugs. He doesn’t vomit, pant, pass out…or anything like that…

I'm not willing to give up on him...and I am of course in hopes (but not denial) about him possibly having this. THANKS!!

Hi Maryann, I'm glad you've found us here, so sorry about the circumstances. You are doing everything right for your boy - anticonvulsants and steroids can help. May I suggest you repost again in your own thread as sometimes people miss these posts when they're attached to these thread. I want to ensure all our members see your posts. You'll find a wealth of support and knowledge here.

This was recently posted. DNA testing to see if your pug is susceptable to PDE.

http://www.vgl.ucdavis.edu/services/PDE.php