German Shepherd Dog > DM Death Statistics in the GSD among the PDB members (159 replies)

by starrchar on 04 July 2012 - 18:02
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So, has the GSDM gene been identified? If so, what is it? Could it be a different form/mutated form of the SOD1 gene? Sorry if these are stupid questions, but again, just trying to understand this.
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by marjorie on 04 July 2012 - 18:11
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--- > So, has the GSDM gene been identified?

It way more complicated than just one gene :( I doubt there is a single factor involved, but rather, many and way more than one particular gene. On top of that, it would most likely involve rna, dark dna and impinting, as well of the matter of genes.
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by Gwenith on 04 July 2012 - 19:22
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Thanks Marjorie, Beetree and Hexe, I use iPhone. So I can't post photo. Maybe if Marjorie has time I can send her a few. Beginning(near beginning) until end. Blade is my soulmate and best friend. It is very hard to move forward with this decision. I know I must be strong for him. I will start new topic, when I set him free. But it won't be easy. Gwen
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by marjorie on 04 July 2012 - 20:55
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}}}}}}}}}}}}}}}}}Gwen{{{{{{{{{{{{{{{{{{{{{
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by darylehret on 05 July 2012 - 02:06
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From the samples taken (123), the SOD1 gene was the most common factor, with something like 4 or 5 other locations of interest (I forget exactly).  Might be the SOD1 gene was just 'incedentally' present as a SNP in the SO FEW german shepherds tested.  The gene is also associated with other diseases NOT degenerative myelopathy.

What *might* be the biggest problem, is that while Coates admitted that cases of DM was more prevalent in the german shepherd breed, his study mostly consisted of samples from corgis and boxers.  When only 74 samples and 49 controls across several breeds are examined, that's not a very fair representation for our breed.

Also to note, was that it was a genome-wide association study (GWAS), rather than a Linkage study, which samples across generations and could provide some clue as to the actual mode of inheritence.

The SOD1 gene was also a major player in another neurological disease similar to ALS (Lou Gehrig's), Spinal Muscle Atrophy, which is inherited as an autosomal dominant trait in Brittany spaniels, an autosomal recessive trait in Swedish Lapland dogs, and as of yet, an unknown method of inheritance in GSD's.

Evidence suggests that the primary cause for DM is immunologic or nutritional in origin, but neither cause is clearly established.

Just a suggestion, but if you send in your dog's dna and get it genotyped and sent back to you on disc, you can compare for yourself the SNP's in relation to the canine genome sequence (est. 2005) utilizing free software provided from various sources (such as Applied Biosystems).

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by gagsd4 on 05 July 2012 - 02:33
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I would think that if DM is the canine equivalent to ALS, then human researchers would be all over it. ------Mary
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by starrchar on 05 July 2012 - 02:59
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"I would think that if DM is the canine equivalent to ALS, then human researchers would be all over it.------Mary"
There are presently clinical trials taking place for a potential ALS drug. They have tested it on mice and now are using dogs with DM as models. My dog is one of the test subjects.
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by darylehret on 05 July 2012 - 03:04
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I didn't state that, but that's what Coate's study was aimed at finding, and not necessarily for our breed's benefit.  When the studies can be convincingly shown to have the potential to aid in human medical research, the doors for funding become wider.

Quoting Coates in this description of the study sponsored by the American Boxer Charitable Foundation,

Canine DM caused by SOD1 mutations resembles some forms of human ALS - Lou Gehrig's disease. Better characterization of the clinical disease spectrum in the DM affected dog, especially the nerve and muscle pathology will assist in establishing collaborations with ALS researchers and in development of therapeutic drug trials similar to those of human ALS. We hypothesize for this proposal that the nerve and muscle deterioration of canine DM will compare to that of human ALS. We are testing our hypothesis by performing clinical studies of the nerve and muscle and studying the pathology in DM affected dogs. The investigators were successful in obtaining matching funding from the ALS Association for completion of the proposed work.


Maybe the ALS Foundation might have an interest in matching the funding for a GSD specific study?  A report describing various neurological diseases in dogs actually compares Spinal Muscle Atrophy to ALS, though, with no mention of comparing ALS in it's Degenerative Myelopathy description.



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by marjorie on 05 July 2012 - 05:02
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---> Maybe the ALS Foundation might have an interest in matching the funding for a GSD specific study?

I dont know why they would consider it, since ALS does not involve sensory loss and GSDM does involve sensory loss. They would, in all likelihood, feel it is a diifferent disease, especially with the polar opposite results of diagnostic tests between ALS and GSDM. The MS society would probably be a better way to go for our breed. Our breed diagnostic tests match the results of diagnostic testing in MS.

Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group http://www.mzjf.info/hgate Heaven's Gate
 
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by marjorie on 05 July 2012 - 05:06
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--- >So, has the GSDM gene been identified?

Dr Clemmons found an allele for GSDM, which was a marker in GSDS that had a positive test. However, other breeds do not have that allele to have a change to it.


 
Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group http://www.mzjf.info/hgate Heaven's Gate
 
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by marjorie on 05 July 2012 - 05:10
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---> There are presently clinical trials taking place for a potential ALS drug. They have tested it on mice and now are using dogs with DM as models. My dog is one of the test subjects.

Starrchar, I remember you mentioning that a while ago! How is your dog doing in that trial? Have you seen an improvement? That would be wonderful, if so... How long has your dog been on it, now? I remember you were waiting to start it, last time I saw you post about it. You may have posted about it again, but towards the end with Missie T, I didnt have much reading time :( I hope you are seeing some good results! It would be so nice to read about even ONE dog beating DM! This disease needs to be stomped so deeply into the ground that it can never rise up again!

I am worried about Casey James. He is only 2 1/2 yrs old but being so neurotic about DM, I am fixated on his stance. He stands, too often for my liking, with his back legs slightly crossed, not under his body, but by his hocks. It could be because he is so focused on things- he focuses like no dog I ever had before, so perhaps its because he is tunnel visioned on whatever catches his attention, but it makes me frantic :(  I noticed on the GSDBBR that his great great grandfather sired a dog that died from DM. I am shaking in my boots.One more go round with DM would kill me, and if it didnt, I would *off* myself before living through it again. I cannot ever deal with that pain again- NEVER! If someone cut my heart right out of my body with a knife, while I was walking down the street, it would be less painful.

 
Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group http://www.mzjf.info/hgate Heaven's Gate
lf :(Another go round with DM would killme, and if it didnt, I would probably off myse 
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by beetree on 05 July 2012 - 13:00
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Wow, Darylehret, you said:
When the studies can be convincingly shown to have the potential to aid in human medical research, the doors for funding become wider.

You are so correct in your posts. I am duly impressed. That you bothered, as well.
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by darylehret on 05 July 2012 - 13:33
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And I've been sorely disappointed in you, as of late.  I might be a real right bastard, but I'm really a RIGHT bastard, more than you would guess.
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by beetree on 05 July 2012 - 13:49
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LOL!  Happens to me all the time, I just can't please everyone, so might as well please myself! Hey, give me credit for giving you credit, geeze! It took a lot  of effort on my part! 

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by darylehret on 05 July 2012 - 13:58
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I was like, "whoa, I gotta sit down," but I realized I already was.
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by beetree on 05 July 2012 - 14:09
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You are funny! LOLOLOL
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by starrchar on 05 July 2012 - 17:43
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Hi Marjorie,

Thank you for asking. Yes, I know the loss of MissieT was beyond devastating and I am so sorry. As you know all too well, only time will help. I sure hope your Casey James is ok. I can't imagine going through losing a dog to DM twice, let alone three times.  It is hearthwrenching, to put it mildly.

By the time the clinical trial started (2 months ago) Shelby was almost completely down. At first she seemed stronger and slightly improved, but it didn't seem to last. This is also what seemed to happen with the  stem cell therapy.  It is such a hard thing to assess the progress or deterioration of your own dog, but I can definitely say I've not seen anything significant or long lasting with this clinical trial drug. Today Shelby is having a good day and actually walked some, but who knows what tomorrow wil bring. Then, is it the drug, or is she just having a good day? What is interesting is that in this clinical trial the Boxers are showing a significant response. My vet says that Boxers typically deteriorate very quickly, usually gone within 6-8 months and this drug seems to have stabilized the ones that are in the trial. I am begining to wonder if possibly each breed has a slightly different form of DM. When I spoke to Dr. Vulliet at Regenavet labs in Davis, CA about stem cell treatment he said the German Shepherds seemed to have a good response rate, yet the Corgis did not. There is so much they don't yet know or understand... 



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by marjorie on 05 July 2012 - 21:28
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Starrchar,

I am so sorry there wasnt some good improvement with the drug or the stem cell therapy:( Dr Vuillet had contacted me about getting participants in my area, but Missie T was going through one of her bad periods. She was just about down and by the time I was able to get back to him, he had found someone in my area to find participants. ( It was before she went on Dr Clemmons experimental treatment.) I did ask him about Missie T receiving the stem cell treatment, but he said he wasnt having much success in dogs that were almost down or in late stage DM. Dr Clemmons had also tried stem cell treatments about a year or so before Dr Vuillet, and he  found the effects werent lasting. The dogs did show some improvement, but as soon as the stem cell therapy was halted, they went down again. I believe he did find, upon necropsy, that new pathways were beginning to form, but the connections werent there :(

Interesting that the Boxers are responding to the ALS drug. As you know, I do believe DM is quite different in Boxers than in GSDS. The results of Boxer diagnostic tests are more in line with ALS, and I am glad to hear they are having success with it in Boxers :) I cant help but wonder what would have happened with Dr C's trials with his experimental treatment  if the money didnt run out. I assume it would have to be a life long treatment, as once it was withdrawn, Missie T lost what she had gained.

You are so right- there is so much they dont understand about this disease. We need some serious research, appilcable to our breed or else this serial killer of a disease will keep on taking its victims. That is something I cannot live with.

My heart will be in my throat with CJ, as he exhibits no pain. He doesnt do it when he gaits- his gait is breathtaking. He only does it when he is standing stock still majorly focused on something, with intense concentration. However, it still makes me extremely uncomfortable. His prelims from the OFA for his hips were good, so its not his hips. I have put him on Dr C's healthy dog program, which I believe mitigated Missie T's DM, as she was on it from the time she was 6 months old. Most young dogs go down fast, in DM. The disease progresses much more rapidly in younger dogs, probably because their immune system is stronger, and GSDM, being an autoimmune disease, is affected by an immune system in full gear. (One should never give a dog with GSDM anything to stimulate the immune system. In GSDM, the immune system needs to be not stimulated to stop the disease from progressing faster.) However, young dogs have stronger immune systems than older ones, which is why I think the disease progresses faster in the younger ones. My neice has Lupus, also an autoimmune condition, and they give her chemo to crash her immune system whenever she gets a bad period.

Sending prayers for Shelby to have some more good days!!! Give her a big hug for me, please. Try to live in the today- easy to say, I know, butharder to put it into practice. However, if you focus too much on the tomorrows, not only will the tomorrows be bleak, but the todays, as well... Hang in there!

Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group http://www.mzjf.info/hgate Heaven's Gate
 
Edited by marjorie on Fri Jul 06, 2012 01:05 am ::
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by marjorie on 08 July 2012 - 18:17
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For those you you who questioned Dr Clemmons GSDM research, how money is collected and where it goes,  please see the thread started by AbbyNormal in relation to DM research

http://www.pedigreedatabase.com/german_shepherd_dog/forum.read?mnr=636665

I didnt see any reponses from anyone here acknowledging this new thread, while there certainly was some serious questioning done in THIS thread.

Also, please note, for those of you truly concerned about DM research, there is now an easier way to donate to Dr Clemmons GSDM research! Go to abbynormal's thread linked to, above.


 
 
Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group http://www.mzjf.info/hgate Heaven's Gate
 
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by hexe on 08 July 2012 - 18:27
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Marjorie, I didn't see any reason to comment in this thread on the link Abby provided--I just used the link to make a donation.  I agree that this IS easier than the previous arrangement, which required a check be sent, because it's always easier to be able to do something instantly with a credit card and the Internet, than to have to dig out the checkbook, write out the check, address the envelope, put a stamp on it and get it into the mailbox...so it is a big step forward. 
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