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by marjorie on 07 August 2008 - 04:08
wel, she did study GSDS, at one time, when the GSDCA funded her, when she preformed so dismally....
by Aqua on 07 August 2008 - 13:08
@Blitzen:
"I posted this link here weeks ago. As far as I know there was not one single response to it."
There were actually 21 responses. My own suggested caution because this test doesn't diagnose DM. It identifies genes which may or may not express themselves in the disease.
The earlier thread is located here, in case anyone wants to review it:
http://www.pedigreedatabase.com/gsd/bulletins_read/208178.html
by Blitzen on 07 August 2008 - 16:08
Aqua, that was my second post regarding this test. There were no responses at all to the first.
by cledford on 07 August 2008 - 16:08
I have a lot of respect of Dr. Clemmons and believe I might have DM dog – so adhere to his protocol re. feeding, supplements, exercise, etc. I’ve even tried the DM medicine for several months, saw improvement, but have since ceased the therapy with no decline either suggesting either he has DM (and responded to drugs) or has something else and partially recovered during the DM therapy as would naturally occur whether taking DM meds or not.
The point is that DM diagnosis is one of attrition and my dogs issues could just as easily be related to a number of other neurological problems, those possibly relating to orthopedic issues - such as a spine/disk injury. Since the process to eliminate the other potential causes for his symptoms requires either MRI or CT (costing several thousands of dollars) it just isn't in the cards (or more specifically the bank account) to get to the bottom of things at this point. Therefore, I would be VERY interested in a genetic test, even though it still might not definitively show what his issue is, i.e. he is A/A but has not developed DM, however due to spine injury is showing neurological symptoms none the less. Zeroing in with a genetic test that one would assume would only cost a few hundred (max) vs. a few thousand would still be very welcome. So here is my issue - I read the excerpt above and it seems VERY straight forward. I've read about the FLASH test and it appears much more complicated to make a determination from. I've read the criticisms of the Vets involved in the test that prompted this thread, but I’ve also heard equally (actually worse) disparaging things said about both Dr. Clemmons and the FLASH test.
So who has the more accurate test? With regard to GSD specific myelopathy, I don’t get it. GSD is a breed, but genetically ALL dogs are thousands of times more alike than different, so I would assume that DM for one breed is the same for another. Is this incorrect? I guess I have issues with the suggestion that as GSD owners we should support vet more who is working with our specific breed simply because they work with our breed. If there is compelling reason (i.e. the DM triggers are different from breed to breed) reason to support Clemmons work over the other please share it – otherwise why not support BOTH? Frankly, I don’t care who (or what breed they primarily work with) comes up with an accurate test, just that someone does.
-Calvin
by Blitzen on 07 August 2008 - 17:08
Calvin, so far Blitz has not shown any signs that would make me think he may be in the early stages of DM. However, he is only 6 1/2 but given he's a GSD, I am naturally concerned that it may develop in the future. I want to know if he is subject to that happening and have already submitted his DNA for this test. If the result should indicate he is likely to develop it, then I will follow Clemmon's protocol and take advantage of the Flash test. Since I'm not seeing anything that makes me suspect DM, I see no value in having the other tests done just yet.
I look at this test as a preliminary test and Clemmon's work as the follow up for a dog that is a candidate to develop DM. Even though some dogs test "positive" and never develop symptoms, I still think it's important to know the status of my own dog and do what I can to stave off the disease - that would be taking advantage of Clemmon's research. I also think it's important to participate in this study since it may give us some answers as to why some dogs who test positive do not develop DM. Is it diet, the type of exercise they do or do not get, is there another gene involved that surpresses the expression, is it something in the way the dog is constructed? What about a past injury? So many unanswered questions. I'm happy to see that this test is available. It's not perfect, Dr. Coates admits that herself. BTW she is also recruiting DNA from dogs with some other diseases, dwarfism is one I think. She is leaving the US and will soon be relocating to Australia. I don't know anything about her research as funded by the GSDCA but I have met Marjorie and her comments have given me cause for concern since her only agenda is finding a cure for this horrible disease.
If I buy another GSD I will want to know if the parents have been tested with either protocal and the results. OFA now has an area for GSD's that have been tested using the Flash test. So far there are only about 10 dogs or less listed and all have tested negative. Maybe one of these tests (or both) will some day be as important as hip and elbow certs.
by marjorie on 08 August 2008 - 22:08
--- > GSD is a breed, but genetically ALL dogs are thousands of times more alike than different, so I would assume that DM for one breed is the same for another. Is this incorrect?
Yes, this is incorrect, and here is why....
All breeds can get a degenerative condition of the spine, which is both chronic and progressive, called Degenerative Myelopathy. However, the Degenerative Myelopathy of other breeds is not the same disease German Shepherd Degenerative Myelopathy. German Shepherd Dog Myelopathy (GSDM) is unique.
DR Coates has worked under the theory that DM is ALS. Amyotrophic Lateral Sclerosis and related diseases are motor unit diseases where the nerve cells in the body responsible for controlling movement die off leaving the patient weak and with varying degrees of Lower Motor Neuron dysfunction (loss of reflexes and flaccidity) or Upper Motor Neuron dysfunction (hyperactive reflexes and spasticity). Those causing LMN disease affect the EMG early in the course of the disease. Those causing UMN disease result is selective shrinkage of the motor cortex visible on MRI. Neither of these conditions exist in GSDM.
Immune diseases like MS attack varying parts of the nervous system and one of them, Primary Progressive MS, specifically targets the myelin and axons of the spinal cord leading to UMN signs but without affecting the cell bodies of the neurons (which is what is seen in GSDM on histopathology). The CSF protein is usually normal in ALS, but abnormal in MS. Oligoclonal bands of IgG are common in MS and uncommon in ALS. The recessive forms of ALS are extremely slow in development and do not result in shortened life-span. Even the one motor unit disease known in dogs, Spinal Muscle Atrophy in Brittany Spaniels occurs in young dogs with progressive EMG changes leading to death. That might be more consistent with the “early onset DM reported in the GSD which is not the same disease as GSDM on histopathology.
ALS diseases cause motor problems but not sensory ones. That is they do not cause CP deficits or hypermetria (ataxia in which movements overreach the intended goal.). People do not knuckle and scrap their toes when they walk, they only show weakness. Most of them are painful because of muscle spasms. (Does that sound like GSDM?....NO!)
So, even if there is a genetic change in SO
by marjorie on 08 August 2008 - 23:08
UGH- I can see it will take several posts to get the facts in place :( so, to continue...
So, even if there is a genetic change in SOD1, Dr Clemmons believes that a change must also be explainable based upon the clinical signs. If not, it may just be a casual relationship not a causal one. GSDM as a pure motor unit disease just does not fit all of the available data. (Not just DR Clemmons…everyone's!)
To simplify- lay person's explanation:
DM Corgis, Boxers, : motor unit disease
DM GSD: Auto-immune disease
DM Corgis, Boxers : Protein is normal in the AO CSF
DM GSD: Protein is normal in the AO CSF but Protein is elevated in the Lumbar CSF
DM Corgis, Boxers: Oligoclonal bands of IgG are uncommon
by marjorie on 08 August 2008 - 23:08
DM GSDS: Oligoclonal bands of IgG are common in MS
DM Corgis, Boxers: affects cell bodies of neurons
DM GSDS: Does not affect cell bodies of neurons
DM Corgis. Boxers: muscle spams
DM GSDS: no muscle spasms
DM Corgis, Boxers:EMG is affected early in the disease
DM GSDS: EMG is normal
by marjorie on 08 August 2008 - 23:08
From DR Clemmons:
“They are (similar the DM Flash test and the gene test). The main difference is that without the resources of MIT behind me, I had to look to see if there was a genetic relationship to GSDM and using what we had that was reasonable, we use RAPD (random access repeat primers) to look at the genome. Using these, we found a pattern that was consistent in GSDM (and other forms of DM). While we initially looked at a specific set of primers that we looking at the IRB1 region and found a change there that was consistent in many GSDM patients, it was not as consistent in all of them as the change in the RAPD analysis. Although we did not continue to call the test in other breeds the DM Flash test, we continued to call the test in the GSDs that in honor of Jack Flash. We also have seen several other changes that exist in GSD patients that are consistent, but we track the DM Flash test to confirm the diagnosis. Of course, since demonstrated the potential to find the gene associated with GSDM (and other DM cases) and that developed the interest in other researchers who have now found the change in the SOD1 region of the canine genome. They were able to use the 18000 SNiP array (we could not afford them since they were $2400 each), but MIT had developed these when they did the canine genome project. The major difference between SNiPs and RAPD is that SNiPs let you put a gene name to the product and the RAPD does not (as easily). RAPD also may find something that SNiPs do not and vice serse, but it does appear they have found the same thing here (or there are more than one change which is still possible). We took a different tact in using the RAPD, which was to determine the incidence of the gene change so we determine it effectiveness as a diagnostic. As such we found that 25% of the dogs care the trait we track, but only 10% of these ever develop GSDM. So, it makes a poor screening test. Yes, 91% of the reason for developing GSDM is due to the genetics and patients who are positive in the DM Flash test have a 12 fold increase risk of developing GSDM, it cannot be the soul factor as to why they eventually develop GSDM. On the other hand, if an older GSD has clinical signs, it is a great diagnostic test with a 96% sensitivity and 99% specificity. I correctly identifies those dogs who have GSDM from those (proportionately more) who do not have GSDM once clinical signs develop. Probably the gene test does that, but we do not know for sure, since they do not have that information about their test yet or at least have not presented it. The gene test might do one thing that we currently do not (although future versions might) in that it may be able to tell who is a carrier of the risk factor. We have only tracked those who are at risk and are homozygous for the trait. However, since the gene is not the soul factor for developing DM, I am not sure that genetic testing and elimination of carriers and at risk patients is appropriate. Based upon our work, that could mean removing 75% of GSDs. That is foolish.
Dr. Coates has stated that since the gene involved in their work is the SOD1 gene, that DM is a motor unit disease and an animal m
by marjorie on 08 August 2008 - 23:08
Dr. Coates has stated that since the gene involved in their work is the SOD1 gene, that DM is a motor unit disease and an animal model of ALS. In that, I still believe she is wrong. We have never been able to demonstrate selective motor unit involvement even in late cases. ALS does not have sensory abnormalities which would include proprioceptive deficits which are a predominate feature in DM. We do not think you can build a puzzle by starting with the last piece; the puzzle is built from all the pieces. Only when all the pieces fit together, can the whole picture be seen. Too much data says that GSDM is an immune mediate chronic neurodegenerative disease associated with demyelination and axonal loss. This is most similar to PPMS rather than ALS. The fact that the SOD1 is involved complicates things because it is means that DM may be a “bastard child” where the change in SOD1 triggers the immune disease and attack of the nervous system and so it looks like a cross between ALS and PPMS. As such it is not a pure model of either. However, the truth is the important thing. With that, we can devise appropriate strategies to combat it.
Dr. Coates has made a few mistakes in her work on GSDM which is a bit surprising, but they are real. One study was nullified since the case selection led to only 3 dogs in the study of 12 that actually had GSDM. On the other hand, this confirmed our work and that clinically only 25% of the patients who present with signs of posterior paresis actually have DM. She suggested that all dogs have oligoclonal bands and, therefore, they were not important in DM. This is not true and we found that 60% of GSDM patients do have more than one unique clonal band in lumbar CSF which is the definition of oligoclonal band positivity. Finally, she keeps looking for CSF changes in DM in the AO CSF which we have repeatedly shown to be normal. CSF changes in DM occur in the lumbar CSF and if there are changes in the AO sample, there is something other than DM. Her work provides pieces of the puzzle, but only if the rest of the puzzle is considered. We have tried to provide those pieces. For years, I was the lone voice and criticized by many. Now, I have a chance to do the same, which is refreshing.
What I do not know is whether Dr. Coates (or anyone from her team) will assist and really answer questions about the gene test or the disease. I respond to 2-3 people a day on average about GSDM and have tried to provide real information to be of help. I do that because I am compelled to help people; but I will not be able to help people who decide to perform the gene test instead of the DM Flash test, since I cannot comment upon someone else’s data. I guess one must decide who to support, one who has consistent supported them or not. If the gene test eventually becomes the DM test of the future, that is fine, but it is important to continue research into the other associated regions we have looked at, since the answers are going to come from them. The fact that my team (me and one technician) have been able to compete with MIT (and the horde) should be pretty impressive. Sadly, they have probably effectively dried up our sources o
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