[ SHOWGSD-L ] Fwd: Discussion on DM
- From: RopajaGSD@xxxxxxx
- To: Showgsd-l@xxxxxxxxxxxxx
- Date: Mon, 23 Jan 2012 22:32:22 -0500 (EST)
From another list, permission to cross post given and approval to post
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Sent: Monday, January 23, 2012 4:30 PM
Subject: Discussion on DM
Fact:
"ALS does not affect a person's ability to see, smell, taste, hear, or
recognize
touch."
You can pinch the foot of a dog with DM, and they wont feel it, so how can
this
be reconciled with ALS not affecting the ability to recognize touch?
Fact:
" ALS Patients usually maintain control of eye muscles and bladder and
bowel
functions, although in the late stages of the disease most patients will
need
help getting to and from the bathroom.""
In DM, when the hind end goes, so goes bladder and bowel and bowel
control...ask
anyone who has had a DM dog if that dog has been able to maintain bladder
and
bowel control. The answer is "NO!" Again, how can this be reconciled with
ALS,
when DM dogs lose control of bladder and bowel?
Fact:
" Not all familial ALS cases are due to the SOD1 mutation, therefore other
unidentified genetic causes clearly exist." In fact, only 10-20% of people
with familial ALS have a change to the SOD1 gene.. What about the other
80-90%? Only 2% of people with non familial ALS have a change to their SOD1.
FACT:
"The parts of the body affected by early symptoms of ALS depend on which
muscles
in the body are damaged first. In some cases, symptoms initially affect
one of
the legs, and patients experience awkwardness when walking or running or
they
notice that they are tripping or stumbling more often. Some patients first
see
the effects of the disease on a hand or arm as they experience difficulty
with
simple tasks requiring manual dexterity such as buttoning a shirt, w
riting, or
turning a key in a lock. Other patients notice speech problems-slurred and
nasal
speech; or difficulty chewing or swallowing."
Interesting- DM always progresses from the rear, moving towards the front
of the
body. I have never heard of a dog with DM having problems with its front
end,
front legs, or chewing and swallowing, before it is already down in the
rear.
These are just some of the reasons that make ALS a poor candidate to be
called DM in the GSD. I cannot speak for other breeds as I am not familiar
with DM in other breeds.
It is hard to believe, to those very familiar with DM, that DM is caused
by a change to ONE gene (especially when genetically only 10-20% of people
with familial ALS have a change to the SOD1 and only 2% of people with ALS
that is non familiar have a chnge to the SOD1.). By taking that position,
one is denying the undeniable influence of dark dna or RNA. Dark DNA, for
those who do not know, is basically the concept that other genes influence the
expression of the main genes that are thought to control genetic disease
transmission. This is also the concept of gene â??imprintingâ?? where some
genes
turn on or off and those influence whether other genes function and
therefore create consequences. The presence of a single gene change which does
not explain who actually gets the disease is only part of the answer. If you
donâ??t find which other genes determine whether the â??primaryâ?? gene acts,
you are missing the answer.
Known mutations in SOD1 account for about 2 percent of all cases of ALS.
... This means only about 2% of all patients with ALS have the SOD1 genetic
change. How can a change to the SOD1, in the light of this fact (statistics
published by the ALS Association) be the sole cause of DM. It cannot be,
if 98% of those diagnosed with ALS have no changes to the SOD1. There is no
way to determine, at this time, if changes to the SOD1 are a CASUAL or
CAUSUAL relationship, and there is a world of difference between the two! Food
for thought, at any rate...DM just doesn't present as ALS, not even when you
compare test results between the 2 diseases. They are worlds apart
There has not been one documented case of DM in the GSD beginning anywhere
other than the rear of the dog. Bloodwork, CSF, EMG, MRI and complete
Neuro exams give a complete picture of what areas are affected and where the
problems lie. That is why proper testing is so important, and eyeball
diagnosis are worthless
Routine diagnostics are essential to finding what is causing each disease.
There are more things that look like GSDM until you look for the cause. In
the end, a thorough necropsy sorts out many of the rest if they cannot be
found before death from the disease. Unfortunately not enough people pursue
a clinical answer and even fewer perform necropsies at the end to get a
pathological diagnosis. Without doing one or both, then most of it is just
guessing based upon typical presentations and causes for those presentations.
That might have been good enough 40 years ago, but not so much, now.
However, profile and signalment, history with clinical signs are how a
differential diagnosis can be reached.
As far as diseases being related, or stemming from one problem rather than
another, well, I guess all diseases could be swept into a broad category
of an immune system failure. However, the etiology of different diseases,
the course, the presention and the diagnostic tests for that condition is
what makes each disease unique. For example, a condition affecting the upper
portion of the spine, possibly mimicking DM, but starting in the cervical
area is Wobbler's disease. There are different diseases affecting different
portions of the body, and they cant all be lumped into one neat category and
it doesn't make them related. That is why there are specific tests for
specific diseases. That being said, it is quite possible for any dog, as any
human, to have more than one condition at a time. However, the
ailment/ailments, be it multiple or singular have their own unique etiology. It
is
believed that dogs with DM have a greater incidence of perianal fistulas,and
vice versa. However, DM is not PAF nor is PAF DM. If the condition affecting
the dog had a different etiology than DM, simply put, it would not be DM, but
in fact, an additional/another disease which fit the etiology of that
particular disease, running concurrently with the DM. DM does not present in
the larynx or esophogus-in fact, that is the LAST place it goes, AFTER the
dog is already down in the front and the rear. That is not the course and
presentation of DM, but rather another disease. Thus the diagnostic tools to
help rule in and rule out other diseases. A rose by any other name is still
a rose, and in order for a disease to be found, etiology and diagnostics
are used for diagnosis. You cant call a chest cold "pneumonia". There has to
be a certain set of criteria utilized to make a diagnosis. I suppose one
could call it whatever one wants to call it, but that doesn't mean the label
is correct. To make a correct diagnosis, again, one must stick to the facts
and follow testing procedures for that particular condition.
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, aka
LMN, (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 â??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 SOD1 that change must also be
explainable based upon the clinical signs. (again, only 2 % of people with
ALS have a change to their SOD1 gene!) 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.
In case I lost anyone in the above explanation, here it is in lay person's
terms:
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
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 spasms
DM GSDS: no muscle spasms
DM Corgis, Boxers:EMG is affected early in the disease
DM GSDS: EMG is normal
So how can one scientifically explain away these major differences? I can
call black "white" but that doesn't make it so. It must be born out by test
results. 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 in
2% of the cases complicates things because it is means that DM may be a â??
bastard childâ?? 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.
Dr Coates believes 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.
Again, the DM of the Corgi and Boxer is not the same as the DM of the GSD.
Perhaps in other breeds DM is/is more similar to ALS, but in the DM of the
GSD, that is just not the case, born out by the facts and diagnostic
tests. Again, I know nothing about DM of other breeds, but I am well educated
about the DM of the GSD...I do believe the problem ensues when DM is used
across the board as a *catch-all* phrase for all breeds. All breeds get a
degeneration of the spine which is both chronic and progressive, but the DM of
the GSD is a unique disease. Dr Clemmons program does not work on Corgis
and Boxers, it never has, giving rise to even more evidence of a difference
between the diseases, both of which are called DM. Therefore, the disease
our breed gets should always be referred to as GSDM-German Sheperd Dog
Myelopathy, which is just not the same disease, clinically or diagnostically,
as
the DM of the Corgi/Boxer which was the foundation breeds of the ALS/DM
study.
I dont know how to explain it any more clearly. If it is not
understandable, then I have failed miserably to educate That failure,
however, would
not be for a lack of trying...
There has not been even ONE documented case of GSDM starting anywhere in
the body other than the rear or even ONE documented case of GSDM producing
different diagnostic test results...I would venture to say, however, that if
it did, it would be a different disease and not called GSDM. It would not
be DM of the GSD because the test results are the test results, and the
science behind it and the differences cannot be ignored. The marked
differences
between the diagnostic results previously mentioned, ie the EMG results,
the type of disease, Oligoclonal bands present in one not the other, the
muscle spasms vs no muscle spasms, the incontinence in one and complete lack
of incontinence in the other, cell body neurons in one being affected, cell
bodies in the other not being affected, and so on and so on, point to two
different disease processes. 2+2 always has to equal 4. It cant equal 5.
(Well, unless I am doing the m-m-m-m-m-m-m-ath... LOL! not my strong suit
Ok- now my turn to question... How many of you believe the there is only a
change to ONE gene that is responsible for ALS, in humans and in other
breeds? How many of you believe that RNA or dark dna plays no role in
determining who gets DM, or ALS for that matter?
I cannot help but question HOW one test that hasnt been around long enough
to follow several generations, can claim to produce DM free lines.. I am
worried that unethical breeders will seize upon this, when there is no
science to prove this will be the case. There cannot be science in this, as
generations havent been followed to prove this is a correct and valid claim.
It
worries me tremendously that dogs are being thrown out of a gene pool
because they carry a change to their SOD1 that only 2% of people with ALS
possess.
No one could want DM eliminated more than I do. I have been through the
horror of this disease 2 times, now. I have lived, slept, eaten, breathed and
enveloped my life in battling this disease. It was a promise I made to
Jack Flash, as I held in my arms for the last time. It is a promise I think
of, everytime I look at my sweet Missie T, who is now in the advanced stages
of DM. It worries me that dogs are being prematurely cut out of a gene
pool, making a small gene pool already smaller. Working lines breed to working
lines, show lines to show lines, obedience to obedience, am bred to am
bred, german to german.. The germans look down on the Am breds and the am
breds
look down on the german bred dogs. We have already subdivided the breed
into so many small sections that I am afraid we are bringing bigger problems
upon our breed by eliminating dogs based upon the change to the SOD1, which
again is 2%!! Like it or not, there are politics in research, just like
there are politics in anything else.
Does anyone really believe that politics has had no input in the pushing
of the SOD1 DNA test? I know better, sadly, as I have been up close and
personal with the AKC and caught them with their panties around there ankles
as
did several prominent members of the breed, who witnessed this incident.
By prematurely knocking dogs out of a gene pool, we bring other diseases
closer to the forefront and breeding on those traits, while not even being
sure the dogs were removed for good reason. One must be careful what one
wishes for, if that wish is not closely monitored for accuracy in reality.
JMHO,
of course...Please just think about what I have said and ask yourself how
one can predict the future, when one hasnt even walked halfway down the
road...Where is the proof that future generations of clear dogs will never
develop DM...How can one make that claim, without having studied generations
of clear dogs???? and how can one categorically state that there is only ONE
gene responsible for DM, when not enough is known about the triggers for
the disease? Maybe its me, but I see the Emperor's New Clothes.. He is butt
naked.. Again, JMO, for what its worth.
The test for DM is no longer available due to a lack of research funding
Someone has to be paid to run the test. Dr C will run some for me if I ask,
but there just isnt enough dollars to run it in the open way he was
running it before. We ran out of funding. I have an offer to publish the book
I
wrote "Things I learned from my Dog" but have no time to work on it with
Missie T being so ill. If I had the time, I would do what needed to be done
with it, and donate all the profits to DM research, as I did when I sold it on
my own to benefit DM research.
Someone asked me if If the Coates work can be fully generalized that means
the dog would never develop DM. However, my answer to that is IF and ONLY
IF the relationship between the changes to the SOD1 are causal and not
casual... and IF and ONLY IF you buy into DM (*catch all* DM of other breeds)
being the same disease as GSDM. I personally do not believe they are the same
disease, for if they were, there wouldn't be the tremendous discrepancies
between the results of the diagnostic test results. They are not even close-
they are at opposite ends of the spectrum. How does one reconcile the
science of the results being so drastically different?
The GSDCA gave Dr Coates a huge amount of money to research DM of the GSD.
Upon necropsy, only 3 out of 12 dogs were found to have been correctly dx
with DM. That is a dismal record- she would have received an "F" if her
research was college graded.
I did read her research paper on the SOD1 and only 4 GSDS were used in her
original research- the rest were Corgis, Boxers and other breeds which
never responded to Dr C's protocol (again pointing to a different disease
process). The paper mentioned that one of the methods of subject choice was
clinical signs of DM. With her history of only 3 out of 12 being correctly
diagnosed in the past, I did not get a warm fuzzy feeling as she clearly
showed in her GSDCA research that clinical signs are not a reliable way of
diagnosing DM. Despite that record, once again clinical signs was one of the
criteria she used for her SOD1 participants
People flocked to purchase Methionine, when she did her GSD research for
the GSDCA. However, too much methionine is a bad thing - biochemical
measures of damage and good operation that are improved by lowering methionine
intake are instead made worse when methionine is supplemented in the diet.
Increased Methionine led to oxidative damage to mitochondrial DNA in test
subjects conducted elsewhere. More oxidative damage is a bad thing Needless to
say, her research clearly showed methionine had no effect upon GSDM. It
would have been highly unlikely for Methionine to help DM because in her
original abstract, she referred to DM as a muscular disease, which it was NOT!
I
do believe she changed that abstract after my communications with her.
I have found in my research that the AKCCHF will repeatedly fund the same
people for research, no matter how successful or unsuccessful they have
been in their research. This is easily validated by going through The AKCCHF
web site, looking under grants that have been distributed to researchers
(unless they changed it from the time I did my research). The results of the
researchers success doesn't seem to matter to them. I also have a problem
with an organization that condones and knows about the lifting of other
researchers work, rewarding such behavior by allotting grant monies to
researchers who engage in this practice, and granting research monies to
proteges who
work at Universities they, themselves, work for. IMHO, that is a conflict
of interest.
At any rate, I wished to give an explanation for my marked skepticism, just
to allay one's impression that my stance is an arbitrary one.
Missie T on an experimental program, from Dr Clemmons, on which she was
doing amazingly well, but it is not a cure. The program can do no harm, but we
werent sure if it would help. She was basically down when we began the
treatment. It DID help in an almost unbelievable way for 7 months! There have
been zero negative side effects in the 7 months she has been on it.:) Up
until last week, each time her treatment was administered, she would get up
on her own and walk from one room to another on her own (whereas she could
not do this before) and I only had to lightly hold her up by her rear end
harness if she walked further distances. Her rear was not the dead weight it
was, before beginning treatment. She was good like that until the night
before she was due for the next treatment, then she would crash. With the
administration of the treatment, she would be good until the night before the
next treatment. We are possibly going to be upping her dosage in the hopes
it will help.
At any rate, people really need to educate themselves, and ask how, without
a follow up for several generations, that one can say, with any validity,
that a clear DNA SOD1 tested clear dog bred to DNA SOD1 tested clear bitch
will produce GERMAN SHEPHERD DM free dogs. IMHO, that is a silly notion,
possibly misleading and downright irresponsible without generational follow
up studies. If one showed me 10-15 years of progeny of SOD1 tested GERMAN
SHEPHERD dogs never developing DM, at that point, I might be convinced. We
are not at that point, however. In fact, we are far from it :(
Marjorie
_http://www.gsdbbr.org_ (http://www.gsdbbr.org/) The German Shepherd Dog
Breed Betterment Registry
BE PROACTIVE!
_http://mzjf.com_ (http://mzjf.com/) --> The Degenerative Myelopathy
Support Group The same DM as the DM of the Corgi, Boxer, and other breeds used
in the research of Dr Coates when she discovered her mutation to the SOD1
which she feels makes DM ALS, and not Primary Progressive Multiple Sclerosis.
You have my permission to post this to the showlist, if you wish for those
who have a desire to learn and understand that the facts are important, and
that the scientific diagnostic test differences between the two diseases
are completely juxtaposed- they could not be at more opposite ends of the
spectrum! We need an education in FACTS, not an education on politics of
researchers.
Pauline Moon - _www.ropajagsd.com_ (http://www.ropajagsd.com/)
Ropaja German Shepherds:Member-GSDCAmercia & GSDCAtlanta - Best In Show
AKC JAM/AOE/ BISS CH Ropaja's Chateau Beaujolais OFA HIC; BISS AKC CH
Ropaja's Chateau Beaulieu OFA HIC; Multi BOB & GRP W AKC CH. Ropaja's Je Suis
Fleur De Lis; Multi-BOB & GRP W AKC CH Ropaja's Je Suis Gabrielle.
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