Photo by Rich Paice
Is Degenerative Myelopathy a problem in Deerhounds?
by John Dillberger, DVM, PhD
Reprinted from the May/June 2025 issue of The Claymore.
Degenerative myelopathy (DM) is a spinal cord disease that begins late in a dog’s life and causes gradual paralysis, starting in the hind legs and moving toward the front. It is a progressive disease with no cure or effective treatment. Consequently, DM usually ends in euthanasia, out of concern for the dog’s quality of life.
Does DM occur in Deerhounds?
The answer is YES. The 2011 Deerhound Health Survey results include four bitches and a male for which the owner listed DM as the reason for euthanasia. The male was 10 years old; the bitches, 12 to 14 years old. But these 5 cases are not the whole story.
Another five bitches were euthanized between 10 and 13 years of age due to spinal arthritis (spondylitis) and/or bone spur formation between vertebrae (spondylosis). These conditions can make a dog stiff and uncomfortable. But for two of these bitches, the owners’ comments were “lack of mobility at the end” and “could no longer get up on own,” which suggest possible DM. Just because a dog has spinal arthritis and bone spurs does not mean it cannot also develop DM.
But the most revealing comments were from 17 owners who euthanized their dogs due to Old Age. All but one of these owners provided comments indicating that hindquarter issues were the reason for euthanizing these 8 bitches and 8 dogs:
“Loss of mobility”
“Rear end gave out.”
“Could no longer get up.”
“Unable to get up or down.”
“Old age, hind limb weakness”
“Rear end weakened” (2 dogs)
“Incontinent, difficulty getting up.”
“She could no longer stand or walk.”
“No longer able to get up and down.”
“Typical old age – weak rear, incontinence”
“Unable to walk well any longer, quality of life.”
“General old age failure such as incontinence, could not get up.”
“She was falling because she was very unstable walking.”
“Hind end failure – euthanized when he could no longer stand or walk.”
“Lost use of one rear leg and had only partial use of other, possibly spinal degeneration or possibly from advanced arthritis”
Clearly, Deerhound owners equate progressive hind quarter issues with old age. In other words, they EXPECT their Deerhound’s rear end to fail if it lives long enough. Did some of these 16 dogs have undiagnosed DM? I think it is likely, for a couple of reasons.
First, DM is a tough diagnosis to make in life because there is no test for the disease. Instead, DM is diagnosed by exclusion, which means ruling out other causes of progressive rear end weakness in an old dog. As the VCA Animal Hospitals website puts it, “the diagnosis of DM is a challenging, often time-consuming, endeavor, requiring many tests before a definitive diagnosis is made.” What the VCA website does not add is that the process also is expensive. For many reasons, a Deerhound owner whose old dog is slowly failing may opt NOT to do extensive and costly evaluations to determine the cause.
Second, although DM is easy to diagnose after death by examining the spinal cord microscopically, this requires that spinal cord samples be collected at necropsy. This is not standard practice at veterinary diagnostic laboratories because it takes a lot of work. Consequently, the spinal cord will be examined only if the referring veterinarian or owner specifically requests it.
DM Signs and Symptoms
DM appears late in a dog’s life, usually after 8 years of age. The first signs can be subtle changes in the hind quarters. You might notice weakness in the rear legs or difficulty getting up, swaying in the hind end while standing, or slight changes in gait, such as occasionally taking a wrong step or swaying in the hindquarters while walking. When you look at the dog’s feet, you might find scuffing of rear paw pads or wearing on the innermost nail of the rear paw. When you pet the dog, you might notice it has less muscle mass in the hind legs. If the dog is prone to wagging, you might notice less active tail movement or a change in tail carriage.
DM is a progressive disease, meaning once symptoms begin, they will worsen with time. In the early stages, bladder and bowel function are normal. But as the disease progresses, urinary and fecal incontinence will develop in conjunction with hind-limb paralysis.
Diagnosing DM
As I mentioned earlier, DM is diagnosed in life by exclusion, which means ruling out other possible causes of progressive hind quarter weakness. This might involve blood tests, X-rays (with or without injected contrast material), spinal fluid analysis, or advanced (and expensive) imaging using computed tomography or magnetic resonance imaging. The latter also require anesthesia, which can be risky in an old dog.
Treating DM
There is no treatment to cure DM or stop its progression. Once the symptoms begin, the damage to motor neurons already is done. That damage is irreversible because the underlying disease process that caused the damage cannot be stopped.
That said, various supportive care has seemed to help in some cases, although the reports are anecdotal. Giving antioxidant supplements, exercise, acupuncture, massage therapy, physical therapy, and electrical stimulation of muscles all have been reported to help. Keeping a dog with DM at a healthy weight and providing soft bedding to prevent bed sores can help.
Ultimately, the dog’s quality of life will decline to the point where euthanasia is the right choice. You also must consider your own quality of life. If your life now revolves around carrying your dog from one room to another, turning them to avoid bedsores, cleaning up after a paralyzed dog, staying home so they have around-the-clock care, entertaining them, protecting them from things they cannot move away from, and straining your own body to carry and move them, that might not be healthy or safe for you.
What causes DM?
At present, we do not know what causes DM. But we are beginning to understand, partly because DM in dogs closely resembles amyotrophic lateral sclerosis (ALS, aka Lou Gehrig’s Disease) in humans. Both DM and ALS result from degeneration of spinal cord nerve cells called motor neurons, which control voluntary movement. Both diseases appear in middle-aged or older individuals.
Most ALS patients (90%) do not have affected first-degree relatives and are described as sporadic cases. The other 10% run in families and are considered at least partly hereditary. Since 1993, variants in more than 40 genes have been associated with familial ALS.
The most frequent variants in familial ALS are in the gene that codes for a protein called superoxide dismutase, type 1 (SOD1). Over 185 (!) distinct SOD1 variants have been identified so far (Berdyński et al., 2022). But it is still unclear if the variant SOD1 proteins cause ALS, contribute to ALS, or just accompany ALS.
The situation with respect to SOD1 variants and DM is similar in dogs. On the one hand, a variant SOD1 gene is present in most, if not all, dogs diagnosed with DM. The trouble is, the SOD1 variant also is present in a lot of dogs that do NOT have DM. Clearly the SOD1 variant alone does not cause DM in dogs, although carrying the SOD1 variant increases a dog’s chances of developing DM.
Only two SOD1 variants have been found in dogs. After testing DNA from nearly 34,000 dogs, Zeng et al. (2014) found one variant only in Bernese Mountain Dogs. But the other variant was in 124 of the 222 breeds tested. Importantly, how common the SOD1 variant was in a breed did not correlate with how often DM was diagnosed. The most glaring example is Wire Fox Terriers, where 71 of 79 dogs had two copies of the SOD1 variant, suggesting DM should be rampant in the breed. But it is not.
At present, the SOD1 variants in dogs are considered risk factors for developing DM, although having one or two copies of the SOD1 variant does not mean a dog will develop DM. Presumably there are other unidentified genetic risk factors in dogs, but we cannot be sure. There probably also are sporadic cases of DM in dogs, as with ALS in humans.
There were 38 Deerhounds in the samples tested by Zeng et al. None had a variant SOD1 gene. And yet, as I discussed at the beginning of this article, DM has been diagnosed in Deerhounds and may not be uncommon if a Deerhound lives long enough. This suggests that the SOD1 genetic test probably is unhelpful for evaluating DM risk in Deerhounds. Instead, DM in Deerhounds could be associated with a different genetic risk factor, or DM cases in our breed may simply be sporadic.
Research in patients with SOD1-variant ALS and dogs with SOD1-variant DM reveals that the motor neuron degeneration in both species is accompanied by the accumulation of clumps of the variant SOD1 protein. These clumps presumably contribute to the motor neuron degeneration in DM. To understand how they might do so, you need to learn a bit about motor neurons, how cells make proteins, oxygen’s dual nature, and SOD1 itself.
Motor neurons
Motor neurons are the longest cells in the body, some reaching more than 3 feet in a Deerhound. Stick a piece of chewing gum onto a countertop, pull a long strand out from it, and you have the shape of a motor neuron. The blob of gum is the cell’s body, where sits its “control center,” the nucleus. The long strand of gum projecting from the cell body is called an axon. A nerve sends a message by moving an electrical impulse from the cell body to the axon tip. At the tip, the impulse is passed along to another cell using a substance called a neurotransmitter.
A motor neuron makes its neurotransmitter in the cell body, but it stores and uses the neurotransmitter at the axon tip. The neurotransmitter reaches the tip by “axonal transport.” The semi-liquid contents of a motor neuron constantly circulate from the cel body to the axon tip and back again, just like blood circulates from the heart and back again. Axonal transport keeps the cell body in constant communication with the axon tip.
Figure of a spinal motor neuron, showing the cell body on the left and the axon reaching to innervate muscle fibers on the right. The myelin sheath is shown as it exists, as distinct short segments instead of a continuous sheath.
How cells make proteins
Proteins are long chains of amino acids. A cell’s DNA has the blueprint for making a protein, which spells out the sequence of amino acids. When a cell wants to make a protein, it transcribes a copy of the blueprint into a molecule called RNA. An intracellular factory called a ribosome then uses the RNA to put the right amino acids together in the right order. Basic biology classes leave protein-making there, with the protein looking like a strand of pearls. But that is only the beginning.
Some amino acids have positive or negative electrical charges. Like charges repel each other, while unlike charges attract each other, just like in a magnet. Once the protein is made, the charges cause it to bend and fold into a 3‑dimensional structure with projections and pockets. In addition, some amino acids in the protein may be modified by enzymes that add sugars, phosphate, or acetylate, a process called post-translational modification. On top of that, some larger proteins are composed of multiple amino acid chains, each of which is made separately. These subunits then are joined to make the final protein.
Any variation in the DNA blueprint for a protein can affect the protein that is made. Sometimes the change ruins the blueprint, so that the cell cannot make the protein at all. Sometimes the change just means that one of the amino acids in the protein is different. A change in a single amino acid can cause the protein to misfold, end up in the wrong location, work less effectively or not at all, or be unstable.
Oxygen’s dual nature
We all know that oxygen is the good guy, right? Well, yes and no. Animals do need oxygen to live, which plants steadily make as a byproduct of photosynthesis. Deprive an animal of oxygen, and it quickly dies. Many of us learn this lesson early in life, when the fireflies we capture in a jar on a summer night are all dead the next morning because we did not punch holes in the jar lid.
But like Anakin Skywalker and Dr. Jekyll, oxygen has a dark side. Oxygen is what chemists call a reactive element, meaning it likes to combine with just about anything it encounters, especially metal atoms. Build a steel bridge, and oxygen in the air will immediately start combining with the iron atoms in the bridge to form iron oxide, aka rust. Given time, oxygen will reduce the bridge to a pile of red-brown dust. This is why bridges are painted – to keep the iron out of oxygen’s reach.
The process of oxygen combining with a substance is called oxidation. A substance that has combined with oxygen is said to have been oxidized. A substance that slows or prevents oxidation (like the paint on the bridge) is called an antioxidant.
Unfortunately for living things, the carbohydrates, fats, proteins, and DNA that make up their cells and tissues also can be oxidized. Over time, the cumulative oxidative damage can kill the cell. Such oxidative damage (often called oxidative stress) is thought to underly or contribute to many chronic diseases in dogs and humans.
To survive, animals have evolved defense mechanisms. Their first strategy is to ensure that oxygen is always “chaperoned.” A chaperone is a molecule whose job is to curtail oxygen’s tendency to react with any molecule it encounters. One such chaperone is hemoglobin, the protein that makes red blood cells red. Hemoglobin contains an iron atom. Once oxygen reacts with the iron atom in hemoglobin, it is no longer free to react with another molecule. Chaperoned by hemoglobin, oxygen can be safely transported from the lungs to all the cells of an animal’s body. At the cell surface, oxygen is handed off to other chaperones within the cell. These, in turn, give oxygen to enzymes, which use it to generate energy and make the molecules that keep the cell alive and functioning.
Like teenagers at a high school dance, some oxygen atoms will escape their chaperones. Chemists give these unchaperoned oxygen atoms the wonderfully vivid name of “free radicals.” Like human radicals, oxygen radicals can sabotage a cell’s ability to function and even kill the cell. Biochemists refer to oxygen free radicals as “reactive oxygen species” (ROSs), as if they were an independent life form.
To cope with free radicals, cells have evolved other defense mechanisms, collectively called the antioxidant defense system. A common way that free radicals form is when oxygen reacts with a metal atom. To reduce the chances of this happening, animals make molecules that capture and hold (chelate) free metal atoms, so they are unavailable to react with oxygen. This is one of the main reasons that metals like lead, mercury, cadmium, and arsenic are poisonous – they accelerate formation of free radicals that overwhelm the antioxidant defense system.
Another part of the antioxidant defense system are compounds called free radical scavengers, which react with and neutralize free radicals. You will be familiar with some of these: vitamin C, vitamin E, beta-carotene (a vitamin A precursor), and a host of other compounds found in plant products like fruits, vegetables, tea, and wine. Besides all the antioxidants that come from plants, animal cells make their own free radical scavengers, such as uric acid, bilirubin, melatonin, and a peptide called glutathione.
Still another part of the antioxidant defense system are enzymes that convert a free radical into a less harmful substance. The most important of these enzymes belong to the SOD family. SODs convert a free radical into less harmful hydrogen peroxide, while two other enzyme systems – glutathione peroxidase and catalase – convert the hydrogen peroxide into harmless water.
SOD1 and ALS
At first, researchers thought that the variant SOD1 protein in ALS patients might be inactive, weakening the antioxidant defenses of spinal motor neurons, and that cumulative oxidative damage over decades caused those neurons to degenerate. Indeed, some variant SOD1 proteins are inactive. But others work just fine.
Then researchers discovered that the variant SOD1 proteins often misfold during post-translational modification. The misfolded SOD1 proteins tend to form clumps. These clumps are visible microscopically in the motor neurons of ALS patients. Sometimes the clumps even become self-propagating, much like the clumps of prion protein that cause Mad Cow disease. One theory is that the clumps interfere with axonal transport, gradually cutting off the cell body from the axon, which then withers and dies.
SOD1 and DM
As in many patients with SOD-1 variant ALS, the variant SOD1 protein in dogs with DM works properly but forms clumps in motor neurons (Crisp et al., 2013). These clumps are diagnostic for SOD1-variant DM. When Zeng et al. examined spinal cord samples from 115 dogs diagnosed with DM, they found SOD1 protein clumps in 114 of them. These clumps presumably lead to motor neuron degeneration by the same mechanism as in humans with SOD1-variant ALS.
Conclusions about DM in Deerhounds
I began this article by saying that the results of the 2011 Deerhound Health Survey show that DM occurs in Deerhounds. I pointed out that DM is hard to diagnose in life but can be diagnosed at necropsy by examining spinal cord samples. I also noted that this is rarely done unless the owner asks.
Recently, an owner who had to euthanize her 8‑year-old bitch DID ask that the spinal cord be examined microscopically. The bitch had a sudden onset of serious illness, but she was not suspected of having DM.
Spinal cord samples from 10 levels were examined. All had multiple areas of motor neuron degeneration. The thoracolumbar spinal cord was the most severely affected. The degeneration was characterized by vacuoles containing foamy macrophages or swollen axons and spheroid bodies. The pathologist remarked that these changes are highly suggestive of DM. This bitch also was tested for the SOD1 genetic variant, which she did NOT carry.
Clearly, this 8-year-old Deerhound had DM, which was discovered by accident after her death instead of being diagnosed in life. This dog’s DM was not due to a known SOD1 variant. This fits with the DNA screening results from Zheng et al., which tell us that the known SOD1 variants are not present in the Deerhound breed. For now, this case of DM must be considered sporadic.
Is a different genetic variant present in our breed that puts a Deerhound at risk of developing DM? Or is DM in Deerhounds sporadic, as in most ALS patients? Right now, we simply do not know.
References
Berdyński, M., Miszta, P., Safranow, K. et al. SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity. Sci Rep 12, 103 (2022). https://doi.org/10.1038/s41598-021-03891-8,
Crisp MJ, Beckett J, Coates JR, Miller TM. Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model. Exp Neurol. 2013 Oct;248:1-9. doi: 10.1016/j.expneurol.2013.05.009. Epub 2013 May 23. PMID: 23707216; PMCID: PMC3773294.
Zeng R, Coates JR, Johnson GC, et al. Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Intern Med. 2014 Mar-Apr;28(2):515-21. doi: 10.1111/jvim.12317. Epub 2014 Feb 13. PMID: 24524809; PMCID: PMC4238831.