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Taylor C Parker, Joan R Coates, DVM, and John R Parker, MD

Canine Degenerative Myelopathy, also referred to as CDM or DM, is a disease affecting

the nervous system of many breeds both large and small. Classically affecting the spinal cord,

the degeneration progresses causing loss of limb function from hind to front limbs (Averill 1973,

Coates and Wininger 2010). Based on the SOD1 gene mutation the disease has many similarities

to Amyotrophic Lateral Sclerosis, also known as Lou Gehring’s Disease, a degenerative

neurologic disease present in humans (Awano et al. 2009). Canine DM can serve as a model for

ALS. With DM now being recognized as an important disease affecting dogs of many breeds, it

is important to understand the cause to limit its genetic spread in future generations of dogs

(Fiszdon et al. 2020).

There is no gender predisposition in DM, but age has a role as DM typically affects dogs

in the later stages of their lives, around the age of 9 years in large dogs and 11 years in smaller

breeds like the Pembroke Welsh Corgi (Coates et al. 2007). The earliest clinical signs include

incoordination and hindlimb weakness (Averill 1973, Coates and Wininger 2010). General

proprioceptive ataxia refers to a dog’s inability to recognize limb position and posture, and this

symptom is also characteristic of DM. As the disease progresses, the dog loses fecal and

urination control, along with losing muscle mass and limb strength. If the dog becomes

paraplegic and is not euthanized, the weakness ascends to the forelimbs and eventually the dog

becomes tetraplegic (Coates and Wininger 2010). Once the disease reaches the dog’s brain, the

dog will struggle to even swallow or bark, and the condition is terminal with respiratory failure

(Awano et al. 2009, Coates and Wininger 2010, Ogawa et al. 2013).

The main cause of DM is genetic with a mutation in the SOD1 gene ( SOD1 ) (Awano et

al. 2009). This stands for superoxide dismutase (SOD), and the 1 refers to the version of this

enzyme found in the cytoplasm of the cell. When this gene is not copied correctly, or mutates, it

can cause changes in the proteins that are coded by the gene, and these changes can in turn result

in cell death, specifically of neurons and supporting cells (Fiszdon et al. 2020). For dogs with the

mutated version of the gene, homozygous recessive individuals have the greatest risk of disease

while heterozygous individuals have a decreased risk of DM. Homozygous refers to an organism

having two copies of the mutated allele for the same version of a gene, while heterozygous refers

to an organism having one mutated allele. While the presence of a mutated allele can indicate a

likelihood of disease, there may be other genes or modifying genes that may also result in the

disease phenotype or expressed trait. Additionally, not all homozygotes develop clinical disease,

so the presence of the mutated allele indicates a risk for developing DM (Coates and Wininger

2010, Fiszdon et al. 2020).

In light of the genetic factors involved in DM, genetic testing has become a point of

interest in its study. Genetic testing will complement other antemortem diagnostics for DM.

Most DM-affected dogs are homozygous for the mutant allele . Thus, homozygosity for the

mutant SOD1 allele is a major risk factor for canine DM. However, many dogs homozygous for

this mutation do not develop clinical signs. The age at onset for many dogs has exceeded the

mean life expectancy of dogs indicating that DM has an age-related, incomplete penetrance

mode of inheritance. DM has also been histopathologically confirmed in few heterozygous dogs

of certain breeds (Zeng et al. 2014). The occurrence of DM in a heterozygote seems plausible

since most human SOD1 mutations cause dominant ALS.

A second SOD1 mutation that was homozygous in an affected Bernese Mountain dog

was identified, and this mutant allele appears to be restricted to the Bernese Mountain Dog

breed, where it is less common than the first mutant allele described. Affected homozygotes in

other breeds have not yet been discovered. This finding serves as a reminder that direct DNA

tests indicate the presence or absence of disease-causing alleles but cannot be used to rule-out a

diagnosis because other sequence variants in the same gene or in a different gene might produce

a similar disease phenotype (Wininger et al. 2012).

As a result of this ambiguity, the diagnosis of DM is generally one of exclusion, meaning

that other diseases must be ruled out first before DM can be diagnosed with certainty. Generally,

differential diagnoses include intervertebral disc herniation, cancer of the spine or spinal cord,

and other mimicking compressive spinal cord diseases. These may be ruled out by imaging

methods such as spinal cord magnetic resonance imaging (MRI). An important step in obtaining

an appropriate diagnosis is to have a dog with clinical signs be evaluated by a board-certified

veterinary neurologist ( ; then go to find a specialist ). Signs of orthopedic disease

can be confused with neurologic diseases. A proprioceptive placement test, where the foot is

placed such that the paw is positioned knuckled over, is an important diagnostic tool. If the dog

can quickly recognize that its foot has been mispositioned, then the signs of limb dysfunction

may be orthopedic. DM can only be definitively diagnosed by histopathology of the spinal cord,

which is performed by autopsy examination (Coates and Wininger 2010). DM is characterized

by degeneration of the axons (processes carrying electrical transmission) and secondary loss of

the myelin sheaths (insulation) that wrap around the axons. Another key feature is astroglial

proliferation, which is most severe in the lateral and dorsal columns (Averill 1973, March et al.

2009). Neuron loss occurs in terminal disease (Ogawa et al. 2014). A veterinary pathologist is

able to discern these characteristics on a post mortem examination to establish a diagnosis of DM

(Coates and Wininger 2010).

Physical rehabilitation may improve the dog’s quality of life as the disease progresses.

Dogs who received physiotherapy survived longer on average than those who did not, an average

of 255 days and 55 days respectively, and these passive and active exercises were tailored to the

dog’s disease progression (Kathmann et al. 2006). Studies surrounding the impact of diet have

been performed, but it was concluded that there is no definitive evidence of improvement over

the treatment of physical therapy alone. Caution must be taken when facilitating any sort of

exercise therapy as the already weakened muscles can be easily damaged and fatigued, which

may increase the rate of disease progression (Polizopoulou et al. 2008).

In connection to research surrounding the human disease ALS, therapeutic models are

being investigated in dogs. Since the SOD1 mutation is important in both ALS and DM, canine

DM serves as a model for disease translation (Awano et al. 2009, Fiszdon et al. 2020). As a

result, studies are being conducted surrounding silencing the SOD1 gene and observing its effect

on the mobility of dogs affected with DM (Story et al. 2020). While these studies are in their

early stages, there is a possibility of successfully applying a canine disease model to ALS, with

benefits for both humans suffering from ALS and dogs suffering from DM (Coates and Wininger


Since there are currently no effective treatments for DM, breeders perform genetic testing

to mitigate transmission of the risk mutation to offspring. If a risk factor for DM is discovered

early, it allows the owner to be more responsible in the management of their breeding program.

Since the mutant allele is known to be present in over 180 purebred and mixed breeds, it is

important to be aware of its wide presence in the canine population. Research to find treatments

and study DM is being led by Dr. Joan R. Coates at the University of Missouri Veterinary Health

Center and other researchers worldwide. Laboratories are studying ways to diagnose and

measure disease progression with similar diagnostic modalities used in ALS patients. The

diseased tissues also are studied at all stages of progression. The nervous system tissue may be

harvested after the dog’s death by a necropsy (Coates and Wininger 2010). Spinal cord tissue

will also be retained for research purposes for other DM and ALS researchers in hopes of

understanding the molecular and genetic spectrum of this disease. The first step is to

characterize and document canine DM in the Mastiff.

Key References:

Averill DJ. (1973) Degenerative myelopathy in the aging German Shepherd dog: clinical and

pathologic findings. J Am Vet Med Assoc 162:1045-1051.

Awano T, Johnson GS, Wade C, Katz ML, et al. (2009) Genome-wide association analysis

reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic

lateral sclerosis. Proc Natl Acad Sci U S A 106:2794-2799.

Coates JR, March PA, Ogelsbee M, et al. (2007) Clinical characterization of a familial

degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med


Coates JR, Wininger FA. (2010) Canine degenerative myelopathy. Vet Clin North Am Small


Pract 40:929-950.

Fiszdon K, Gruszcynska J, Siewruk K. (2020) Canine Degenerative Myelopathy – pathogenesis,

current diagnostics possibilities and breeding implications regarding genetic testing. Acta

Sci. Pol. Zootechnica 19(1): 3-10.

Kathmann I, Cizinauskas S, Doherr MG, et al. (2006) Daily controlled physiotherapy increases

survival time in dogs with suspected degenerative myelopathy. J Vet Intern Med


March PA, Coates JR, Abyad R, et al. (2009) Degenerative myelopathy in 18 Pembroke Welsh

corgi dogs. Vet Pathol 49:241-250.

Morgan BR, Coates JR, Johnson GC, Bujnak AC, Katz ML. (2013) Characterization of

Intercostal Muscle Pathology in Canine Degenerative Myelopathy: A Disease Model for

Amyotrophic Lateral Sclerosis. J Neurosci Res 91:1639–1650.

Morgan BR, Coates JR, Johnson GC, Shelton GD, Katz ML. (2014) Characterization of

Thoracic Motor and Sensory Neurons and Spinal Nerve Roots in Canine Degenerative

Myelopathy, a Potential Disease Model of Amyotrophic Lateral Sclerosis. J Neurosci

Res . 92: 531–541.

Polizopoulou ZS, Koutinas AF, Patsikas MN, et al. (2008) Evaluation of a proposed therapeutic

protocol in 12 dogs with tentative degenerative myelopathy. Acta Vet Hung. 56(3):


Ogawa M, Uchida K, Yamato O, et al. (2013) Neuronal Loss and Decreased GLT-1 Expression

Observed in the Spinal Cord of Pembroke Welsh Corgi Dogs With Canine Degenerative

Myelopathy. Vet Path 51(3):591-602.

Story BD, Miller ME, Bradbury AM, et al. (2020) Canine Models of Inherited Musculoskeletal

and Neurodegenerative Diseases. Front. Vet. Sci. 7: 80.

Wininger FA, Zeng R, Johnson GS, et al. Degenerative myelopathy in a Bernese mountain dog

with a novel SOD1 missense mutation. J Vet Intern Med 2011;25:1166-1170.

Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, et al. (2014) Breed

Distribution of SOD1 Alleles Previously Associated with Canine Degenerative

Myelopathy J Vet Intern Med 28:515.

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