Similarities between canine degenerative myelopathy and amyotrophic lateral sclerosis led to the finding of a mutation of the superoxide dismutase 1 (SOD1) protein in dogs with canine degenerative myelopathy (CDM).

Further research into the role of the SOD1 mutation in the development of CDM suggests that mutant SOD1 alone may not always result in disease expression. However, ongoing studies of the similarities between CDM and amyotrophic lateral sclerosis (ALS) may aid in understanding both diseases.

What is Canine Degenerative Myelopathy?

Canine degenerative myelopathy is a disease of the motor neurons, a group of nerve cells that originate in the brain and spinal cord and are involved in muscle control. Originally thought to be restricted to the lower motor neurons, it is now known that CDM affects both upper and lower motor neurons.

Canine degenerative myelopathy is, therefore, very similar to amyotrophic lateral sclerosis. Veterinary scientists attempting to find the genetic basis for this canine disorder turned to ALS research for clues. The SOD1 mutation had already been established as a factor in approximately 20% of the familial cases of ALS and in some sporadic cases as well.

What is Amyotrophic Lateral Sclerosis?

Amyotrophic Lateral Sclerosis is also a degenerative disease of both upper and lower motor neurons wherein the degeneration of those motor neurons results in weakness of the arms and legs and difficulty speaking, swallowing and breathing. ALS is also popularly known as Lou Gehrig’s Disease, after the famous baseball player who had ALS and thus brought it to the attention of the general public.

Similarities and Differences Between Amyotrophic Lateral Sclerosis and CDM

ALS and canine degenerative myelopathy both have symptoms of the progressive loss of muscle control, both involve both upper and lower motor neurons and a mid-adulthood onset. Definitive diagnosis is difficult in both cases. But there are differences.

Amyotrophic lateral sclerosis is 20% more common in men than women and the sporadic form, which is not inherited, accounts for the majority of the cases (90–95%). The familial form, in which the defective SOD1 gene is present, is much less common, possibly indicating an environmental component to the development of this disease.

The finding that military personnel, particularly Gulf War veterans, are twice as likely to develop sporadic amyotrophic lateral sclerosis further bolsters the environmental component theory in ALS. In addition there was a high incidence of ALS in the Trust Territories of the Pacific and Guam during the 1950s.

In dogs, canine degenerative myelopathy is most often familial, with some breeds showing a high predisposition to the disease. Over 100 breeds of dog have been found to have the mutated SOD1 protein and, unlike ALS, the condition occurs equally in males and females.

To date, the use of a recently developed test for CDM has shown that all affected dogs have inherited the SOD1 protein mutation from both parents, but not all dogs with double mutations have developed symptoms. And thus far, no dogs that have tested clear (two normal SOD1s) or carrier (one normal, one mutated) have developed symptoms.

It is not yet clear whether this indicates other factors are involved in the expression of the disease but a May 2011 study found evidence of oxidative stress in the spinal lesions of the DM-affected dogs. However, no SOD1-positive inclusion bodies were found within the motor neurons, raising further questions regarding the exact role of SOD1 in canine degenerative myelopathy.

Comparing Amyotrophic Lateral Sclerosis and CDM

These differences between Amyotrophic Lateral Sclerosis and Canine Degenerative Myelopathy means that the comparisons between the two conditions must be viewed with some caution. It seems in both cases that there is more involved than one genetic mutation. But the lack of expression of CDM in dogs that have tested clear or carrier does give dog breeders an important tool in reducing the incidence of the disease.

Sources:

Awano, T. et al. 2009. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences. 106 (8) 2794-2799.Ogawa, M. et al. 2011.

Imunohistochemical observation of canine degenerative myelopathy in two Pembroke welsh corgi dogs. J Vet Med Sci. Online ISSN: 1347-7439. accessed 6.30.11

The ALS Association. Accessed online 6.26.11

First published in 2011