Baseball’s pitchers and catchers reported for spring training in February, and the American love affair with our national pastime began anew this spring.
But a new season brings a time for reflection on seasons past, and for many, that conjures up memories of some of the game’s most iconic players. Lou Gehrig is considered one of the greatest players the sport has ever seen, but his name is more frequently linked to one of its saddest chapters: Gehrig’s brilliant career was tragically cut short by the debilitating neurological disease amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig’s disease.
Now, thanks to creative researchers and pet dogs, scientists are studying a genetically related canine disease, degenerative myelopathy (DM), to help advance medical knowledge and pioneer treatments for both disorders.
Sidelined by Disease
The basis for the study of canine degenerative myelopathy as a model for human ALS research began 14,000 years ago with the domestication of the dog. Fast-forward to Victorian times when selective breeding created the modern breeds we know today. Each of these “purebreds” was developed for a specific function: herding sheep, retrieving game or controlling vermin. While selective breeding practices propagated desirable traits such as intelligence, tenacity and waterproof coats, “bad” genes predisposing dogs to disease tagged along with the good ones, leading to some of the breed-linked diseases that we see and study today.
Veterinarians initially believed degenerative myelopathy was a disease limited to the German Shepherd breed and that it only affected the hind limbs. Additional research, however, has shown that this disease also affects such diverse breeds as the sturdy Boxer, the low-slung Pembroke Welsh Corgi, the fearless Rhodesian Ridgeback and the waterproof Chesapeake Bay Retriever.
Everyone has probably seen a dog affected by degenerative myelopathy in the dog park or on the street. Dogs with DM drag their back paws and wobble in the hind end but are otherwise pain free and enjoy playtime with their human companions.
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As with ALS, a diagnosis of DM is heartbreaking for the patient’s family. Degenerative myelopathy strikes dogs in the prime of life and progresses rapidly. Most dogs become paraplegic within a year of onset of clinical signs. Small dogs who are more easily cared for after they lose hind limb function will continue to deteriorate until, similar to ALS patients, they become quadriplegic. Relentless progression of the disease robs dogs of the ability to control their bowels and bladder and, in severely affected dogs, the ability to swallow or bark.
A Genetic Curveball
In 2004, the final piece of the puzzle that helped sniff out the root cause of degenerative myelopathy fell into place with the sequencing of the canine genome.
Coupled with extensive canine family trees maintained by purebred dog enthusiasts such as the American Kennel Club, the canine genome can now be analyzed for clues to the cause of — and potential new treatments for — degenerative myelopathy and related disorders like ALS.
One of the recent big wins for biomedical research was the identification of a genetic mutation associated with degenerative myelopathy in dogs. Veterinarians at the University of Missouri knew degenerative myelopathy ran in the Pembroke Welsh Corgi breed, and their early investigations focused on a potential genetic cause. They assembled a team of multidisciplinary researchers from their own institution as well as Columbia University, Uppsala University in Sweden and The Broad Institute at MIT.
In 2009, this team identified a genetic mutation in the Corgis in the same gene that physicians knew was important in inherited forms of ALS in humans. In dogs, a one-molecule swap in the genetic code for superoxide dismutase one (SOD-1) changed the structure of a protein found in the nervous system. This tiny error is a game changer and places dogs with the defect in a high-risk group for the development of degenerative myelopathy.
Studying the Stats
Shortly after discovery of the mutated SOD-1 gene in Pembroke Welsh Corgis, a genetic test for the mutation was developed. For the first time, veterinarians treating dogs with neurologic diseases could determine which of their canine patients were at high risk for developing degenerative myelopathy, and they could use that information to form their diagnostic and therapeutic plans. The test can also help identify dogs likely to develop clinical signs of DM, allowing breeders to carefully choose animals for breeding programs.
The test for the degenerative myelopathy gene can be performed on a blood sample obtained in a veterinarian’s office or on cheek cells collected by the owner on a swab. Information published as an Early View online open-access article in the Journal of Veterinary Internal Medicine reports on the use of this test in nearly 35,000 dogs. More than 120 different breeds and mixed breed dogs were found to have the exact same genetic error found in the Pembroke Welsh Corgis in the Missouri-led study.
Dr. Joan Coates, a diplomate of the American College of Veterinary Internal Medicine (neurology specialty), professor of veterinary medicine at Missouri University and a member of the research team involved in the groundbreaking study, says, “The widespread distribution of the SOD-1 gene mutation throughout the pet dog population means veterinarians and dog owners alike cannot have tunnel vision when working with dogs suspected to have degenerative myelopathy.” There are most likely breed differences for susceptibility of this risk factor.
Dr. Coates further points out, “Since the mutation test evaluates for a risk factor, many dogs will have a positive test for the degenerative myelopathy gene but not necessarily have the disease. In its early stages, degenerative myelopathy and, for that matter, ALS can look like a slipped disk, a disease which is far more common in the dog than degenerative myelopathy.” Dr. Coates recommends consultation with a board-certified veterinary neurologist in order to arrive at an accurate diagnosis.
Early diagnosis of degenerative myelopathy is imperative as the implications of the disease are dire. The dog could also have a different but treatable disease.
Dogs as Disease MVPs
Dogs with degenerative myelopathy are quickly becoming the leadoff “batters” on the clinical trials team. Using canine DM patients in studies can allow for an evaluation of investigational therapies in a naturally occurring model of ALS and ultimately lead to initiation of human clinical trials. Backed by funding from the National Institutes of Health and the ALS Association, investigations into drug therapy for dogs with DM are now in early phases. The drugs, currently undergoing safety testing prior to full-scale evaluation in pet dogs with degenerative myelopathy, block production of the abnormal protein in the nervous system that leads to this disease.
The advanced neurologic system of dogs combined with their high cognitive ability and similar home environment better mimics the human condition. Knowledge gained from upcoming studies for the treatment of degenerative myelopathy in dogs will hopefully also lead to more effective treatment of ALS in humans.
In short, man’s best friend is on base and looking to score the winning run in a scientific competition where dogs and humans will both be winners.
Diana Ruth Davidson, Chief Pet Officer and Managing Nanny, Westside Dog Nanny
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