Man’s Best Friend Comes to His Rescue Again
Posted May 26, 2012
University of Missouri researchers have uncovered the fundamental cause of degenerative myelopathy (DM), a debilitating muscular disease in dogs. This discovery may help them make strides towards discovering a cure.
After discovering the genetic mutation in 2009 that causes DM, MU scientists working with the College of Veterinary Medicine, School of Medicine and Christopher S. Bond Life Sciences Center have contemplated that this disease may also serve as a good model for understanding Lou Gehrig’s disease, also known as Amyotrophic Lateral Sclerosis (ALS), in humans. Both diseases are strikingly similar, both genetically and in their progression.
“It’s like, the thoracic cord isn’t happy, but do the motor units that are coming from that region look just as bad?” said graduate student Brandie Morgan about the starting question she used in having a better understanding of DM.
DM is an impactful genetic disease in dogs. The animals slowly lose function in their hind legs. Before long, the disease migrates into the dog’s forelimbs. There has not been much work done on understanding how the organs in the chest cavity may be affected by the disease. Symptoms typically occur when the dog is upwards of eight years old and will eventually causes paralysis.
To break down the disease, Morgan examined the nerves and muscles of affected dogs and compared them to healthy dogs of the same breeds. She found a different pattern of muscle fibers. Those of healthy dogs are uniform and have a “checkered” look, while the dogs with DM have muscle fibers that are more variable in size, and maybe similar to ALS, since the muscle fibers lose the nerve connections that control them. In order to eliminate variation between breeds, the muscle fibers were compared in both a Boxer and a Pembroke Welsh Corgi, which are both breeds commonly affected by the disease.
“The disease more likely starts in the cell body. As a result the nerve terminals are not getting their nourishment, so it has ‘dying back’ pathology since the nerve dies back from muscle to cell body,” said Morgan. Her research shows that there is no loss of neurons in the middle, thoracic region, of the spinal cord in the dogs with DM. This is also thought to happen in patients with ALS.
The study’s lead researcher, Dr. Joan Coates of the MU vet school, and various collaborators discovered the genetic mutation that causes DM in 2008. Previously, DM was considered to be a spinal-cord malady, and, in a sense, Morgan’s work is helping to re-write our understanding of the pathology of the disease in order to find more appropriate therapies.
As Morgan’s research continues to prove the relation of DM to ALS, her fundamental research of DM can be beneficial in relating this knowledge to owners of pets with that disease. “The thought is to find out as much as we can of what’s happening in DM, period,” says Morgan.
The difference between their research and other efforts to study ALS is that the MU researchers propose using dogs instead of mice, which hasn’t yet purposed effective drug therapies for ALS. Studying DM is much harder than studying lab mice, but is more useful for the fact that owners euthanize their dogs at various stages of the disease, which gives researchers a snapshot of the progression of DM, and maybe ALS.
The dogs that have been studied have a more similar physiology to humans than mice in their nerve complexity and muscle size. “Mice are good for understanding the disease process, but as far as curing anything, dogs would be a good model,” Morgan said.
In proceeding with this research, Coates’s team plans on repeating motor neuron counting in the Corgis, since they have only done such with Boxers. They hope to prove that not losing neurons in the thoracic spinal cord occurs in more than the one particular breed. Also, they plan on trying out an antibody on disease tissue of the dogs with DM to see if it helps in bringing the strength of the muscle fibers back to normal.
Though there is more work to be done, Coates and her team have taken a fundamental step in the direction of being able to treat DM in dogs, and along the way, they may find new clues for the treatment of ALS in humans. “ALS is just a really bad disease. It’s terrible how it just takes a toll on not just the patient, but also the family members,” said Morgan.