Few illnesses are more devastating to patients and their families than amyotrophic lateral sclerosis, a incurable progressive neurodegenerative disease that affects some 5,600 Americans each year.
Commonly referred to as Lou Gehrig’s disease — the Yankee ironman’s Hall-of-Fame career was tragically cut short by the condition in 1939 — amyotrophic lateral sclerosis, or ALS, attacks nerve cells and pathways in the brain and spinal cord. Patients in the later stages of ALS typically lose all voluntary muscle control, even as their minds remain sharp and alert. Most, according to the ALS Association, survive no more than five years after their diagnosis.
Researchers have for some time known the onset of ALS can be related to a defective gene called SOD1. They have, accordingly, developed research models based on mice and rats genetically engineered to produce a defective version of that gene. Unfortunately, the value of these transgenic rodents is diminished by the sheer volume of the often SOD1 they produce, so much that they may develop pathologies by mechanisms distinct from those occurring in human ALS patients.
A new finding by scientists at the MU College of Veterinary Medicine offers promise of a less problematic model. The discovery, published in the Feb. 24, 2009, edition of the Proceedings of the National Academy of Sciences, has for the first time demonstrated that a genetic mutation responsible for an ALS-like condition in dogs, degenerative myelopathy, is related to an SOD1 mutation similar to mutations in Lou Gehrig’s disease. Principal investigator Joan Coates, a veterinary neurologist and associate professor in MU's Department of Veterinary Medicine and Surgery, says the discovery will likely be a boon to scientists working to help both dogs and people combat these terrifying maladies.
“Dogs with DM are likely to provide scientists with a more reliable animal model for ALS. Also, this discovery will pave the way for DNA tests that will aid dog breeders in avoiding DM in the future,” says Coates.
Like ALS, DM leads to advancing weakness and muscle atrophy culminating in paralysis. The condition was initially reported in German Shepherd Dogs, but has since been identified in other breeds such as Cardigan and Pembroke Welsh Corgis, Rhodesian Ridgebacks, Chesapeake Bay Retrievers and Boxers. No treatments have been shown to stop DM's progression.
Since the SOD1 mutation is spontaneous in canines, pathogenesis in dogs may more accurately mirror that of human ALS, says Coates’ colleague and study collaborator Gary Johnson, an MU associate professor with MU's Department of Veterinary Pathobiology. He says dogs provide other advantages as well: “Compared with the rodent models for ALS, dogs with DM are more similar to people in size, structure and complexity of their nervous systems, and duration of the disease. The results from clinical trials conducted with DM-affected dogs may better predict the efficacies of therapeutic interventions for treating ALS in humans.”
The study, “Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy which resembles amyotrophic lateral sclerosis,” was a collaborative project among MU's researchers and Kerstin Lindblad-Toh and Claire Wade, researchers at the Broad Institute of the Massachusetts Institute of Technology and Harvard. The study was funded by the American Kennel Club Canine Health Foundation and clubs representing several of the canine breeds most at risk from the disease.