Dogs and humans could benefit from potential new therapies and diagnostic techniques for a degenerative neurological disease
By Kim Campbell Thornton
Andrews McMeel Syndication
New therapies and diagnostic tests have the potential to help dogs with a progressive neurodegenerative disease live longer lives. Boxers, German shepherds and Pembroke Welsh corgis are among more than 100 breeds and mixes that may benefit from two therapies being studied, as well as a diagnostic biomarker test for degenerative myelopathy, a disease of the central nervous system that develops late in life.
The condition, which typically affects dogs between 8 and 14 years old, damages the spinal cord, muscles, nerves and brain, causing loss of muscle control, weakness in the hind legs and, eventually, paralysis. Dogs with two copies of a mutation in the gene superoxide dismutase 1 (SOD1) are at risk for the disease, but not all dogs with the mutation will develop the disease.
Early signs include dragging or shuffling the hind legs. At first, owners may suspect the weakness or lameness is caused by an orthopedic condition or simply advancing age, says Dominik Faissler, DVM, assistant professor of neurology at Tufts Cummings School of Veterinary Medicine in North Grafton, Massachusetts.
As the disease progresses, the dog may stumble and fall, have difficulty standing up and lose mobility as the nervous system becomes unable to transmit motor commands between brain and limbs. Gradually, the brain stem becomes affected, causing difficulty swallowing. Paralysis usually occurs in the space of a year. Most dogs are euthanized before they develop difficulty breathing, Dr. Faissler says.
Currently, a DNA test developed in 2009 is available to identify the recessive gene mutation that causes the disease, allowing breeders to avoid producing affected dogs, but last year’s discovery of a diagnostic biomarker can help lead to earlier diagnosis of dogs at risk of developing DM, as it’s called for short. It’s also important for researchers in human medicine who study amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease. The same mutation that causes DM in dogs also causes ALS in humans.
Finding the biomarker involves collecting cerebrospinal fluid from the affected dog. That’s more difficult and expensive than a blood test because it requires anesthesia, but less expensive than magnetic resonance imaging (MRI). Because DM mimics other diseases such as intervertebral disc disease and spinal cancer, an MRI is part of the process to rule out those conditions. Even then, the diagnosis is not considered definitive until the dog dies and a necropsy is performed. As the biomarker test becomes more widely available, it may help to provide earlier and more reliable diagnoses. And earlier diagnosis goes hand in paw with the search for effective therapies.
One of the therapies being studied involves injecting antisense oligonucleotides (ASOs) into the spinal fluid with the goal of suppressing production of the mutant protein SOD1. Researchers hope the molecular therapy will be able to sneak past the blood-brain barrier and “silence” the messenger RNA, slowing or stopping disease progression. Affected dogs who meet certain criteria may be eligible to participate in the study, conducted at the University of Missouri. A gene-silencing study is also under way at Tufts Cummings School.
A gene therapy clinical trial, also at the University of Missouri, injects what’s called interference RNA (iRNA) into the spinal fluid to repress production of the SOD1 protein. Dogs in the early stages of the disease may also be eligible to participate in that study.
Both University of Missouri studies are randomized and double-blinded. That means neither researchers nor owners know which dogs receive the treatment and which receive a placebo. The study’s design gives dogs a 67 percent chance of receiving the treatment, according to the university’s website.
The treatments have been tested for safety, but their effectiveness isn’t yet known. The same therapeutic approach is being studied in humans with SOD1-associated ALS. Success in either dogs or humans will likely benefit both.