Stem-Cell Therapy May Benefit Dogs With Intervertebral Disc Disease
A devoted Cocker Spaniel enthusiast, Beverly Tucker knew right away something was wrong when her adopted dog, “Tobi,” yelped while playing in the yard with other dogs. Though it was dinnertime, the 4-year-old mixed-breed Cocker Spaniel had no appetite, and he dragged his rear as he tried to walk. Within half an hour, the dog had lost the use of his hind legs.
Tucker and her husband, John, of Thomasville, N.C., rushed Tobi to an emergency veterinary clinic, where the dog received cortisone to help relieve swelling around his spinal cord. Instead of improving, Tobi began to lose deep pain sensation in his hind end. Referred to a veterinary neurologist, the Tuckers learned that Tobi suffered from intervertebral disc disease (IVDD), a degenerative disc disorder. The neurologist recommended surgery to decompress the pressure on Tobi’s spine, although the chance of recovery was about 50 percent.
“The veterinarian told us that if the surgery wasn’t successful, it was likely that Tobi would be paralyzed from his waist down,” Tucker says.
Cocker Spaniels and other breeds that are genetically predisposed to IVDD develop Type I disease. A sudden, large tear in the degenerated, weak outer layer of the disc causes the degenerated, hard center to explode into the spinal column.
Other chondrodystrophoid breeds prone to IVDD are: Dachshund, Pekingese, Lhasa Apso, Shih Tzu, Basset Hound, Beagle, Poodle, and Pembroke and Cardigan Welsh Corgis. These long-backed, short-legged dogs classically develop signs of IVDD from 4 to 6 years of age, although it can occur anytime from 2 years of age and older.
Unfortunately, the surgery did not improve Tobi’s condition. The dog was unable to feel pain in his hind end, much less use his back legs. Tucker had two choices: to euthanize the dog or buy a cart to support his rear and learn to care for a paraplegic pet. Tucker resolved to learn all she could about IVDD to help Tobi.
An Internet search led Tucker to a clinical trial under way at North Carolina State University College of Veterinary Medicine to study stem-cell treatment options for dogs with spinal cord injuries. The three-year trial, directed by Natasha Olby, VetMB, Ph.D., DACVIM, professor of neurology, is funded by the Morris Animal Foundation with support from the American Spaniel Foundation.
Tucker received approval for Tobi to take part in the study. Though there was no cost to participate, the Tuckers paid to transport their dog to Raleigh, N.C., for treatments and evaluations.
The clinical trial at North Carolina State University involves evaluation of three therapies in paraplegic dogs with Grade 5 injuries, which are considered the worst cases. The participating dogs have complete paralysis with a lack of sensation to their hind limbs. The study is open to dogs regardless whether they received prior treatment.
Surgery is the most common treatment for spinal cord injuries and diseases such as IVDD. Without surgical intervention, the most severely affected dogs have less than a 5 percent chance of recovery. Those that have surgery within 24 hours — like Tobi — have only a 50-percent chance of recovery.
“The standard treatment involves surgically decompressing the spinal cord,” Olby says. “If improvement occurs, it normally starts within two weeks after surgery and then continues for weeks to months.”
There are varying degrees of severity of spinal cord injuries. The spinal cord is composed of neurons, or nerve cells. Deep within the spinal cord are pain-perception neurons. Dogs with severe injuries suffer loss of motor control and pain perception as well as bladder function.
Discs function as cushions between the spine’s bony vertebrae. They have two layers. An outer shell of collagenous tissue contains a soft center that absorbs stress on the spine. When a disc degenerates, it may compress the spinal cord over time and lead to gradual loss of neurological function, or it may be subject to concussive force with a sudden onset of loss of function and other neurological signs.
Olby’s study, currently in the first year, involves evaluation of 30 paraplegic dogs following one of three treatments. She is recruiting 10 dogs a year. Five small-breed dogs, including Tobi, have been treated thus far.
The treatments are:
- Injection of stem cells and Schwann cells into the spinal cord injury site coupled with an infusion of inosine, a substance with neuroprotective properties. The cells are suspended in an artificial cerebrospinal fluid (CSF) that contains nutrients to help support the cells.
- Inosine infusion only
- Injection of artificial CSF only
Culturing Adult Stem Cells
Stem cells have the ability to rapidly multiply and to take on the function of specialized cells by assimilating various functions. Stromal, or adult, stem cells are used in the study. Olby takes a sample of adipose, or fat, tissue and sensory nerves from the back of a dog’s neck from which stem cells and Schwann cells are cultured.
These adult fat-derived stem cells are cultured to produce neural stem cells. The Schwann cells produce myelin, a fatty substance that helps to insulate the nerves and allows them to conduct messages, in peripheral nerves. The therapy involves injecting the combination of stem cells and Schwann cells directly into the injured area in the spine. Because stem cells are autologous cells taken from the patient, there is no need for immunosuppressants to prevent rejection.
While some stem-cell therapy research involves using embryonic stem cells, this type of stem cell is associated with some risks. “The risk in using embryonic stem cells is that they will continue to divide and could develop into cancer,” Olby explains. “We use stromal cells because they divide a limited number of times and the risk of uncontrolled growth is much lower.”
Before treatment begins, dogs are evaluated once a week for one month to determine their baseline function. The dogs — most use paraplegic carts for mobility — are videotaped on a treadmill or walking outside.
“Dogs have good days and not-so-good days, so we do four separate evaluations,” Olby says.
After observing the dog’s movement, Olby uses magnetic resonance imaging to visualize the spinal cord and the exact location of the injury. Nerve conduction studies evaluate the conduction of impulses up and down the spinal cord. Dogs are then randomly assigned to one of the three treatment groups.
Olby hopes to see improvement in the dogs that receive stem-cell therapy that will lead to a new treatment for paralyzed dogs. In order to benefit dogs, the therapy must generate new cells to do the work of damaged ones. When the spinal cord is injured, the axons, or nerve fibers, that send messages along the spinal cord are damaged, affecting the transmission of signals from the brain to the body below the injury.
“While it would be ideal to regrow axons that have been disrupted, this goal is still out of reach because of the scarring that occurs following injury as well as the long distances over which the axons would have to regrow,” Olby explains. “However, axons are covered with a protective myelin sheath and after a severe spinal cord injury, it is common for some axons to survive but to lose their myelin sheath and thus their ability to conduct messages.”
The objective of adipose stem-cell therapy is to re-myelinate the surviving nerve cells and enable them to function again. If the treatment is successful, dogs may regain some use of paralyzed limbs and improved bladder control.
Tracking the Results of Treatment
After treatment, the dogs are evaluated and videotaped monthly for six months. The pre- and post-treatment videotapes are compared by blinded observers to assess changes in a dog’s ability. At the completion of the study, dogs that did not receive the stem-cell treatment are offered the therapy free of charge.
“It’s still early. We’ve only treated five dogs, and the scoring of their function will be done by blinded observers to allow objective assessment of the effectiveness of the treatments, but we are seeing promising results,” Olby says.
Though Tobi still uses a cart to go outside and to stand up when eating, Tucker is pleased with the results of his treatment. “He can move his legs more and can push his feet forward a little,” she says. “Otherwise, he moves by propelling himself forward with his front legs while trying to pull his hind legs under himself.”
The success of Tobi’s treatment is noted in his two-time participation in Canine Paralympics, an event sponsored by the North Carolina State University College of Veterinary Medicine. Last year, Tobi placed first in the obstacle course. Photos from the event show a cheerful dog wearing a red bandana.
The Tuckers hope that Olby’s research will help other dogs with IVDD and spinal cord injuries and ultimately people. Olby is collaborating with human researchers at other institutions, thus her research on dogs may indeed one day translate to new therapies for people.
Though there were no direct fees to participate in the stem-cell therapy, the Tuckers estimate they have spent more than $10,000 treating Tobi since he was first diagnosed with IVDD. Before they discovered Olby and her stem-cell therapy study, Tobi was treated at two facilities, where he received electronic stimuli to his muscles and water therapy.
“We have two other dogs that are rescues, and we love them all,” Tucker says. “We are so pleased with Tobi’s progress. We hope that what Dr. Olby learns from treating our special dog can help others with spinal cord injuries.”
Purina appreciates the support of the American Spaniel Club and particularly Karen Yager, Ph.D., the grants chair and member of the Board of Directors of the ASC Foundation, in helping to identify topics for the Purina Pro Club Cocker Spaniel Update newsletter.