Treatment of Canine Paralysis with Autologous Adipose Tissue Derived Stem Cells, Schwann Cells & Inosine: A Blinded, Placebo Controlled Clinical Trial
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Sponsored by Morris Animal Foundation
Principal Investigator: Natasha Olby, Vet MB, PhD, DAVCIM
Co-Investigator and Study Coordinator: Ji-Hey Lim, DVM, PhD
Acute spinal cord injuries are a common problem in dogs, and due to the poor regenerative capacity of the nervous system, some dogs fail to recover and are left permanently paralyzed and incontinent. Experimental studies suggest that transplantation of several different types of neural cell can restore some neurological function in a safe but limited manner. There is particular interest in using cells derived from the patient to avoid rejection of the transplants by the patient’s immune system. Recent studies have shown that an infusion of inosine (a naturally occurring substance that is similar to adenosine) can improve axonal regeneration and prevent neuronal death. The purpose of this clinical trial is to evaluate the effect of combining transplants of autologous (derived from the patient) Schwann cells (SCs) and Adipose Derived Stromal cells (ADSCs) with an inosine infusion in chronically paralyzed dogs.
Intralesional transplantation of autologous adipose tissue derived stromal cells (ADSCs) and Schwann cells (SCs) combined with infusion of inosine improves motor, sensory and autonomic function of chronically paralyzed dogs.
- Dogs must have suffered a thoracolumbar spinal cord injury at least 3 months previously from which they have failed to recover either motor or sensory function in their hind limbs.
- Dogs with only limited or no motor function in their hind limbs will be admitted – this will be determined at the first evaluation by the investigators.
- Dogs will have to be videotaped when walking on a treadmill and so we can only include dogs that will tolerate working with the investigators on the treadmill.
- Dogs must also be in good health other than their spinal cord injury: dogs with urinary tract infections will not be able to start the study until the infection is treated.
- The owner must be willing to come to the hospital with their dog once a week for the first month of the trial and then once a month for the remainder of the trial.
Phase I: Baseline assessment for 4 weeks
The first step of the project will be for your dog to undergo an evaluation to obtain the baseline data on the neurological status. This evaluation will include: Routine physical and neurological examination, once weekly gait scoring for 4 weeks (This involves walking outside on a non-slip surface for a distance of about 20 feet while we videotape their ability to walk from different angles, and then walking on a treadmill for 15 minutes in three minutes sections, again videotaping them).
Spinal cord assessment and autologous tissue collection
At the end of the baseline assessment, we will image your dog’s spinal cord using MRI and we will assess conduction along the spinal cord using electrophysiological testing. All of this will be performed under general anesthesia at the NCSU Veterinary Teaching Hospital. After the MRI and electrophysiological testing have been performed, an area of hair (approximately 3 inches square) will be clipped on the back of your dog’s neck and the skin will be cleaned thoroughly as for surgery. A two-inch long incision will be made in the skin and a piece of fat (approximately 1 inch square) will be removed for culture of ADSCs. Peripheral sensory nerves located just below the fat will be identified and two pieces approximately one inch in length will be removed to culture SCs. The incision will be closed with sutures and your dog woken up from anesthesia. They should be able to return home the same day but will stay in the hospital overnight if needed. Skin sutures will be removed in 7 – 10 days.
Phase II: Treatment
Your dog will be randomly assigned to one of three treatment groups:
- Group 1: will receive transplanted cells and an inosine infusion
- Group 2: will receive a transplant that contains artificial CSF only
- Group 3: will receive an inosine infusion.
- The minipumps that deliver inosine will be placed under the skin and will be removed again after 2 weeks.
Phase III: Assessment of recovery for 6 months
We will recheck your dog once a month for six months after treatment. This evaluation will include:
- Routine physical examination
- Routine neurological examination.
- Gait scoring when walking outside on a non-slip surface for a distance of about 20 feet and on a treadmill as before.
- At 6 months after the transplantation surgery the MRI of the spine and spinal cord conduction will be repeated.
We will also ask you to fill out a questionnaire at each recheck describing changes you have seen in your dog’s continence and ability to stand and walk.
When your dog has completed the study, we will determine which treatment group they were in, and if they were in group 2 or 3, and did not receive transplanted cells, we can perform the cell transplantations as described at no cost to you if you would like.
Frequently Asked Questions
What are the benefits of enrolling my dog?
If the study hypothesis is correct, it is possible that your dog will show an improvement in hind limb and bladder function as a result of the treatment. Your dog will take part in one of the first controlled clinical trials in dogs that might identify an effective cellular transplantation therapy for paralysis. This information will benefit future dogs with spinal cord injuries and the information generated may also be useful for treatment of people with spinal cord injuries.
Are there any risks to my dog?
Anesthetics: Your dog will be anesthetized in the course of this study. General anesthesia always carries risk of harm, even death. This risk is increased in animals that are unhealthy and we will perform complete physical examinations and routine blood work to identify factors that would increase the anesthetic risk.
Inosine minipump: The minipumps we are using to deliver the inosine have been used widely in mammals to deliver drugs in a constant fashion and have been shown to be safe and effective. However, whenever an implant is placed there is risk of infection. We will take all the normal precautions to ensure sterility during surgery and minimize the change of infection. We will explain the signs of infection to you and if one does occur, we will remove the implant immediately. In the unlikely event that a serious antibiotic resistant infection were to occur, this could have serious consequences to your pet and even be fatal. The substance being infused, inosine, is a food supplement that actually occurs naturally in the body and is not known to have side effects.
Cellular transplantation: Cellular transplantation has also been shown to be safe in experimental models and clinical patients but again, there is a risk of infection as we are introducing something new to the body. Another concern of transplanting stem cells is the risk of them growing out of control and causing a tumor at the site of transplantation, potentially resulting in further neurological deterioration. This phenomenon has only been associated with stem cells generated from embryos and fetuses, not stem cells grown from adult tissues and is considered extremely unlikely to occur.
Neuropathic pain or allodynia: With any intervention in a patient with a spinal cord injury, there is concern that abnormal growth of sensory fibers might ensue and cause a painful sensation (neuropathic pain or allodynia) that could be difficult to treat. This has not been reported in two previous studies of transplantation in dogs with spinal cord injuries.
It is possible that the treatments will not have any beneficial effect and you and your pet will have spent a lot of time and emotional effort without seeing a neurological improvement.
What are my responsibilities if I elect to enroll my dog in this study?
Owner responsibilities include:
- Coming to the hospital once a week with your dog for 4 weeks in phase 1 of the trial
- Coming to the hospital once a month with your dog for 6 months in phase 3 of the trial
- Completing a questionnaire every visit during phase 1 and phase 3 of the trial.
If I have some questions, who should I call?
The principal investigator for this study is Natasha Olby, VetMB, PhD, DACVIM (Neurology) and the research fellow is Ji-Hey Lim, DVM, PhD. They are based at North Carolina State University. If you have questions about the study, please contact the Neurology Laboratory at 919-513-7235 to leave a message or email: firstname.lastname@example.org. You will receive a reply as soon as possible, but delays may be experienced dependent on personnel availability. Please keep in mind they will be unable to answer specific questions about the ongoing care of your pet. These questions should instead be referred to your neurosurgeon.