A Phase 1 clinical trial of GGF2 in dogs with disc-induced acute spinal cord injuries
*No longer recruiting*
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 in rodents suggest that Glial Growth Factor 2 (GGF2) improves the recovery from a spinal cord injury. The purpose of this clinical trial is to evaluate the safety of GGF2 in dogs with severe spinal cord injuries due to acute intervertebral disc herniations.
What is GGF2?
GGF2, also known as neuroregulin 1, is a growth factor that has many effects in the body, one of which is to support the growth and survival of oligodendrocytes, cells within the central nervous system (the brain and spinal cord) that produce myelin, a fatty substance that enhances conduction of impulses in the nervous system. When given to rodents with spinal cord injuries, it increases the survival of oligodendrocytes, and this in turn is associated with improved recovery of hind limb function. There is a lot of interest in this growth factor for its potential to treat a variety of different human diseases, and it is currently in clinical trials as a treatment for people with heart failure.
In order to qualify for the study your dog must have suffered a severe thoracolumbar spinal cord injury due to an acute disc herniation. The injury must be severe enough to cause paralysis of the hind legs and loss of sensation in their hind feet, and it must be recent: they can only be included if they have been unable to walk for 48 hours or less. We will assess their recovery very closely, so they must be amenable to regular handling and walking on a treadmill. Aggressive dogs will be excluded. They must also be in good health other than their spinal cord injury. They should not have been treated with a human recombinant protein previously as this might cause them to have a hypersensitivity response to GGF2, and they should not have a history of an immune mediated disease (for example, immune mediated hemolytic anemia or thrombocytopenia).
This phase I trial will evaluate the safety of GGF2 in dogs with naturally occurring spinal cord injury as a result of acute disc herniation. The standard treatment will take place as usual. In this trial the dogs will be hospitalized for 7 days following surgery to receive daily subcutaneous doses of GGF2 or placebo. They will then be discharged to their owners and re-evaluated at 2, 4, 6, and 8 weeks postoperatively with an MRI performed at 8 weeks.
Frequently Asked Questions:
What are the benefits of enrolling my dog?
- In return for participating in this study, the study will pay $3000 towards the cost of diagnosis and surgical treatment of your dogs spinal cord injury, will pay for the 7 days of hospitalization while the GGF2 is being administered, and will cover the cost of the scheduled rechecks and the MRI at the end of the study.
- If your dog receives GGF2, it is possible that your dog will show an improvement in hind limb and bladder function as a result of the treatment.
Are there risks for my dog?
GGF2 has not been administered to dogs with spinal cord injuries, and so it is possible there it will cause an unanticipated adverse event that could even be fatal. GGF2 is a human recombinant protein, and the adverse event that is most likely is an abnormal immune response to the protein. In initial work, we determined the tolerability of GGF2 in healthy dogs. In a first round of testing we looked at 2 different doses, and we found that higher doses can cause pain at the site of the injection (which responded rapidly to treatment with an anti-inflammatory drug). The dose that we are using in this protocol is much less likely to cause any pain and we will assess each patient carefully for this complication and treat it if it appears. We also found that if we repeated dosing after an interval of a month, we caused a hypersensitivity reaction and dogs developed transient signs of brain dysfunction (tremors and a wobbly gait). These signs resolved with no treatment. To ensure that this response was only caused by repeating the dosing, we tested GGF2 using the 7 days dosing regimen to be used in the study and monitored dogs for 3 months. None of them developed this adverse response and so we feel comfortable moving to testing its tolerability in dogs with spinal cord injuries. However, we are excluding dogs with a known history of abnormal immune responses for this reason.
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?
If you decide to take part in this study the total duration of participation is 2 months; they will remain in the Veterinary Teaching Hospital for 7 days at the start of the trial. The rest of the time they will be at home with you, with regular rechecks at the hospital.
Clients will be responsible for exam fees for patients that do not qualify for the study.
If you have an acutely paralyzed dog eligible for the study, please contact the Neurology Service at 919-513-6692 or the ER after hours at 919-513-6911
Natasha Olby, Vet MB, PhD, Dip ACVIM (Neurology) Associate Professor of Neurology/Neurosurgery at North Carolina State University College of Veterinary Medicine