Only hours after a traumatic spinal cord injury, when the life-and-death moments have passed and ongoing challenges are just coming into focus, some patients are receiving an experimental drug that may change their lives.
The investigational medication, called SUN13837, is given intravenously within 12 hours of a traumatic spinal cord injury (SCI) and then daily for 28 days. It is a fat-soluble molecule that may protect damaged neurons and even promote new nerve growth, preventing some loss of function.
Shepherd Center was one of the first rehabilitation centers in the country to launch a clinical trial to test the safety and effectiveness of SUN13837, which was developed by the Japanese pharmaceutical company Asubio. The first Shepherd Center patient was enrolled in 2013 in a partnership with Grady Memorial Hospital in Atlanta. Asubio is seeking to enroll 164 patients at more than 60 acute trauma centers around the country and internationally.
“When someone has a spinal cord injury, the first thing they want to know is, ‘What can we do to decrease the damage or disability?’” said Michelle Tidwell, RN, BSN, clinical study coordinator at Shepherd Center’s Virginia C. Crawford Research Institute. “There’s so little out there for spinal cord injury. Having this trial is very important.”
A cascade of bodily reactions occurs when the spinal cord is injured. Restricted blood flow, inflammation and a flood of neurotransmitters contribute to the irreversible death of nerve cells. Researchers have long sought a way to prevent damage and trigger nerve regeneration. Stem cell therapies offer promise, but even beyond the controversy involving embryonic stem cell research, the treatments have some downsides. Beta fibroblastic growth factor, a protein found in stem cells, can trigger too much cell growth.
The investigational SUN13837 mimics the properties of the beta fibroblastic growth factor, keeping neurons alive and healthy and promoting the regrowth of nerve axons, or the long, delicate fibers that relay nerve messages – without harmful cell growth.
This is not being touted as the elusive “cure” for spinal cord injury. But SUN13837 may significantly improve functioning in SCI patients, said Issi Clesson, RN, MSCN, CCRP, Shepherd Center’s director of clinical research.
For example, an injury at cervical level 4 (C-4) affects the biceps, so with a complete injury, the patient can’t move his arms and is dependent upon others for care. But if the impairment begins at C- 6 level, the patient often retains movement in the biceps and wrists. “He can operate his own wheelchair, feed himself and meet many of his daily needs with little support from a caregiver,” Clesson explained. “Improvement in two motor levels means significant improvement in function and lifestyle.”
Animal studies revealed SUN 13837 led to improved locomotor scores. The mechanism of action wasn’t clear, but it may involve neuroprotection at the injury site, regeneration at the injury site or neural plasticity below the level of spinal cord injury – the ability to create new neural pathways. Phase I clinical trials also demonstrated that SUN13837 did not cause harmful side effects in healthy people.
In the Phase II trial, patients randomly receive either SUN13837 or a placebo, an inactive substance. To participate in the study, patients must have cervical injuries – levels C-4 to C-7 – that are complete or incomplete (A, B or C on the American Spinal Injury Association (ASIA) Impairment Scale). People with certain medical conditions, such as a cardiac condition, brain injury or trauma that requires prolonged surgery, are not eligible for participation.
Patients will be considered a “responder” to the medication if they improve by two or more motor function levels on either their right or left side, according to the International Standards for Neurological Classification of Spinal Cord Injury Scale. Researchers also hope to learn more about how the drug works.
“Cautious optimism is needed until this and other studies are conducted,” Clesson said. “But there is hope that this may open new doors for future research and for those with acute SCI.”
Many patients with spinal cord injury would welcome the chance to have an experimental treatment, but the logistics of this research study are challenging. Patients must be identified at a trauma center and given the first doses promptly, then receive their ongoing therapy and medication at a rehabilitation center. The study tracks patient progress with periodic clinical evaluations over six months.
A partnership with neurosurgeon Nick Boulis, M.D., of Emory University has made this coordination of care possible. The collaboration brings Shepherd Center together with Grady Hospital’s neurotrauma and emergency room resources, as well as Emory University’s translational spinal cord regenerative medicine program.
At Shepherd Center, the team is led by David F. Apple, M.D., medical director emeritus, and Tidwell. Diane Johnston, MSPT, spinal cord injury program education coordinator, performs most of the assessments and trains other evaluators around the country, with the help of Shari McDowell, PT, DPT, director of the Spinal Cord Injury Program.
Building bridges of communication between trauma centers and rehabilitation facilities has been a side benefit of the study.
“A good working relationship is crucial to the success of the clinical trial,” Clesson noted. “Shepherd has admissions liaisons at Grady almost full time who can facilitate the evaluation and transfer process.”
Patients understand they may be receiving a placebo, rather than the experimental treatment. But they are still enthusiastic about participating in the study, she says.
“They see this as a gift or opportunity to give back to someone else who has a similar injury,” Johnston said. “Whether it helps them or not, they see the bigger picture that it may help others after them. It’s an incredible thing they’re doing for research and for potential recovery in the future for those with spinal cord injury.”
For more information on Shepherd Center research, click here.
By Michele Cohen Marill