Stem Cell Trials
Chris Barr woke up in hospital, paralyzed from the neck down. He is now walking without assistance, thanks to advances in stem cell treatment.
Chris was surfing at Ocean Beach, San Francisco, as he did each weekend for the past ten years. Except this time, he fell and broke his neck in eight places. When his family came to see him, he asked them to switch off the ventilator keeping him alive.
Dr. Mohamad Bydon, a neurosurgeon at Mayo Clinic made contact with the Barr family and Chris became the first patient for a stem cell transplant trial. Stem cells were taken from Chris’s belly fat and injected into his spinal cord. Chris began to hit small milestones, like tying his shoes, but to the surprise of many, he was able to walk with assistance six months after the injections. Two years after his injury and 12 months following injection, Chris was able to stand and walk on his own.
Dr. Bydon is quick to note that responses may range—two of the ten trial patients did not respond to the treatment and others varied in their progress. Phase two of the trial, with 40 new patients, will begin later this year (2020).
This is welcome news for many who suffer spinal injuries, particularly patients with myelomalacia. Researchers are excited, as the prognosis for spinal cord injury recovery has traditionally been grim.
Myelomalacia is the softening of the spinal cord, resulting from injury and insufficient blood supply to the spinal cord. Myelomalacia can cause loss of motor function in your hands or feet, jerking of your limbs, numbness, difficulty breathing, and can be fatal if it causes paralysis of the respiratory system. Myelomalacia can also lead to neurological problems.
In another stem cell clinical trial, Kristopher Boesen regained movement in his arms and hands after being paralyzed from the neck down in a car accident. Kristopher had difficulty breathing on his own due to his injuries and was told he may never be able to regain control of his limbs again.
Instead of the standard surgery offered for spinal cord injury (that would stabilize the spine, but likely do little for motor and sensory functions), Kristopher enrolled in a clinical trial led by Dr. Edward D. Wirth III, chief medical director of Asterias Biotherapeutics.
The trial used injections of AST-OPC1, an agent consisting of oligodendrocyte progenitor cells (OPCs) deriving from embryonic stem cells found in the brain and the spinal cord. OPCs are the myelin-forming cells of the brain and spinal cord that help nerve cells to function. Researchers aimed to reduce the size of the injury cavity, replace the myelin coating of the nerve cells, stimulate nerve cell growth, and produce blood vessels directing oxygen to the injured site.
The clinical trial is now at the 10 million cell level, which is the amount found to be most effective in the pre-clinical studies. Keck Medical Center is one of the 6 sites in the United States authorized to enroll subjects and administer the clinical trial dosage.
Spinal Cord Stimulation Trials
Epidural spinal cord stimulation has shown promising results, according to a trial by the University of Minnesota. The first two patients were women with severe myelomalacia and syringomyelia with T8 and T4 lesions, 11 and 5 years out from the initial injury.
The doctors thought the stimulation would fail because of the severity of the myelomalacia and almost transected cords. But the women regained voluntary movement, bladder and bowel control, and even orgasmic functioning.
The electrical stimulation is not directed to the site of the lesion but to a segment of the cord. For example, a patient with a T4 lesion may have electrodes implanted at T11. Researchers explain there are “intact super spinal connections” that still survive and pass through the spinal cord lesion. The stimulation floods the sensory system, removing the synaptic plasticity in the inner neurons which then activates the few fibers.
The study enrolls adults with thoracic SCI between C6 and T10. All patients are American Spinal Injury Association Impairment Scale A or B with full arm strength, intact segmental reflexes below the lesion of injury, and no lower motor neuron injury, and had to be at least 1 year post-SCI. Patients were also screened for cardiovascular dysautonomia; those with dysautonomia took periodic autonomic tests.
The two women were implanted with spinal cord stimulators; lower-extremity volitional movement was demonstrated by both patients during functional lower-leg exercises assessed by surface electromyography (EMG) in stimulated and non-stimulated modes.
Statistically significant changes were further observed across all muscle groups, as were improvements in bladder, bowel, and sexual function. Patients had a return of “synergy” (urination preceding defecation); patient 1 experienced a reduction in urinary incontinence, while patient 2 achieved volitional urination and was able to empty her bladder up to 100ml on command. In both patients, bowel time was reduced from about 90 minutes to 30 minutes. The most significant finding was restoration of orgasm with sexual intercourse in patient 2.
Patient 2 also experienced a reversal in orthostatic hypotension during tilt testing. Both patients saw improvement in cardiovascular autonomic function when targeting the right centers, and no alterations to normal cardiovascular function were found in patients with dysautonomia.
Dr. David Darrow, who was involved in the trial, Dr. David Darrow explains the origins of the research: “It’s been about 10 years since the serendipitous discovery that if you apply spinal cord stimulation below their lesion, patients with thoracic paraplegia can regain some ability to control their legs, despite not having moved them in up to 4 years.”
He further noted that, “the important thing is that our study was in severe patients [i.e., furthest out from their injury]. It shows that age or time since injury should not preclude this therapy.”