People once dependent on wheelchairs after having a stroke are walking again since receiving injections of stem cells into their brains. Participants in the small trial also saw improvements in their speech and arm movements.
“One 71-year-old woman could only move her left thumb at the start of the trial,” says Gary Steinberg, a neurosurgeon at Stanford University who performed the procedure on some of the 18 participants. “She can now walk and lift her arm above her head.”
Run by SanBio of Mountain View, California, this trial is the second to test whether stem cell injections into patients’ brains can help ease disabilities resulting from stroke. Patients in the first, carried out by UK company ReNeuron, also showed measurable reductions in disability a year after receiving their injections and beyond.
All patients in the latest trial showed improvements. Their scores on a 100-point scale for evaluating mobility – with 100 being completely mobile – improved on average by 11.4 points, a margin considered to be clinically meaningful for patients. “The most dramatic improvements were in strength, coordination, ability to walk, the ability to use hands and the ability to communicate, especially in those whose speech had been damaged by the stroke,” says Steinberg.
In both trials, improvements in patients’ mobility had plateaued since having had strokes between six months and three years previously.
“We used to think the affected brain circuits were dead,” says Steinberg. “Now, we have to rethink this, and I personally think the circuits are inhibited, and our treatment helps to disinhibit them.”
Steinberg injected the cells through a borehole in the skull into regions of the brain that control motor movements, and which had been damaged by the stroke. Each participant received either 2.5, 5 or 10 million cells.
The injected material consisted of mesenchymal stem cells taken from the bone marrow of two healthy donors. SanBio genetically engineered the cells to possess a gene called Notch1, which activates factors that help brain development in infants. Experiments in rats revealed that the engineered stem cells disappear within a month or so, but not before secreting several growth factors that build connections between brain cells and spawn the growth of new blood vessels to nourish growing brain tissue.
“We think the cells change the adult brain so that it’s more like a baby’s brain, which repairs very well,” says Steinberg. “They are secreting all sorts of growth factors, which aid repair, and which also alter the immune system to get rid of inflammation that otherwise obstructs repair.”
In the ReNeuron trial, patients received neural stem cells originally extracted from the brains of aborted fetuses, then multiplied to produce larger amounts.
“This is very encouraging news for the field of stem cell research and especially patients with established disability as a result of stroke, where this is no proven treatment to aid recovery,” says Julian Howell, chief medical officer at ReNeuron. “Both companies are at a similar stage of development, and while it’s great to hear stories of major improvements in some patients, controlled studies are absolutely necessary to establish the benefits and risks of stem cell therapy for stroke.”
ReNeuron is preparing a second trial, while SanBio is in the process of performing the treatment on a further 156 patients. Steinberg says that this time, a third of the patients will receive a sham treatment – a hole in the head without the injection of stem cells – and the remainder will receive either 2.5 or 5-million cells.
There are around 30 similar trials in progress. These deliver stem cells to stroke patients by injecting them into the blood, but none have shown such remarkable results as the two trials that injected the cells into the brain, says Steinberg. “We still have much to learn, including the right cell for the job, the right dose and the right means of delivery,” he says.
The UK Stroke Association welcomed the results but also cautioned that further trials are essential to provide additional evidence the treatment works. “Although small, this latest trial suggests that the treatment is safe and may be able to restore movement to people previously lost after stroke,” says Shamim Quadir, a spokesman for the association. “The trial adds to a growing body of early clinical evidence suggesting stem cell treatment could promote recovery in people months, even years, after having a stroke, bringing hope to many living with a disability.”
Author: Andy Coghlan