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A paralyzed Superman rose from a wheelchair and walked, during a 2000 Super Bowl commercial. The advertisement drew criticism, because, to some, it promised false hope.
The ad’s star, Christopher Reeve — famous for playing the caped superhero in a series of movies — was rendered quadriplegic in a 1995 horse-riding accident. The actor turned activist pushed for more research funding in general, and an end to a ban on embryonic stem cell research in particular.
Reeve, who died in 2004, would likely be pleased with research’s path to paralysis treatment. Activity has intensified over the past decade or so, with some recent notable milestones. Multiple approaches now hold promise — including implants, stem cells, and molecular therapies.
The concept of using devices connected to the brain to restore function through an electric signal goes back to 1780, when Italian scientist Luigi Galvani linked a frog’s brain to a leg muscle with an electrical wire. In 1996, electrodes implanted into a man’s brain allowed him to control a computer cursor with his thoughts. In 2005, a similar approach enabled a paralyzed patient to control a robot arm.
Efforts to restore a break in the nervous system’s neurological wiring with actual, physical wires have since become less crude and more specific. In 2018, a so-called “pacemaker for the brain” was implanted in a patient. This device differentiated itself from its predecessors by sending more targeted stimulations to more specific muscles.
The devices continue to get smaller and more specific. The latest wrinkle involves adding machine learning to the mix, so the device can teach newly linked muscles and neurons how to work together again. In 2023, a Swiss group led by neuroscientist Gregoire Courtine, implanted what he calls a digital bridge — essentially a set of electrodes between brain and body — to help a paralyzed Swiss man regain some mobility.
Just a few months ago, Elon Musk’s Neuralink announced it had implanted a chip that restored some of a patient’s vision and mobility. Company material says the chip works by essentially redirecting electric signals from the brain around damaged areas. However, external scientists have yet to evaluate the technology because the company has not published any of its results in peer-reviewed literature.
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Philip Troyk, a biomedical engineering professor at the Illinois Institute of technology, says that although these approaches are promising, they are still crude compared to the brain’s sophistication.
The nervous system works with both electrical and biochemical signals. Dealing with both is a “very, very complicated problem,” Troyk says.
Despite the brain’s complexity, many scientists have essentially treated it as a primitive digital computer. Functionally, they are working with the concept that each neuron is either “on” or “off” — the digital equivalent of a one or a zero. That doesn’t account for subtle variations in, or degrees of voltage. Nor does it consider neural transmitters, which are chemical, not electrical in nature.
Troyk and his team are grappling with this complexity by implanting 25 tiny modules — each 5 mm wide and 1 mm thick. Each module contains 16 electrodes. And there’s no wires, because they communicate externally with the same kind of technology used for a wireless cell phone charger.
So far, they’ve conducted one set of implants as a proof-of-concept study to restore vision and are aiming for another by the end of the year. Although the study is now focusing on vision, the approach could be applied more widely.
As promising as brain implants are, they have limitations. “For many of the brain implants, you have to have sensation in your lower extremities,” says Mohamad Bydon, a Mayo Clinic neurosurgeon. “Patients with spinal cord injury often do not have that.”
And many existing approaches require some kind of connection to an external control source.
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The Holy Grail of regenerative medicine is regrowing cells that are missing or have been damaged. A breakthrough discovery in 1998 showed that this might be possible, when scientists isolated cells from an embryo and showed they were pluripotent — meaning they could grow into many different cell types. That research was initially stymied by a U.S. ban on research from cells obtained from embryos.
Bydon’s group derived stem cells from bone marrow and body fat for an experimental treatment in 10 patients with paralysis. In April 2024, the group reported mixed — but promising — success. About a third showed significant improvement, with at least one patient gaining the ability to walk, says Bydon.
Another third showed some improvement — like the return of some sensations, as well as control over bowel and bladder functions. And a third showed no change.
Bydon is not sure why the approach has shown mixed success. “Why clinical response to the stem cells is happening in some patients and not others, we are continuing to study,” he says.
But Bydon notes that even limited success could have potentially huge quality-of-life implications. For instance, gaining the ability to transfer from bed to a wheelchair would be a massive improvement for a paralyzed patient, even if they were still unable to walk.
The group is now undergoing a larger study that will include up to 40 patients. Bydon intends to refine their approach and understand how to maximize its efficacy. He suspects that the ability to successfully deliver blood supply to the area they are attempting to repair might help.
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One group is trying to use molecular therapy to try to do just that. Cells use a complex series of chemical signals to decide what to do. Gaining control of those signals might provide a way to prevent or minimize scarring — which is a component of paralysis.
A group led by Samuel Stupp, a Northwestern University professor, has developed a molecular approach that has shown promising signs in animals. The technique employs a collection of molecules that form a filament and dance. That motion aids in repair and connectivity, he says. Although this method has not yet been tested in humans, Stupp hopes to initiate such studies this year.
While experimental approaches focus on one kind of repair, usually to one specific part of the body, clinical solutions might draw upon several.
“A combination of surgery, stem cells and neural stimulation might be necessary to achieve improvements in outcomes,” says Bydon.
Troyk adds that, although the experimental approaches have shown promise, we are a long way from an overall cure for paralysis.
“It’s important not to destroy hope, but to have a sober, realistic view,” Troyk says.
Although recent experimental steps to treat paralysis have been small and halting, they are nonetheless significant.
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Before joining Discover Magazine, Paul Smaglik spent over 20 years as a science journalist, specializing in U.S. life science policy and global scientific career issues. He began his career in newspapers, but switched to scientific magazines. His work has appeared in publications including Science News, Science, Nature, and Scientific American.