After someone experiences a spinal cord injury, doctors set off on a race against the clock. Within a few hours, they rush patients into surgery and administer anti-inflammatory drugs, ranging from over-the-counter medications like Advil to the steroid methylprednisolone, to avoid as much damage as possible — keeping in mind that post-injury swelling and insufficient blood supply can wreak further damage on neurons. After intervening during this narrow window of time, scientists have long thought that the chances of additional recovery grow slim.
“The dominant thinking was that you should focus on acute injuries,” Aileen Anderson, a stem cell researcher at the University of California, Irvine, tells Inverse. “If you could just hit a magic bullet at that stage and minimize the amount of damage that’s happening because it kind of rolls out over days and a couple of weeks … this was the place to target.”
But in recent years, labs have made major strides in innovative techniques that can be applied long after the initial damage to the spinal cord, including using electrical currents to re-awaken key pathways in the nervous system and surgeries that could coax injuries to repair themselves.
These methods expand the possibilities of recovery for people who have lived with severe spinal cord injuries for years — even several decades — and may spend up to millions of dollars over their lifetimes on medical care and living expenses, according to the National Spinal Cord Injury Statistical Center.
“The economic impact and the human impact is enormous.”
The leading causes of spinal cord injuries in the U.S. include traffic accidents, falls, and sports-related injuries, a 2016 study found. Each year, they occur among a relatively small number of people — around 17,000. But a large population lives with the residual damage from chronic injuries (estimates vary widely between 250,000 and 1 million people, Anderson says.)
Ultimately, even minor progress for those with chronic injuries could have significant benefits, Michael Fehlings, a neurosurgeon at Toronto Western Hospital in Canada, tells Inverse. The type of full-body paralysis experienced by the late Superman actor Christopher Reeve, for example, can run someone between $10 and $20 million when you factor in costs like multiple caregivers, an electric wheelchair, and home upgrades.
“If one had a treatment that could even partially restore hand and upper extremity function and partially restore independence of a person, the economic impact and the human impact is enormous,” Fehlings says.
A costly injury
The spinal cord is a long, fragile column that contains nerve cells and skinny fibers called axons, which deliver messages back and forth between the brain and nerves located throughout the body. This constant communication tells muscles to move, helps us feel pain, and regulates heart rate, among other crucial functions.
Injuries can impair connections between nerves and hinder the nervous system’s circuitry. For example, these disruptions may cause uncontrolled movements or loss of movement in certain body parts.
An individual’s specific symptoms depend on the location of the injury; for example, impacts higher up in the spinal cord may cause paralysis in most of the body, referred to as quadriplegia or tetraplegia, according to the National Institutes of Health. Damage that occurs lower on the spinal cord can cause paralysis of the legs and lower body, or paraplegia.
Early interventions — including surgery to decompress the spinal cord and drugs that reduce inflammation — have long been considered key to recovery, Fehlings says. Researchers have also looked into techniques like inducing hypothermia in spinal cord injury patients. But ultimately, many efforts beyond surgery have produced only modest results in studies, according to Anderson.
“There were a ton of strategies that people worked on in the lab … to just minimize the initial damage, but there were also any number of failed clinical trials that came out of that,” she says.
Few long-term options
At the moment, patients can find some relief from side effects like muscle spasms and impaired bladder control. But most of what’s currently offered in clinics can’t actually fix the damage underlying these symptoms.
“There are no therapies that recover people with chronic spinal cord injury right now,” Susan Harkema, associate director of the Kentucky Spinal Cord Injury Research Center, tells Inverse. “Most therapies that are approved with a clinical indication are to treat symptoms.”
These therapies include a type of rehab called locomotor training that was pioneered by Harkema and her colleagues at the University of Louisville. During a rehab session, patients can wear a harness for support while a robot or staff member moves their legs on a treadmill. But a small number of centers offer this type of rehab, Anderson adds.
(In 2016, Harkema’s team lost federal funding for a study on locomotor training due to concerns from the National Institute on Disability, Independent Living and Rehabilitation Research that the team strayed from research protocols — an unusual move from a government agency. Later, an internal audit from the University of Louisville failed to find major issues with the study but noted that some aspects of the research could be improved.)
Patients can also receive a technique first developed in the 1960s called electrical stimulation. This method sends low levels of electrical current to the spinal cord through electrodes placed on the skin or implanted near the spinal cord. These devices aim to replicate how the brain typically sends signals to various parts of the body, potentially reviving movement in areas affected by the injury.
“Even when people have a very severe injury, there are some circuits that remain in the nervous system,” Fehlings says. “So the rationale for using the electrical stimulation is to try to, if you will, ‘trick’ the nervous system to try to activate some of these circuits.”
“This is an exciting approach.”
Electrical stimulation has shown benefits, like restoring a degree of arm and leg movement, aiding in the functioning of the lower urinary tract, and improving the effectiveness of rehab. In fact, when combined with rigorous physical training, it has even helped people walk again by engaging nerves that control lower-body movement.
While that’s likely not possible for people with full-body paralysis due to the degree of damage, electrical stimulation may still help achieve a degree of movement that wouldn’t otherwise be possible, such as improved hand grip and strength.
“If we stimulate the spinal cord itself, people can move voluntarily who are fully paralyzed, even up to 40 years post-injury,” Harkema says.
Over the last few years, the U.S. Food and Drug Administration has approved a handful of electrical stimulation devices, including Abbott’s Proclaim Plus device and Saluda’s Evoke System.
Moving forward, scientists want to pinpoint the precise group of neurons behind stimulation’s success so that they can be more effectively targeted during the process.
Some labs are even working on high-tech clothing that includes electrodes to help people on the go without the need for surgical implants — a potentially crucial breakthrough since real-time stimulation gives people a higher degree of mobility. Eventually, the goal is for people to move without requiring stimulation.
“This is an exciting approach,” Fehlings says. “It’s not a cure for spinal cord injury — it needs to be validated in larger clinical trials — but it’s something that does have potential hope for individuals who have a chronic spinal cord injury.”
Radical regrowth
In what is perhaps the most revolutionary proposal, some scientists want to transplant stem cells into the spinal cord to restore sensory and motor function. This method has shown promise in animal studies, and several phase 2 human clinical trials are in the works.
The hope is that the new cells can replace the ones lost to injury and repair the spinal cord’s signaling highway. Plus, future transplants could use stem cells derived from the patient’s own body, potentially avoiding the negative health impacts of transplant rejection, Anderson explains.
“I’m extremely hopeful.”
Above all, this option could help patients who lack enough viable neural cells to benefit from other therapies that are currently in use.
“The cellular transplantation approach seeks to address the individuals who have such a devastating spinal cord injury that even electrical stimulation is just not going to work,” Fehlings says.
Some teams, including Anderson and her colleagues, are also trying to put specialized materials into people’s spinal cords, such as scaffolds made of hydrogels, as another method to help the spinal cord reconnect itself. It could also help to combine scaffolding and stem cells, Anderson says, an idea currently in the early stages of development.
Future hurdles
Even if some of these approaches prove to be effective in trials, a lack of funding could prevent them from reaching wide swaths of patients. Since the number of spinal cord injuries that occur every year is relatively tiny, pharmaceutical companies may not see these concepts as worthwhile investments.
But these injuries share many features with conditions that also affect the central nervous system, such as multiple sclerosis, strokes, and traumatic brain injuries.
“We hope that [with] what we develop for spinal cord injury, we can make the case that it might be able to impact this broader set of diseases and therefore it’s worth investing in,” she says.
Despite looming challenges, Fehling says he’s feeling optimistic that regenerative medicine approaches like stem cell transplants could arrive in clinics within the next five to 10 years. If so, it could transform the lives of patients who may not benefit from today’s options.
“We’re at an inflection point in the regenerative medicine era,” he says. “I’m extremely hopeful.”
