The cells themselves help, and the protein they make helps.
In the long struggle against ALS — a disease that dismantles the body's ability to move, speak, and breathe — researchers at Cedars-Sinai have reached a quiet but significant threshold: eighteen patients received engineered stem cells directly into their spinal cords, and none were seriously harmed. The cells survived, continued producing a neuroprotective protein called GDNF, and in some cases persisted for more than three years. It is not a cure, nor a claim of victory, but in a disease defined by relentless loss, the confirmation that a new path is safe enough to walk is itself a form of progress.
- ALS offers no cure and no reprieve — motor neurons die, muscles fail, and the body's most basic functions erode in sequence.
- For decades, GDNF has been known to protect dying motor neurons, but the blood-brain barrier has made delivery nearly impossible — until now.
- Cedars-Sinai engineers solved the delivery problem by turning stem cells into living factories, transplanting them directly into the spinal cord to produce GDNF from within.
- The trial's elegant design — treating only one side of the spinal cord and comparing it to the untreated side — confirmed safety, but also exposed complications: cells migrating into sensory regions and benign growths at transplant sites.
- Researchers are already refining the approach, targeting earlier-stage patients and more precise surgical placement, while a second trial extends the method to the motor cortex of the brain.
Eighteen ALS patients received injections of engineered stem cells into their spinal cords at Cedars-Sinai Medical Center. None developed serious side effects. In a disease with no cure and no mercy, the absence of harm is itself a milestone.
ALS destroys motor neurons — the cells that carry movement signals from brain to muscle — leaving patients progressively unable to move, speak, or breathe. A protein called GDNF has long been known to protect these neurons, but the blood-brain barrier prevents it from reaching them. The Cedars-Sinai team, led by Clive Svendsen, bypassed this obstacle by engineering stem cells to produce GDNF directly inside the spinal cord. Once transplanted, these cells serve a dual purpose: they become supportive glial cells that stabilize surrounding neurons, and they continuously release the protective protein.
The trial used the body's own symmetry as a control — injecting cells into only one side of the spinal cord and comparing the treated leg to the untreated one. The transplanted cells survived, kept producing GDNF, and in some patients persisted for more than three years without damaging the treated side. But complications emerged: in some patients, cells migrated higher than intended into sensory regions, potentially triggering pain; in others, benign growths appeared at the transplant site.
These are problems of precision, not principle — the kind that better surgical targeting can address. The next phase will treat patients earlier in the disease and aim for lower spinal cord regions where more motor function remains to be preserved. A second trial, targeting the motor cortex in the brain, has already begun. The researchers are not claiming a breakthrough. They are claiming something more durable: proof that the approach is safe, that the cells can survive in the human body, and that the work is worth continuing.
Eighteen patients with ALS walked into Cedars-Sinai Medical Center and received an injection of engineered stem cells into their spinal cords. None of them developed serious side effects. That simple fact—the absence of harm—marks a threshold in the treatment of a disease that has no cure and no mercy.
Amyotrophic lateral sclerosis kills motor neurons, the cells that carry signals from the brain down the spine to muscles. Without them, the body gradually loses the ability to move, to speak, to breathe. It is relentless and progressive. For decades, researchers have known that a protein called GDNF could theoretically protect these dying neurons. The problem was getting it there. The blood-brain barrier, the body's own security system, blocks most molecules from entering the central nervous system. GDNF cannot cross it on its own.
The Cedars-Sinai team, led by Clive Svendsen, found a workaround: use stem cells as delivery vehicles. They engineered cells to produce GDNF directly in the spinal cord, where the motor neurons live. When transplanted, these cells do two things at once. They transform into new supportive glial cells—the scaffolding that holds neurons in place. And they continuously release the protective protein. It is, as one researcher described it, a double approach: the cells themselves help, and the protein they make helps.
The trial was designed with elegant simplicity. Because ALS typically weakens both legs at roughly the same rate, the surgeons injected the engineered cells into only one side of the spinal cord. This created a built-in control. They could measure the treated leg against the untreated leg and see if the therapy made any difference—or caused any harm. After one year of follow-up, the answer was clear: the transplanted cells did not damage the treated leg. The cells survived. They kept producing GDNF. Some of them persisted for more than three years.
But the trial also revealed complications that will need solving. In some patients, the injected cells migrated higher than intended, ending up in sensory regions of the spinal cord where they may have triggered pain. In others, benign growths appeared at the transplant site. These are not catastrophic findings—they are the kind of problems that surgeons and engineers can address with better targeting and refined technique. The next phase will aim lower in the spinal cord and will enroll patients earlier in the disease, when there is more motor neuron function to preserve.
The research was published in Nature Medicine in September 2022. Cedars-Sinai has already begun a second trial, this one targeting the motor cortex—the brain region that initiates movement in the hands. The first of sixteen patients in that study has been treated. The researchers are not claiming victory. They are claiming something more modest and more honest: proof that this approach is safe enough to continue, that the cells can survive in the human body, and that they can do their job. In a disease where the only certainty is decline, that is a foothold.
Notable Quotes
We were able to show that the engineered stem cell product can be safely transplanted in the human spinal cord. And after a one-time treatment, these cells can survive and produce an important protein for over three years that is known to protect motor neurons that die in ALS.— Clive Svendsen, senior author and executive director of Cedars-Sinai Regenerative Medicine Institute
We're excited that we proved safety of this approach, but we need more patients to really evaluate efficacy, which is part of the next phase of the study.— J. Patrick Johnson, co-lead author and co-medical director of Spine Center at Cedars-Sinai
The Hearth Conversation Another angle on the story
Why does it matter that the cells survived for three years? Couldn't they have just worked for a few months and then stopped?
Because ALS is a slow disease. You don't lose all your function overnight. If the cells only worked for a few months, you'd need repeated surgeries, repeated transplants. Three years of function from a single injection means you might actually change the trajectory of someone's life—buy them time, preserve what they have.
The article mentions pain in some patients. How serious is that?
It's a real problem, but it's a targeting problem, not a fundamental flaw. The cells went to the wrong neighborhood in the spinal cord. Better imaging, better surgical technique—that's fixable. It's not like the cells themselves were toxic.
Why inject only one side of the spinal cord?
It's the only way to know if the therapy actually works. If you treat both sides, how do you know which changes are from the treatment and which are just the natural progression of the disease? By leaving one side untreated, you have a comparison built right into the patient's own body.
What happens to these patients now? Are they cured?
No. The therapy slowed nothing down in this trial—the goal was just safety. But the cells are there, producing protein, protecting neurons. The next trials will try to measure whether that protection actually slows the disease. That's the real test.
Why start a second trial in the brain instead of refining the first one?
Because ALS affects different regions. The spinal cord controls legs and trunk. The motor cortex controls hands and arms. If this works in one place, it might work in others. And they're learning as they go—the brain trial is also a chance to refine the technique before expanding the spinal cord work.